Myalgic encephalomyelitis/chronic fatigue syndrome-an insidious disease:The recent COVID-19 pandemic has brought substantial attention to the overlapping symptoms between long COVID and myalgic encephalomyelitis/chron...Myalgic encephalomyelitis/chronic fatigue syndrome-an insidious disease:The recent COVID-19 pandemic has brought substantial attention to the overlapping symptoms between long COVID and myalgic encephalomyelitis/chronic fatigue syndrome(ME/CFS),a chronic and poorly understood neurological disorder(Shankar et al.,2024).展开更多
Sphingolipids not only exert structural roles in cellular membranes,but also act as signaling molecules in various physiological and pathological processes.A myriad of studies have shown that abnormal levels of sphing...Sphingolipids not only exert structural roles in cellular membranes,but also act as signaling molecules in various physiological and pathological processes.A myriad of studies have shown that abnormal levels of sphingolipids and their metabolic enzymes are associated with a variety of human diseases.Moreover,blood sphingolipids can also be used as biomarkers for disease diagnosis.This review summarizes the biosynthesis,metabolism,and pathological roles of sphingolipids,with emphasis on the biosynthesis of ceramide,the precursor for the biosynthesis of complex sphingolipids with different fatty acyl chains.The possibility of using sphingolipids for disease prediction,diagnosis,and treatment is also discussed.Targeting endogenous ceramides and complex sphingolipids along with their specific fatty acyl chain to promote future drug development will also be discussed.展开更多
Background:The specific impact of sphingolipid metabolism on developing hepatocellular Carcinoma(HCC)remains unclear.This study aims to explore the relationship between sphingolipid metabolism and HCC prognosis,immune ...Background:The specific impact of sphingolipid metabolism on developing hepatocellular Carcinoma(HCC)remains unclear.This study aims to explore the relationship between sphingolipid metabolism and HCC prognosis,immune response,and drug sensitivity.Methods:Data were obtained from The Cancer Genome Atlas(TCGA)-Hepatocellular Carcinoma(LIHC)and Gene Expression Omnibus(GEO,GSE14520 datasets).47 sphingolipid metabolism genes were obtained from the Kyoto Encyclopedia of Genes and Genomes(KEGG)database.After classifying HCC samples using the Non-negative Matrix Factorization(NMF)clustering method,differentially expressed genes were screened.Then,8 risk genes were obtained by univariate analysis,survival random forest reduction and lasso analysis.The expression of 8 risk genes was verified in vitro.Results:8 risk genes were used to construct the Sphingolipid score model.High-Sphingolipid score predicted poor prognosis of HCC patients.Sphingolipid score was associated with immune checkpoints(IL-1B,TLR4,TGFB1,and IL-10),immune cells(Th2,Treg,MDSC,Neutrophil,Fibroblasts and macrophage),and MAPK Cascade.In the High-Sphingolipid score group,a significantly higher proportion of patients with TP53(p53)mutations was significantly higher(56%).Furthermore,patients with a high-Sphingolipid score were predicted to have a higher sensitivity to chemotherapy drugs.In vitro validation showed that compared with normal liver cells LX-2,TRIM47,and S100A9 significantly increased in liver cancer cells Hep G2,MHCC-97H,and Hep3B2.1-7,while SLC1A7,LPCAT1,and CFHR4 significantly decreased.Silencing TRIM47 reduced the proliferation and promoted apoptosis.The levels of ceramide synthesis-related indexes(CERS1,CERS6,CERS5,and SPTLC2)increased,and the ACER3 related to catalytic hydrolysis decreased.Conclusion:We constructed a sphingolipid metabolism-related prognostic signature(Sphingolipid score)based on 8 risk genes.TRIM47 may affect the development of liver cancer by regulating the relevant indicators of ceramide synthesis and catalytic hydrolysis.展开更多
A set of three sphingolipids, N-2′-hydroxyplmitoyl-1-O-β-D-glucopyranosyl-9-methyl-4E, 8E-sphingadiene （A）, N-2′-hydroxyl-3′E-octadecenoyl-1-O-β-D-glucopyranosyl-9-methyl-4E, 8E-sphingediene （B） and N-palmito...A set of three sphingolipids, N-2′-hydroxyplmitoyl-1-O-β-D-glucopyranosyl-9-methyl-4E, 8E-sphingadiene （A）, N-2′-hydroxyl-3′E-octadecenoyl-1-O-β-D-glucopyranosyl-9-methyl-4E, 8E-sphingediene （B） and N-palmitoyldihydrosphingosine （C）, were isolated from two marine-derived mangrove endophytic fungal strains （strains No. 1924 and 3893） from the South China Sea. Their structures were elucidated by 2D NMR and FABMS methods. It is the first time that these sphingolipids were separated and obtained from marine-derived mangrove endophytic fungus from the South China Sea.展开更多
8-Sphingolipid desaturase is the key enzyme that catalyses desaturation at the C8 position of the long-chain base of sphingolipids in higher plants. There have been no previous studies on the genes encoding AS-sphingo...8-Sphingolipid desaturase is the key enzyme that catalyses desaturation at the C8 position of the long-chain base of sphingolipids in higher plants. There have been no previous studies on the genes encoding AS-sphingolipid desaturases in Brassica rapa. In this study, four genes encoding AS-sphingolipid desaturases from B. rapa were isolated and characterised. Phylogenetic analyses indicated that these genes could be divided into two groups： BrD8A, BrD8C and BrD8D in group I, and BrD8B in group II. The two groups of genes diverged before the separation of Arabidopsis and Brassica. Though the four genes shared a high sequence similarity, and their coding desaturases all located in endoplasmic reticulum, they exhibited distinct expression patterns. Heterologous expression in Saccharomyces cerevisiae revealed that BrD8A/B/C/D were functionally diverse AS-sphingolipid desaturases that catalyse different ratios of the two products 8（Z）- and 8（E）-C18-phytosphingenine. The aluminium tolerance of transgenic yeasts expressing BrD8A/B/C/D was enhanced compared with that of control cells. Expression of BrD8A in Arabidopsis changed the ratio of 8（Z）：8（E）-C 18-phytosphingenine in transgenic plants. The information reported here provides new insights into the biochemical functional diversity and evolutionary relationship of AS-sphingolipid desaturase in plants and lays a foundation for further investigation of the mechanism of 8（Z）- and 8（E）-C18- phytosphingenine biosynthesis.展开更多
The sphingolipid (SL) signaling pathways are induced by reactive oxygen species and proin-flammatory molecules, which are shown to be upregulated in the obese state. The present work was conducted to determine if an a...The sphingolipid (SL) signaling pathways are induced by reactive oxygen species and proin-flammatory molecules, which are shown to be upregulated in the obese state. The present work was conducted to determine if an altered SL pathway exists, and contributes to the pathogenesis of hepatic steatosis associated with obesity. Steatotic and non-steatotic livers were procured from Zucker Obese female rats and their lean counterparts in this pre-clinical study, and assessed for enzymes involved in degradation as well as in phos-phorylation of proapoptotic SLs. The expression of enzymes [sphingo-myelinase (SMase), ceramidase, and sphingosine kinase-1 (SK1)] and apoptotic proteins (Bax and Bcl-2) was quantified by ELISA and by Western Blot. Sphingomyelin (SM), ceramide, ceramide-1 phosphate (C1P), sphingosine (SPH), and sphingosine-1-phosphate (S1P) levels were quantified by high-performance liquid chroma-tography (HPLC)-tandem mass spectroscopy (MS). Obese steatotic livers exhibited significantly upregulated ceramidase and down-regulated SK1 and C1P levels (P < 0.05), as well as significantly lower levels of SM and higher levels of ceramide species containing long chain fatty acids, compared to their lean counterparts. These findings demonstrate that obese liver harbours SLs that favour a proapoptotic environment. Moreover, accumulation of ceramides containing long chain fatty acids could be involved in the pathogenesis of hepatic steatosis.展开更多
