P1B-type ATPase ion pumps that transport heavy metal ions across cellular membranes are essential for plant growth and development. To date, a genomic comparison overview of the family in rice, maize and sorghum is no...P1B-type ATPase ion pumps that transport heavy metal ions across cellular membranes are essential for plant growth and development. To date, a genomic comparison overview of the family in rice, maize and sorghum is not yet available. In this study, a total of 31 heavy metal P1B-type ATPase （HMA） genes were identified, including 9 in rice, 11 each from maize and sorghum. They were classified into two distinct subfamilies based on their sequence composition and phylogenetic relationship. Four pairs of HMA genes were expanded via gene duplication with tandemly duplicated. Comprehensive analyses were performed to investigate the expression profiles of HMA genes in various tissues by using quantitative real-time PCR. Some HMA members exhibited abundant and tissue-specific expression patterns. Moreover, most of the genes were found to be differentially expressed under the Cu/Cd treatment. This study will facilitate further studies on P1B-type ATPase family and provide valuable hints for the functional validation in rice, maize and sorghum.展开更多
AIM To observe the changes in erythrocyte membrane ATPases and plasma lipid peroxides (LPO) patients with in abdominal surgery under intravenous procaine-balanced anesthesia.METHODS By determining the ATPase activitie...AIM To observe the changes in erythrocyte membrane ATPases and plasma lipid peroxides (LPO) patients with in abdominal surgery under intravenous procaine-balanced anesthesia.METHODS By determining the ATPase activities of erythrocyte membrane, effects of upper abdominal surgery under intravenous procaine-balanced anesthesia on the function of erythrocytes were observed in 15 patients undergoing cholecystectomy and gastrectomy (5 males and 10 females, aged 45.9±10.20 years and weighed 60.60kg±11.93kg). All patients were free from severe renal, hepatic, pulmonary, cardiac, metabolic and endocrinological diseases and acute infection for at least 2 weeks before surgery. Patients receiving any drug known to affect carbohydrate metabolism prior to anesthesia were excluded from the study.RESULTS Erythrocyte membrane Na+, K+-ATPase, Mg2+-ATPase, Ca2+, Mg2+-ATPase activities were not significantly changed 60min-90min after incision as compared with 30min before anesthesia, but were decreased markedly 10min and 24 hours after completion of operation (P＜0.01). Plasma lipid peroxides (LPO) were increased significantly 24 hours after surgery (P＜0.01) following an initially marked but transient reduction. Plasma LPO changes were not correlated with erythrocyte membrane ATPase activities, r=-0.0396, -0.0097 and 0.4383, respectively (P＞0.05).CONCLUSION Abdominal surgical trauma under intravenous procaine-balanced anesthesia may be associated with the decreased ATPase activities of erythrocyte membrane and increased LPO in plasma.展开更多
Calcium signaling is used by neurons to control a variety of functions,including cellular differentiation,synaptic maturation,neurotransmitter release,intracellular signaling and cell death.This review focuses on one ...Calcium signaling is used by neurons to control a variety of functions,including cellular differentiation,synaptic maturation,neurotransmitter release,intracellular signaling and cell death.This review focuses on one of the most important Ca2+regulators in the cell,the plasma membrane Ca2+-ATPase(PMCA),which has a high affinity for Ca2+and is widely expressed in brain.The ontogeny of PMCA isoforms,linked to specific requirements of Ca2+ during development of different brain areas,is addressed, as well as their function in the adult tissue.This is based on the high diversity of variants in the PMCA family in brain,which show particular kinetic differences possibly related to specific localizations and functions of the cell. Conversely,alterations in the activity of PMCAs could lead to changes in Ca2+homeostasis and,consequently,to neural dysfunction.The involvement of PMCA isoforms in certain neuropathologies and in brain ageing is also discussed.展开更多
Objective:To identify the alleralinn of the membrane polenlial and llie effect of carolenoid extracts from Chlorococcum hnmicola(C.humicola) on membrane hound ATPases and lipid peroxidation.Methods:The lolal carotenoi...Objective:To identify the alleralinn of the membrane polenlial and llie effect of carolenoid extracts from Chlorococcum hnmicola(C.humicola) on membrane hound ATPases and lipid peroxidation.Methods:The lolal carotenoids were extracted from C.humicola.Four groups of Swiss albino mice were treated as control,Benzo(a)pyrene[B(a)P],total carotenoids,B(a)P+ total caralenoids respectively for a period of 60 days.Membrane lipid peroxidation and ATPases(Total ATPases,Ca^(2+)-ATPases.Mg^(2+)-ATPases.Na^+K^+- ATPasei were determined in lung,liver and erythrocyte samples.Results:The activity of lolal ATPase was found to be significantly increased in the B(a)P treated liver and lung tissue.Erythrocyte membrane also showed higher ATPase activity which was significantly reverted on total carolenoid treatment.Conclusions: It can be concluded that the changes in membrane potential favour the functional deterioration of physiological system.The overall findings demonstrates that the animals post treated with carolenoid extract from C.humicola may maintains the alterations in membrane bound ATPase and lipid peroxidation in tissues against the carcinogenic chemical and hence aid in establishing the membrane potential action.Then-fore C.humicola can be further extended to exploits its possible application for various health benefits as neulraceulicals and food additives.展开更多