The sphingolipid metabolites ceramide,sphingosine,and sphingosine-1-phosphate(S1P) and its enzyme sphingosine kinase(SphK) play an important role in the regulation of cell proliferation,survival,inflammation,and cell ...The sphingolipid metabolites ceramide,sphingosine,and sphingosine-1-phosphate(S1P) and its enzyme sphingosine kinase(SphK) play an important role in the regulation of cell proliferation,survival,inflammation,and cell death.Ceramide and sphingosine usually inhibit proliferation and promote apoptosis,while its metabolite S1P phosphorylated by SphK stimulates growth and suppresses apoptosis.Because these metabolites are interconvertible,it has been proposed that it is not the absolute amounts of these metabolites but rather their relative levels that determine cell fate.The relevance of this "sphingolipid rheostat" and its role in regulating cell fate has been borne out by work in many labs using many different cell types and experimental manipulations.A central finding of these studies is that SphK is a critical regulator of the sphingolipid rheostat,as it not only produces the pro-growth,anti-apoptotic messenger S1P,but also decreases levels of pro-apoptotic ceramide and sphingosine.Activation of bioactive sphingolipid S1P signaling has emerged as a critical protective pathway in response to acute ischemic injury in both cardiac and cerebrovascular disease,and these observations have considerable relevance for future potential therapeutic targets.展开更多
Lipidomics approach by UPLC-Q-Exactive-MS was used for the identification,quantification,comparison,and characterization of sphingolipids in virus infected marine Emiliania huxleyi BOF92 cells.The results show that 16...Lipidomics approach by UPLC-Q-Exactive-MS was used for the identification,quantification,comparison,and characterization of sphingolipids in virus infected marine Emiliania huxleyi BOF92 cells.The results show that 16 significantly changed sphingolipids(including Cer,CerG1,and SPHm)were identified during viral infection.Our data confirmed previously recognized facts that viral infection led to a shift toward virus-specific sphingolipids,which is consistent with the down-regulation of genes involved in the host de novo sphingolipid biosynthesis.Moreover,we revealed the upregulation of virusencoded homologous genes participating in de novo sphingolipids biosynthesis and virus-specific hydroxylated long chain bases(LCBs)as phytoCer,suggesting the competitive inhibition of host sphingolipid synthesis to produce the required building blocks for viral production,replication,and assembly.Additionally,Cer 40꞉1;2,Cer 40꞉2;2 isomer,and CerG139꞉0;2,Cer 39꞉0;2 as novel metabolite markers might indicate the general dysfunctions in E.huxleyi in response to viral infection.Our results show that viral infection led to a profound remodeling of host sphingolipidome,by which viruses depend on the hijacking of host sphingolipid metabolism to support the viral life cycle.展开更多
The sphingosine kinases, SK1 and SK2, produce the potent signaling lipid sphingosine-1-phosphate (S1P). These enzymes have garnered increasing interest for their roles in tumorigenesis, inflammation, vascular diseases...The sphingosine kinases, SK1 and SK2, produce the potent signaling lipid sphingosine-1-phosphate (S1P). These enzymes have garnered increasing interest for their roles in tumorigenesis, inflammation, vascular diseases, and immunity, as well as other functions. The sphingosine kinases are considered signaling enzymes by producing S1P, and their activity is acutely regulated by a variety of agonists. However, these enzymes are also key players in the control of sphingolipid metabolism. A variety of sphingolipids, such as sphingosine and the ceramides, are potent signaling molecules in their own right. The role of sphingosine kinases in regulating sphingolipid metabolism is potentially a critical aspect of their signaling function. A central aspect of signaling lipids is that their hydrophobic nature constrains them to membranes. Most enzymes of sphingolipid metabolism, including the enzymes that degrade S1P, are membrane enzymes. Therefore the localization of the sphingosine kinases and S1P is likely to be important in S1P signaling. Sphingosine kinase localization affects sphingolipid signaling in several ways. Translocation of SK1 to theplasma membrane promotes extracellular secretion of S1P. SK1 and SK2 localization to specific sites appears to direct S1P to intracellular protein effectors. SK localization also determines the access of these enzymes to their substrates. This may be an important mechanism for the regulation of ceramide biosynthesis by diverting dihydrosphingosine, a precursor in the ceramide biosynthetic pathway, from the de novo production of ceramide.展开更多
Objective:Cholangiocarcinoma(CCA)is a rare but highly malignant hepatobiliary cancer with a very poor prognosis and limited treatment options.CCA is commonly associated with chronic cholestasis and significantly eleva...Objective:Cholangiocarcinoma(CCA)is a rare but highly malignant hepatobiliary cancer with a very poor prognosis and limited treatment options.CCA is commonly associated with chronic cholestasis and significantly elevated levels of primary and conjugated bile acids(CBAs),which are correlated with bile duct obstruction.展开更多
Cisplatin,a DNA crosslinking agent,is widely used for the treatment of a variety of solid tumors.Numerous studies have demonstrated that sphingolipid metabolism,which acts as a target for cisplatin treatment,is a high...Cisplatin,a DNA crosslinking agent,is widely used for the treatment of a variety of solid tumors.Numerous studies have demonstrated that sphingolipid metabolism,which acts as a target for cisplatin treatment,is a highly complex network that consists of sphingolipid signaling molecules and related catalytic enzymes.Ceramide(Cer),which is the central molecule of this network,has been established to induce apoptosis.However,another molecule,sphingosine-1-phosphate(S1P),exerts the opposite function,i.e.,serves as a regulator of pro-survival.Other sphingolipid molecules,including dihydroceramide,ceramide-1-phosphate,glucosylceramide(Glu Cer),and sphingosine(Sph),or sphingolipid catalytic enzymes such as Sph kinase(Sph K),Cer synthase(Cer S),and S1 P lyase,have also attracted considerable attention,particularly Cer,Glu Cer,Sph K,Cer S,and S1 P lyase,which have been implicated in cisplatin resistance.This review summarizes specific molecules involved in sphingolipid metabolism and related catalytic enzymes affecting the anticancer effect of cisplatin,particularly in relation to induction of apoptosis and drug resistance.展开更多
Background:Renal osteodystrophy(ROD)is a skeletal pathology associated with chronic kidney disease-mineral and bone disorder(CKD-MBD)that is characterized by aberrant bone mineralization and remodeling.ROD increases t...Background:Renal osteodystrophy(ROD)is a skeletal pathology associated with chronic kidney disease-mineral and bone disorder(CKD-MBD)that is characterized by aberrant bone mineralization and remodeling.ROD increases the risk of fracture and mortality in CKD patients.The underlying mechanisms of ROD remain elusive,partially due to the absence of an appropriate animal model.To address this gap,we established a stable mouse model of ROD using an optimized adenine-enriched diet and conducted exploratory analyses through ribonucleic acid sequencing(RNA-seq).Methods:Eight-week-old male C57BL/6J mice were randomly allocated into three groups:control group(n=5),adenine and high-phosphate(HP)diet group(n=20),and the optimized adenine-containing diet group(n=20)for 12 weeks.We assessed the skeletal characteristics of model mice through blood biochemistry,microcomputed tomography(micro-CT),and bone histomorphometry.RNA-seq was utilized to profile gene expression changes of ROD.We elucidated the functions of differentially expressed genes(DEGs)using gene ontology(GO)analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,and gene set enrichment analysis(GSEA).DEGs were validated via quantitative real-time polymerase chain reaction(qRT-PCR).Results:By the fifth week,adenine followed by an HP diet induced rapid weight loss and high mortality rates in the mouse group,precluding further model development.Mice with optimized adenine diet-induced ROD displayed significant abnormalities in serum creatinine and blood urea nitrogen levels,accompanied by pronounced hyperparathyroidism and hyperphosphatemia.The femur bone mineral density(BMD)of the model mice was lower than that of control mice,with substantial bone loss and cortical porosity.ROD mice exhibited substantial bone turnover with an increase in osteoblast and osteoclast markers.Transcriptomic profiling revealed 1907 genes with upregulated expression and 723 genes with downregulated expression in the femurs of ROD mice relative to those of control mice.Pathway analyses indicated significant enrichment of upregulated genes in the sphingolipid metabolism pathway.The significant upregulation of alkaline ceramidase 1(Acer1),alkaline ceramidase 2(Acer2),prosaposin-like 1(Psapl1),adenosine A1 receptor(Adora1),and sphingosine-1-phosphate receptor 5(S1pr5)were successfully validated in mouse femurs by qRT-PCR.Conclusions:Optimized adenine diet mouse model may be a valuable proxy for studying ROD.RNA-seq analysis revealed that the sphingolipid metabolism pathway is likely a key player in ROD pathogenesis,thereby providing new avenues for therapeutic intervention.展开更多
Callose,aβ-1,3-glucan plant cell wall polymer,regulates symplasmic channel size at plasmodesmata(PD)and plays a crucial role in a variety of plant processes.However,elucidating the molecular mechanism of PD callose h...Callose,aβ-1,3-glucan plant cell wall polymer,regulates symplasmic channel size at plasmodesmata(PD)and plays a crucial role in a variety of plant processes.However,elucidating the molecular mechanism of PD callose homeostasis is limited.We screened and identified an Arabidopsis mutant plant with excessive callose deposition at PD and found that the mutated gene wasα1-COP,a member of the coat protein I(COPI)coatomer complex.We report that loss of function ofα1-COP elevates the callose accumulation at PD by affecting subcellular protein localization of callose degradation enzyme Pd BG2.This process is linked to the functions of ERH1,an inositol phosphoryl ceramide synthase,and glucosylceramide synthase through physical interactions with theα1-COP protein.Additionally,the loss of function ofα1-COP alters the subcellular localization of ERH1 and GCS proteins,resulting in a reduction of Glc Cers and Glc HCers molecules,which are key sphingolipid(SL)species for lipid raft formation.Our findings suggest thatα1-COP protein,together with SL modifiers controlling lipid raft compositions,regulates the subcellular localization of GPI-anchored PDBG2 proteins,and hence the callose turnover at PD and symplasmic movement of biomolecules.Our findings provide the first key clue to link the COPI-mediated intracellular trafficking pathway to the callose-mediated intercellular signaling pathway through PD.展开更多
Although the cell membrane and cytoskeleton play essential roles in cellular morphogenesis,the interaction between the membrane and cytoskeleton is poorly understood.Cotton fibers are extremely elongated single cells,...Although the cell membrane and cytoskeleton play essential roles in cellular morphogenesis,the interaction between the membrane and cytoskeleton is poorly understood.Cotton fibers are extremely elongated single cells,which makes them an ideal model for studying cell development.Here,we used the sphingolipid biosynthesis inhibitor,fumonisin B1(FB1),and found that it effectively suppressed the myeloblastosis(MYB)transcription factor GhMYB86,thereby negatively affecting fiber elongation.A direct target of GhMYB86 is GhTUB7,which encodes the tubulin protein,the major component of the microtubule cytoskeleton.Interestingly,both the overexpression of GhMYB86 and GhTUB7 caused an ectopic microtubule arrangement at the fiber tips,and then leading to shortened fibers.Moreover,we found that GhMBE2 interacted with GhMYB86 and that FB1 and reactive oxygen species induced its transport into the nucleus,thereby enhancing the promotion of GhTUB7 by GhMYB86.Overall,we established a GhMBE2-GhMYB86-GhTUB7 regulation module for fiber elongation and revealed that membrane sphingolipids affect fiber elongation by altering microtubule arrangement.展开更多
Plant sphingolipids are not only structural components of the plasma membrane and other endomembrane systems but also act as signaling molecules during biotic and abiotic stresses.However,the roles of sphingolipids in...Plant sphingolipids are not only structural components of the plasma membrane and other endomembrane systems but also act as signaling molecules during biotic and abiotic stresses.However,the roles of sphingolipids in plant signal transduction in response to environmental cues are yet to be investigated in detail. In this review,we discuss the signaling roles of sphingolipid metabolites with a focus on plant sphingolipids.We also mention some microbial sphingolipids that initiate signals during their interaction with plants, because of the limited literatures on their plant analogs.The equilibrium of nonphosphorylated and phosphorylated sphingolipid species determine the destiny of plant cells,whereas molecular connections among the enzymes responsible for this equilibrium in a coordinated signaling network are poorly understood.A mechanistic link between the phytohormone-sphingolipid interplay has also not yet been fully understood and many key participants involved in this complex interaction operating under stress conditions await to be identified.Future research is needed to fill these gaps and to better understand the signal pathways of plant sphingolipids and their interplay with other signals in response to environmental stresses.展开更多
Synapses are key structures involved in transmitting information in the nervous system,and their functions rely on the regulation of various lipids.Lipids play important roles in synapse formation,neurotransmitter rel...Synapses are key structures involved in transmitting information in the nervous system,and their functions rely on the regulation of various lipids.Lipids play important roles in synapse formation,neurotransmitter release,and signal transmission,and dysregulation of lipid metabolism is closely associated with various neurodegenerative diseases.The complex roles of lipids in synaptic function and neurological diseases have recently garnered increasing attention,but their specific mechanisms remain to be fully understood.This review aims to explore how lipids regulate synaptic activity in the central nervous system,focusing on their roles in synapse formation,neurotransmitter release,and signal transmission.Additionally,it discusses the mechanisms by which glial cells modulate synaptic function through lipid regulation.This review shows that within the central nervous system,lipids are essential components of the cell membrane bilayer,playing critical roles in synaptic structure and function.They regulate presynaptic vesicular trafficking,postsynaptic signaling pathways,and glial-neuronal interactions.Cholesterol maintains membrane fluidity and promotes the formation of lipid rafts.Glycerophospholipids contribute to the structural integrity of synaptic membranes and are involved in the release of synaptic vesicles.Sphingolipids interact with synaptic receptors through various mechanisms to regulate their activity and are also involved in cellular processes such as inflammation and apoptosis.Fatty acids are vital for energy metabolism and the synthesis of signaling molecules.Abnormalities in lipid metabolism may lead to impairments in synaptic function,affecting information transmission between neurons and the overall health of the nervous system.Therapeutic strategies targeting lipid metabolism,particularly through cholesterol modulation,show promise for treating these conditions.In neurodegenerative diseases such as Alzheimer’s disease,Parkinson disease,and amyotrophic lateral sclerosis,dysregulation of lipid metabolism is closely linked to synaptic dysfunction.Therefore,lipids are not only key molecules in neural regeneration and synaptic repair but may also contribute to neurodegenerative pathology when metabolic dysregulation occurs.Further research is needed to elucidate the specific mechanisms linking lipid metabolism to synaptic dysfunction and to develop targeted lipid therapies for neurological diseases.展开更多
Sphingolipids are not only a pivotal component of membranes but also act as bioactive molecules.Cotton fiber is one of the longest plant cells and sphingolipids are closely associated with the development of cotton fi...Sphingolipids are not only a pivotal component of membranes but also act as bioactive molecules.Cotton fiber is one of the longest plant cells and sphingolipids are closely associated with the development of cotton fiber cells.However,their function in cotton fiber cell development and its action mechanism is unclear.Through cotton genetic transformation and chemistry biological approach,we identified the function and action mechanism of the glucosylceramide synthase gene GhGCS1 and its product glucosylceramide(GluCer)in cotton fiber growth.GhGCS1 was preferentially expressed at the stage of fiber elongation and localized in the endoplasmic reticulum.Overexpression of GhGCS1 promoted GluCer synthesis and fiber elongation,which was consistent with the exogenous application of GluCer(FA-C22)(containing very long-acyl-chain fatty acid)to cotton fiber in ovule culture system in vitro.Contrarily,suppressing GhGCS1 expression inhibited GluCer synthesis and fiber elongation,which was similar as the exogenous application of GluCer synthesis inhibitor,PDMP.Transcriptome analysis revealed that the fiber elongation regulated by GhGCS1 was associated with brassinosteroid(BR)synthesis and signaling related gene expression.Meanwhile,we detected the BL content of control and transgenic fiber cells.The BL content significantly increased and decreased in up-and down-regulated transgenic fibers when compared with control fibers,respectively.Furthermore,we found that PDMP treatment blocked BR synthesis and signal transduction,while exogenous application of GluCer could enhance BR synthesis and signaling.Overall,our results revealed that GhGCS1 and GluCer regulated cotton fiber elongation by influencing BR synthesis and signaling.Our study shed a novel insight on regulatory mechanism of cotton fiber elongation and provides theoretical support,genetic resources and novel transgenic materials for improvement of crop quality.展开更多
The Elongator complex is conserved in a wide range of species and plays crucial roles in diverse cellular processes.We have previously shown that the Elongator protein PoElp3 was involved in the asexual development,pa...The Elongator complex is conserved in a wide range of species and plays crucial roles in diverse cellular processes.We have previously shown that the Elongator protein PoElp3 was involved in the asexual development,pathogenicity,and autophagy of the rice blast fungus.In this study,we further revealed that PoElp3 functions via tRNA-mediated protein integrity.Phenotypic analyses revealed that overexpression of two of the tRNAs,tK(UUU)and tQ(UUG)could rescue the defects inΔPoelp3 strain.TMT-based proteomic and transcriptional analyses demonstrated that 386 proteins were down-regulated inΔPoelp3 strain compared with wild type strain Guy11,in a transcription-independent manner.Codon usage assays revealed an enrichment of Glutamine CAA-biased mRNA in the 386 proteins compared with the 70-15 genome.In addition to those reported previously,we also found that PoErp9,a sphingolipid C9-methyltransferase,was down-regulated in theΔPoelp3strain.Through an ILV2-specific integration of PoERP9-GFP into the wild type andΔPoelp3 strain,we were able to show that PoErp9 was positively regulated by PoElp3 translationally but not transcriptionally.Functional analyses revealed that PoErp9 was involved in the fungal growth,conidial development,pathogenicity,and TORrelated autophagy homeostasis in Pyricularia oryzae.Taken together,our results suggested that PoElp3 acts through the tRNA-mediated translational efficiency to regulate asexual development,pathogenicity,sphingolipid metabolism,and autophagy in the rice blast fungus.展开更多
基金supported by the Judith Jane Mason and Harold Stannett Williams Memorial Foundation National Medical Program(#Mason2210)to JX。
文摘Myalgic encephalomyelitis/chronic fatigue syndrome-an insidious disease:The recent COVID-19 pandemic has brought substantial attention to the overlapping symptoms between long COVID and myalgic encephalomyelitis/chronic fatigue syndrome(ME/CFS),a chronic and poorly understood neurological disorder(Shankar et al.,2024).
基金supported by grants from National Key R&D Program of China(2018YFA0506900,2018YFA0800901)the National Natural Science Foundation of China(NSFC92057202)the Chinese Academy of Sciences(XDB39050900).
文摘Sphingolipids not only exert structural roles in cellular membranes,but also act as signaling molecules in various physiological and pathological processes.A myriad of studies have shown that abnormal levels of sphingolipids and their metabolic enzymes are associated with a variety of human diseases.Moreover,blood sphingolipids can also be used as biomarkers for disease diagnosis.This review summarizes the biosynthesis,metabolism,and pathological roles of sphingolipids,with emphasis on the biosynthesis of ceramide,the precursor for the biosynthesis of complex sphingolipids with different fatty acyl chains.The possibility of using sphingolipids for disease prediction,diagnosis,and treatment is also discussed.Targeting endogenous ceramides and complex sphingolipids along with their specific fatty acyl chain to promote future drug development will also be discussed.
基金The work was supported by funds from The Science and Technology Project of Hangzhou City(Agriculture and Social Development,No.2016007)&(Agriculture and Social Development,No.20201231Y131)&(Social Development,No.20140633B57)The Science and Technology Project of Yuhang District,Hangzhou City(Nos.2017002&2014003)+2 种基金The Health Science and Technology Project of Hangzhou City(No.2015B32)Zhejiang Provincial Natural Science Foundation of China under Grant(No.LTGY23H160006)The Health Science and Technology Project of Zhejiang Province(No.2023XY009).
文摘Background:The specific impact of sphingolipid metabolism on developing hepatocellular Carcinoma(HCC)remains unclear.This study aims to explore the relationship between sphingolipid metabolism and HCC prognosis,immune response,and drug sensitivity.Methods:Data were obtained from The Cancer Genome Atlas(TCGA)-Hepatocellular Carcinoma(LIHC)and Gene Expression Omnibus(GEO,GSE14520 datasets).47 sphingolipid metabolism genes were obtained from the Kyoto Encyclopedia of Genes and Genomes(KEGG)database.After classifying HCC samples using the Non-negative Matrix Factorization(NMF)clustering method,differentially expressed genes were screened.Then,8 risk genes were obtained by univariate analysis,survival random forest reduction and lasso analysis.The expression of 8 risk genes was verified in vitro.Results:8 risk genes were used to construct the Sphingolipid score model.High-Sphingolipid score predicted poor prognosis of HCC patients.Sphingolipid score was associated with immune checkpoints(IL-1B,TLR4,TGFB1,and IL-10),immune cells(Th2,Treg,MDSC,Neutrophil,Fibroblasts and macrophage),and MAPK Cascade.In the High-Sphingolipid score group,a significantly higher proportion of patients with TP53(p53)mutations was significantly higher(56%).Furthermore,patients with a high-Sphingolipid score were predicted to have a higher sensitivity to chemotherapy drugs.In vitro validation showed that compared with normal liver cells LX-2,TRIM47,and S100A9 significantly increased in liver cancer cells Hep G2,MHCC-97H,and Hep3B2.1-7,while SLC1A7,LPCAT1,and CFHR4 significantly decreased.Silencing TRIM47 reduced the proliferation and promoted apoptosis.The levels of ceramide synthesis-related indexes(CERS1,CERS6,CERS5,and SPTLC2)increased,and the ACER3 related to catalytic hydrolysis decreased.Conclusion:We constructed a sphingolipid metabolism-related prognostic signature(Sphingolipid score)based on 8 risk genes.TRIM47 may affect the development of liver cancer by regulating the relevant indicators of ceramide synthesis and catalytic hydrolysis.
基金the National ＂863＂ Program of China （No. 2001AA624010）the Guangdong Provincial Natural Science Foundation of China （No. 04300674）+1 种基金 the Guangdong Provincial Science and Technology Program Foundation of China （No.2004B30101017） the Foshan City Foundation for the Development of Science and Technology （No. 2005081871）.
文摘A set of three sphingolipids, N-2′-hydroxyplmitoyl-1-O-β-D-glucopyranosyl-9-methyl-4E, 8E-sphingadiene （A）, N-2′-hydroxyl-3′E-octadecenoyl-1-O-β-D-glucopyranosyl-9-methyl-4E, 8E-sphingediene （B） and N-palmitoyldihydrosphingosine （C）, were isolated from two marine-derived mangrove endophytic fungal strains （strains No. 1924 and 3893） from the South China Sea. Their structures were elucidated by 2D NMR and FABMS methods. It is the first time that these sphingolipids were separated and obtained from marine-derived mangrove endophytic fungus from the South China Sea.
基金supported by the National High-tech R&D Program(863 Program,No.2006AA10A113) of the Ministry of Science and Technology of Chinathe projects of Ministry of Agriculture of China for Transgenic Research (Nos.2009ZX08009-098B and 2008ZX08009-003)
文摘8-Sphingolipid desaturase is the key enzyme that catalyses desaturation at the C8 position of the long-chain base of sphingolipids in higher plants. There have been no previous studies on the genes encoding AS-sphingolipid desaturases in Brassica rapa. In this study, four genes encoding AS-sphingolipid desaturases from B. rapa were isolated and characterised. Phylogenetic analyses indicated that these genes could be divided into two groups： BrD8A, BrD8C and BrD8D in group I, and BrD8B in group II. The two groups of genes diverged before the separation of Arabidopsis and Brassica. Though the four genes shared a high sequence similarity, and their coding desaturases all located in endoplasmic reticulum, they exhibited distinct expression patterns. Heterologous expression in Saccharomyces cerevisiae revealed that BrD8A/B/C/D were functionally diverse AS-sphingolipid desaturases that catalyse different ratios of the two products 8（Z）- and 8（E）-C18-phytosphingenine. The aluminium tolerance of transgenic yeasts expressing BrD8A/B/C/D was enhanced compared with that of control cells. Expression of BrD8A in Arabidopsis changed the ratio of 8（Z）：8（E）-C 18-phytosphingenine in transgenic plants. The information reported here provides new insights into the biochemical functional diversity and evolutionary relationship of AS-sphingolipid desaturase in plants and lays a foundation for further investigation of the mechanism of 8（Z）- and 8（E）-C18- phytosphingenine biosynthesis.
文摘The sphingolipid (SL) signaling pathways are induced by reactive oxygen species and proin-flammatory molecules, which are shown to be upregulated in the obese state. The present work was conducted to determine if an altered SL pathway exists, and contributes to the pathogenesis of hepatic steatosis associated with obesity. Steatotic and non-steatotic livers were procured from Zucker Obese female rats and their lean counterparts in this pre-clinical study, and assessed for enzymes involved in degradation as well as in phos-phorylation of proapoptotic SLs. The expression of enzymes [sphingo-myelinase (SMase), ceramidase, and sphingosine kinase-1 (SK1)] and apoptotic proteins (Bax and Bcl-2) was quantified by ELISA and by Western Blot. Sphingomyelin (SM), ceramide, ceramide-1 phosphate (C1P), sphingosine (SPH), and sphingosine-1-phosphate (S1P) levels were quantified by high-performance liquid chroma-tography (HPLC)-tandem mass spectroscopy (MS). Obese steatotic livers exhibited significantly upregulated ceramidase and down-regulated SK1 and C1P levels (P < 0.05), as well as significantly lower levels of SM and higher levels of ceramide species containing long chain fatty acids, compared to their lean counterparts. These findings demonstrate that obese liver harbours SLs that favour a proapoptotic environment. Moreover, accumulation of ceramides containing long chain fatty acids could be involved in the pathogenesis of hepatic steatosis.
基金Supported by Grants from the National Institutes of Health (NS40516,to Yenari MA)the Veteran's Merit Award(Yenari MA)+3 种基金the Uehara Foundation(2013 Research Fellowship,to Kawabori M)the National Heart,Lung,and Blood Institute/NHLBI(1P01 HL 68738 and R01 HL 090606 to Karliner JS)Grants to Yenari MA and Karliner JS were administered by the Northern California Institute for Research and Educationsupported by resources of the Veterans Affairs Medical Center, San Francisco,California
文摘The sphingolipid metabolites ceramide,sphingosine,and sphingosine-1-phosphate(S1P) and its enzyme sphingosine kinase(SphK) play an important role in the regulation of cell proliferation,survival,inflammation,and cell death.Ceramide and sphingosine usually inhibit proliferation and promote apoptosis,while its metabolite S1P phosphorylated by SphK stimulates growth and suppresses apoptosis.Because these metabolites are interconvertible,it has been proposed that it is not the absolute amounts of these metabolites but rather their relative levels that determine cell fate.The relevance of this "sphingolipid rheostat" and its role in regulating cell fate has been borne out by work in many labs using many different cell types and experimental manipulations.A central finding of these studies is that SphK is a critical regulator of the sphingolipid rheostat,as it not only produces the pro-growth,anti-apoptotic messenger S1P,but also decreases levels of pro-apoptotic ceramide and sphingosine.Activation of bioactive sphingolipid S1P signaling has emerged as a critical protective pathway in response to acute ischemic injury in both cardiac and cerebrovascular disease,and these observations have considerable relevance for future potential therapeutic targets.
基金Supported by the National Natural Science Foundation of China(Nos.42076086,41576166)the Natural Science Foundation of Fujian Province(No.2020J05138)+1 种基金the Education and Research Project for Young and Middle-aged Teachers of Fujian Province(No.JAT190343)the Cultivation Plan for Distinguished Young Scholars in Fujian Universities。
文摘Lipidomics approach by UPLC-Q-Exactive-MS was used for the identification,quantification,comparison,and characterization of sphingolipids in virus infected marine Emiliania huxleyi BOF92 cells.The results show that 16 significantly changed sphingolipids(including Cer,CerG1,and SPHm)were identified during viral infection.Our data confirmed previously recognized facts that viral infection led to a shift toward virus-specific sphingolipids,which is consistent with the down-regulation of genes involved in the host de novo sphingolipid biosynthesis.Moreover,we revealed the upregulation of virusencoded homologous genes participating in de novo sphingolipids biosynthesis and virus-specific hydroxylated long chain bases(LCBs)as phytoCer,suggesting the competitive inhibition of host sphingolipid synthesis to produce the required building blocks for viral production,replication,and assembly.Additionally,Cer 40꞉1;2,Cer 40꞉2;2 isomer,and CerG139꞉0;2,Cer 39꞉0;2 as novel metabolite markers might indicate the general dysfunctions in E.huxleyi in response to viral infection.Our results show that viral infection led to a profound remodeling of host sphingolipidome,by which viruses depend on the hijacking of host sphingolipid metabolism to support the viral life cycle.
基金Supported by The James Graham Brown Cancer Center and NIH, No. CA111987
文摘The sphingosine kinases, SK1 and SK2, produce the potent signaling lipid sphingosine-1-phosphate (S1P). These enzymes have garnered increasing interest for their roles in tumorigenesis, inflammation, vascular diseases, and immunity, as well as other functions. The sphingosine kinases are considered signaling enzymes by producing S1P, and their activity is acutely regulated by a variety of agonists. However, these enzymes are also key players in the control of sphingolipid metabolism. A variety of sphingolipids, such as sphingosine and the ceramides, are potent signaling molecules in their own right. The role of sphingosine kinases in regulating sphingolipid metabolism is potentially a critical aspect of their signaling function. A central aspect of signaling lipids is that their hydrophobic nature constrains them to membranes. Most enzymes of sphingolipid metabolism, including the enzymes that degrade S1P, are membrane enzymes. Therefore the localization of the sphingosine kinases and S1P is likely to be important in S1P signaling. Sphingosine kinase localization affects sphingolipid signaling in several ways. Translocation of SK1 to theplasma membrane promotes extracellular secretion of S1P. SK1 and SK2 localization to specific sites appears to direct S1P to intracellular protein effectors. SK localization also determines the access of these enzymes to their substrates. This may be an important mechanism for the regulation of ceramide biosynthesis by diverting dihydrosphingosine, a precursor in the ceramide biosynthetic pathway, from the de novo production of ceramide.
文摘Objective:Cholangiocarcinoma(CCA)is a rare but highly malignant hepatobiliary cancer with a very poor prognosis and limited treatment options.CCA is commonly associated with chronic cholestasis and significantly elevated levels of primary and conjugated bile acids(CBAs),which are correlated with bile duct obstruction.
文摘Cisplatin,a DNA crosslinking agent,is widely used for the treatment of a variety of solid tumors.Numerous studies have demonstrated that sphingolipid metabolism,which acts as a target for cisplatin treatment,is a highly complex network that consists of sphingolipid signaling molecules and related catalytic enzymes.Ceramide(Cer),which is the central molecule of this network,has been established to induce apoptosis.However,another molecule,sphingosine-1-phosphate(S1P),exerts the opposite function,i.e.,serves as a regulator of pro-survival.Other sphingolipid molecules,including dihydroceramide,ceramide-1-phosphate,glucosylceramide(Glu Cer),and sphingosine(Sph),or sphingolipid catalytic enzymes such as Sph kinase(Sph K),Cer synthase(Cer S),and S1 P lyase,have also attracted considerable attention,particularly Cer,Glu Cer,Sph K,Cer S,and S1 P lyase,which have been implicated in cisplatin resistance.This review summarizes specific molecules involved in sphingolipid metabolism and related catalytic enzymes affecting the anticancer effect of cisplatin,particularly in relation to induction of apoptosis and drug resistance.
基金funded by the National Natural Science Foundation of China(No.82370742)the Key Program of Jiangsu Health and Health Committee(No.ZD2022045).
文摘Background:Renal osteodystrophy(ROD)is a skeletal pathology associated with chronic kidney disease-mineral and bone disorder(CKD-MBD)that is characterized by aberrant bone mineralization and remodeling.ROD increases the risk of fracture and mortality in CKD patients.The underlying mechanisms of ROD remain elusive,partially due to the absence of an appropriate animal model.To address this gap,we established a stable mouse model of ROD using an optimized adenine-enriched diet and conducted exploratory analyses through ribonucleic acid sequencing(RNA-seq).Methods:Eight-week-old male C57BL/6J mice were randomly allocated into three groups:control group(n=5),adenine and high-phosphate(HP)diet group(n=20),and the optimized adenine-containing diet group(n=20)for 12 weeks.We assessed the skeletal characteristics of model mice through blood biochemistry,microcomputed tomography(micro-CT),and bone histomorphometry.RNA-seq was utilized to profile gene expression changes of ROD.We elucidated the functions of differentially expressed genes(DEGs)using gene ontology(GO)analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,and gene set enrichment analysis(GSEA).DEGs were validated via quantitative real-time polymerase chain reaction(qRT-PCR).Results:By the fifth week,adenine followed by an HP diet induced rapid weight loss and high mortality rates in the mouse group,precluding further model development.Mice with optimized adenine diet-induced ROD displayed significant abnormalities in serum creatinine and blood urea nitrogen levels,accompanied by pronounced hyperparathyroidism and hyperphosphatemia.The femur bone mineral density(BMD)of the model mice was lower than that of control mice,with substantial bone loss and cortical porosity.ROD mice exhibited substantial bone turnover with an increase in osteoblast and osteoclast markers.Transcriptomic profiling revealed 1907 genes with upregulated expression and 723 genes with downregulated expression in the femurs of ROD mice relative to those of control mice.Pathway analyses indicated significant enrichment of upregulated genes in the sphingolipid metabolism pathway.The significant upregulation of alkaline ceramidase 1(Acer1),alkaline ceramidase 2(Acer2),prosaposin-like 1(Psapl1),adenosine A1 receptor(Adora1),and sphingosine-1-phosphate receptor 5(S1pr5)were successfully validated in mouse femurs by qRT-PCR.Conclusions:Optimized adenine diet mouse model may be a valuable proxy for studying ROD.RNA-seq analysis revealed that the sphingolipid metabolism pathway is likely a key player in ROD pathogenesis,thereby providing new avenues for therapeutic intervention.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korea Government(MSIT)(Grant Nos.NRF 2018R1A2A1A05077295,2020M3A9I4038352,2022R1A2C3010331,2020R1A6A1A03044344,and 2022R1A 5A1031361)a grant from the New Breeding Technologies Development Program(Grant No.PJ01653202),Rural Development Administration(RDA),Republic of Korea。
文摘Callose,aβ-1,3-glucan plant cell wall polymer,regulates symplasmic channel size at plasmodesmata(PD)and plays a crucial role in a variety of plant processes.However,elucidating the molecular mechanism of PD callose homeostasis is limited.We screened and identified an Arabidopsis mutant plant with excessive callose deposition at PD and found that the mutated gene wasα1-COP,a member of the coat protein I(COPI)coatomer complex.We report that loss of function ofα1-COP elevates the callose accumulation at PD by affecting subcellular protein localization of callose degradation enzyme Pd BG2.This process is linked to the functions of ERH1,an inositol phosphoryl ceramide synthase,and glucosylceramide synthase through physical interactions with theα1-COP protein.Additionally,the loss of function ofα1-COP alters the subcellular localization of ERH1 and GCS proteins,resulting in a reduction of Glc Cers and Glc HCers molecules,which are key sphingolipid(SL)species for lipid raft formation.Our findings suggest thatα1-COP protein,together with SL modifiers controlling lipid raft compositions,regulates the subcellular localization of GPI-anchored PDBG2 proteins,and hence the callose turnover at PD and symplasmic movement of biomolecules.Our findings provide the first key clue to link the COPI-mediated intracellular trafficking pathway to the callose-mediated intercellular signaling pathway through PD.
基金funded by the National Natural Science Foundation of China(31571722 and 31971984)the Genetically Modified Organisms Breeding Major Project of China(No.2018ZX0800921B)Fundamental Research Funds for the Central Universities(SWU‐XDJH202315).
文摘Although the cell membrane and cytoskeleton play essential roles in cellular morphogenesis,the interaction between the membrane and cytoskeleton is poorly understood.Cotton fibers are extremely elongated single cells,which makes them an ideal model for studying cell development.Here,we used the sphingolipid biosynthesis inhibitor,fumonisin B1(FB1),and found that it effectively suppressed the myeloblastosis(MYB)transcription factor GhMYB86,thereby negatively affecting fiber elongation.A direct target of GhMYB86 is GhTUB7,which encodes the tubulin protein,the major component of the microtubule cytoskeleton.Interestingly,both the overexpression of GhMYB86 and GhTUB7 caused an ectopic microtubule arrangement at the fiber tips,and then leading to shortened fibers.Moreover,we found that GhMBE2 interacted with GhMYB86 and that FB1 and reactive oxygen species induced its transport into the nucleus,thereby enhancing the promotion of GhTUB7 by GhMYB86.Overall,we established a GhMBE2-GhMYB86-GhTUB7 regulation module for fiber elongation and revealed that membrane sphingolipids affect fiber elongation by altering microtubule arrangement.
基金the National Natural Science Foundation of China (31570808)the Fundamental Research Funds for the Central Universities (2662015PY090).
文摘Plant sphingolipids are not only structural components of the plasma membrane and other endomembrane systems but also act as signaling molecules during biotic and abiotic stresses.However,the roles of sphingolipids in plant signal transduction in response to environmental cues are yet to be investigated in detail. In this review,we discuss the signaling roles of sphingolipid metabolites with a focus on plant sphingolipids.We also mention some microbial sphingolipids that initiate signals during their interaction with plants, because of the limited literatures on their plant analogs.The equilibrium of nonphosphorylated and phosphorylated sphingolipid species determine the destiny of plant cells,whereas molecular connections among the enzymes responsible for this equilibrium in a coordinated signaling network are poorly understood.A mechanistic link between the phytohormone-sphingolipid interplay has also not yet been fully understood and many key participants involved in this complex interaction operating under stress conditions await to be identified.Future research is needed to fill these gaps and to better understand the signal pathways of plant sphingolipids and their interplay with other signals in response to environmental stresses.
文摘目的探讨玄参总苷的主要化学成分及其干预大鼠甲亢阴虚火旺证模型的作用机制。方法将SD大鼠随机分为对照组、模型组、玄参总苷给药组。腹腔注射3′,5-三碘代-L-甲状腺原氨酸(3,5,3'-triiodothyronine,T3)溶液[100μg·(100 g)^(-1)]建立阴虚火旺模型,进行环磷酸腺苷(cyclic adenosine monophosphate,cAMP)、环磷酸鸟苷(cyclic guanosine monophosphate,cGMP)水平等相关指标的检测,采用超高效液相色谱-四极杆-飞行时间串联质谱技术(ultra high performance liquid chromatography-quadrupole-time of flight mass spectrometry,UHPLC-Q-TOF-MS)对玄参总苷的化学成分和不同组别大鼠的血清内源性代谢物进行分析,并结合主成分分析(principal component analysis,PCA)和正交偏最小二乘判别分析(orthogonal partial least squares-discriminant analysis,OPLS-DA),筛选差异性代谢物并构建其代谢通路。结果从玄参总苷中共鉴定了31个化学成分,玄参总苷能显著降低阴虚大鼠cAMP、cAMP/cGMP水平,阴虚火旺模型大鼠血清中25个内源性代谢物发生显著变化,其中鞘脂、类固醇、脂质、亚油酸、花生四烯酸呈上升趋势,通路分析表明玄参总苷可能通过调节鞘脂类、甘油磷脂、花生四烯酸等代谢途径改善阴虚火旺证候。结论本研究运用血清代谢组学方法揭示了玄参总苷干预甲亢阴虚火旺证的作用机制,为玄参“滋阴降火”功效的物质基础和临床应用提供了理论依据。
基金supported by the National Natural Science Foundation of China,No.82201568(to QQ)Capital’s Funds for Health Improvement and Research,No.2024-2-1031(to QQ)Beijing Nova Program,No.20240484566(to QQ).
文摘Synapses are key structures involved in transmitting information in the nervous system,and their functions rely on the regulation of various lipids.Lipids play important roles in synapse formation,neurotransmitter release,and signal transmission,and dysregulation of lipid metabolism is closely associated with various neurodegenerative diseases.The complex roles of lipids in synaptic function and neurological diseases have recently garnered increasing attention,but their specific mechanisms remain to be fully understood.This review aims to explore how lipids regulate synaptic activity in the central nervous system,focusing on their roles in synapse formation,neurotransmitter release,and signal transmission.Additionally,it discusses the mechanisms by which glial cells modulate synaptic function through lipid regulation.This review shows that within the central nervous system,lipids are essential components of the cell membrane bilayer,playing critical roles in synaptic structure and function.They regulate presynaptic vesicular trafficking,postsynaptic signaling pathways,and glial-neuronal interactions.Cholesterol maintains membrane fluidity and promotes the formation of lipid rafts.Glycerophospholipids contribute to the structural integrity of synaptic membranes and are involved in the release of synaptic vesicles.Sphingolipids interact with synaptic receptors through various mechanisms to regulate their activity and are also involved in cellular processes such as inflammation and apoptosis.Fatty acids are vital for energy metabolism and the synthesis of signaling molecules.Abnormalities in lipid metabolism may lead to impairments in synaptic function,affecting information transmission between neurons and the overall health of the nervous system.Therapeutic strategies targeting lipid metabolism,particularly through cholesterol modulation,show promise for treating these conditions.In neurodegenerative diseases such as Alzheimer’s disease,Parkinson disease,and amyotrophic lateral sclerosis,dysregulation of lipid metabolism is closely linked to synaptic dysfunction.Therefore,lipids are not only key molecules in neural regeneration and synaptic repair but may also contribute to neurodegenerative pathology when metabolic dysregulation occurs.Further research is needed to elucidate the specific mechanisms linking lipid metabolism to synaptic dysfunction and to develop targeted lipid therapies for neurological diseases.
基金funded by the National Natural Science Foundation of China(32372114,31971984)the Special Fund for Youth Team of the Southwest Universities(SWU-XJPY202306)+1 种基金the Chongqing Graduate Scientific Research Innovation Project(CYS23239)the Genetically Modified Organisms Breeding Major Project of China(2018ZX0800921B)。
文摘Sphingolipids are not only a pivotal component of membranes but also act as bioactive molecules.Cotton fiber is one of the longest plant cells and sphingolipids are closely associated with the development of cotton fiber cells.However,their function in cotton fiber cell development and its action mechanism is unclear.Through cotton genetic transformation and chemistry biological approach,we identified the function and action mechanism of the glucosylceramide synthase gene GhGCS1 and its product glucosylceramide(GluCer)in cotton fiber growth.GhGCS1 was preferentially expressed at the stage of fiber elongation and localized in the endoplasmic reticulum.Overexpression of GhGCS1 promoted GluCer synthesis and fiber elongation,which was consistent with the exogenous application of GluCer(FA-C22)(containing very long-acyl-chain fatty acid)to cotton fiber in ovule culture system in vitro.Contrarily,suppressing GhGCS1 expression inhibited GluCer synthesis and fiber elongation,which was similar as the exogenous application of GluCer synthesis inhibitor,PDMP.Transcriptome analysis revealed that the fiber elongation regulated by GhGCS1 was associated with brassinosteroid(BR)synthesis and signaling related gene expression.Meanwhile,we detected the BL content of control and transgenic fiber cells.The BL content significantly increased and decreased in up-and down-regulated transgenic fibers when compared with control fibers,respectively.Furthermore,we found that PDMP treatment blocked BR synthesis and signal transduction,while exogenous application of GluCer could enhance BR synthesis and signaling.Overall,our results revealed that GhGCS1 and GluCer regulated cotton fiber elongation by influencing BR synthesis and signaling.Our study shed a novel insight on regulatory mechanism of cotton fiber elongation and provides theoretical support,genetic resources and novel transgenic materials for improvement of crop quality.
基金supported by National Natural Science Foundation of China(32172365 and 32272513)the Central Guidance on Local Science and Technology Development Fund of Fujian Province,China(2022L3088)the Innovative Research Funding of Fujian Agriculture and Forestry University,China(CXZX2020153D)。
文摘The Elongator complex is conserved in a wide range of species and plays crucial roles in diverse cellular processes.We have previously shown that the Elongator protein PoElp3 was involved in the asexual development,pathogenicity,and autophagy of the rice blast fungus.In this study,we further revealed that PoElp3 functions via tRNA-mediated protein integrity.Phenotypic analyses revealed that overexpression of two of the tRNAs,tK(UUU)and tQ(UUG)could rescue the defects inΔPoelp3 strain.TMT-based proteomic and transcriptional analyses demonstrated that 386 proteins were down-regulated inΔPoelp3 strain compared with wild type strain Guy11,in a transcription-independent manner.Codon usage assays revealed an enrichment of Glutamine CAA-biased mRNA in the 386 proteins compared with the 70-15 genome.In addition to those reported previously,we also found that PoErp9,a sphingolipid C9-methyltransferase,was down-regulated in theΔPoelp3strain.Through an ILV2-specific integration of PoERP9-GFP into the wild type andΔPoelp3 strain,we were able to show that PoErp9 was positively regulated by PoElp3 translationally but not transcriptionally.Functional analyses revealed that PoErp9 was involved in the fungal growth,conidial development,pathogenicity,and TORrelated autophagy homeostasis in Pyricularia oryzae.Taken together,our results suggested that PoElp3 acts through the tRNA-mediated translational efficiency to regulate asexual development,pathogenicity,sphingolipid metabolism,and autophagy in the rice blast fungus.