Background:The increasing incidence of cancers and infectious diseases worldwide presents a significant public health challenge that requires immediate intervention.Our strategy to tackle this issue involves the devel...Background:The increasing incidence of cancers and infectious diseases worldwide presents a significant public health challenge that requires immediate intervention.Our strategy to tackle this issue involves the development of pharmaceutical formulations that combine phytopolyphenols(P),targeted drugs(T),and metal ions(M),collectively referred to as PTM regimens.The diverse pharmacological properties of PTM regimens are hypothesized to effectively reduce the risk factors associated with both cancers and infectious diseases.Methods:The effects of the pharmaceutical agents on the proliferation of cultured cancer cells and pathogens were assessed after 72 h and 48 h,respectively,using the MTT(3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide)assay and optical density at 600 nm(OD600).The synergistic effects of drug combinations were evaluated by combination index(CI),where CI<1 indicates synergism,CI=1 indicates addition,and CI>1 indicates antagonism.Efficacy index(EI)was also calculated.Assays of efflux pump ATPase activities were conducted using a colorimetric method.Results:This study evaluated the anticancer and antibacterial efficacy of PTM regimens that included phytopolyphenols(specifically curcumin(C)and green tea polyphenols(G)),repurposed drugs(memantine(Mem),thioridazine(TRZ),cisplatin(Cis),and 5-fluorouracil(5FU)),and ZnSO_(4)(Zn)across three cultured cancer cell lines and four cultured pathogens.The most effective regimens,GC·Mem·Zn and GC·TRZ·Zn,significantly enhanced the anticancer efficacy(EI)of cisplatin across the three cancer lines(OECM-1,A549 and DLD-1)by 7,11 and 21;7,9,and 17 fold,respectively,while the enhancements for 5-fluorouracil were 5,6 and 12;5,5 and 9 fold,respectively.Furthermore,these PTM regimens demonstrated substantial synergistic inhibition of Na^(+)-K^(+)-Mg^(2+)-ATPase and Mg^(2+)-ATPase in the cultured cancer cells,as well as a reduction in biofilm formation by the four cultured pathogens,suggesting their potential to address the challenges of multidrug resistance in cancers and infectious diseases.Conclusion:Given that all drugs incorporated in the PTM regimens have been clinically validated for safety and efficacy,particularly regarding their synergistic selective anticancer efficacy,inhibition of efflux pump ATPase,and antibiofilm formation of pathogens,these regimens may offer a promising therapeutic strategy to alleviate the severe side effects and drug resistance typically associated with chemotherapeutic agents.Further preclinical and clinical investigations are warranted.展开更多
Chromodomain helicase DNA binding protein 7(CHD7),an ATP-dependent chromatin remodeler,plays versatile roles in neurodevelopment.However,the functional significance of its ATPase/nucleosome remodeling activity remains...Chromodomain helicase DNA binding protein 7(CHD7),an ATP-dependent chromatin remodeler,plays versatile roles in neurodevelopment.However,the functional significance of its ATPase/nucleosome remodeling activity remains incompletely understood.Here,we generate genetically engineered mouse embryonic stem cell lines harboring either an inducible Chd7 knockout or an ATPase-deficient missense variant identified in individuals with CHD7-related disorders.Through in vitro neural induction and differentiation assays combined with mouse brain analyses,we demonstrate that CHD7 enzymatic activity is indispensable for gene regulation and neurite development.Mechanistic studies integrating transcriptomic and epigenomic profiling reveal that CHD7 enzymatic activity is essential for establishing a permissive chromatin landscape at target genes,marked by the open chromatin architecture and active histone modifications.Collectively,our findings underscore the pivotal role of CHD7 enzymatic activity in neurodevelopment and provide critical insights into the pathogenic mechanisms of CHD7 missense variants in human diseases.展开更多
The cell surface receptor chitin elicitor receptor kinase 1(CERK1)is a well-known component of plant immunity.OsCERK1 is involved in regulating copper(Cu)uptake in rice,though the underlying mechanisms remain elusive....The cell surface receptor chitin elicitor receptor kinase 1(CERK1)is a well-known component of plant immunity.OsCERK1 is involved in regulating copper(Cu)uptake in rice,though the underlying mechanisms remain elusive.In this study,we identified proteins interacting with OsCERK1 and uncovered a novel heavy metal-associated domain-containing protein,OsHPP08.Our findings demonstrate that OsCERK1 phosphorylated and stabilized OsHPP08.Through structural analysis using AlphaFold,a yeast sensitivity assay of the Cu uptake-deficient yeast mutant,and Cu level measurements in oshpp08 mutants and overexpression plants(OsHPP08OE),we revealed that OsHPP08 facilitated Cu uptake.Additionally,rice seedling infection assays demonstrated that OsHPP08 positively contributed to blast resistance,with both OsCERK1 and OsHPP08 being essential for Cu-modulated blast resistance.Further analyses suggested that OsCERK1 and OsHPP08 likely enhanced blast resistance by regulating the antioxidant system and increasing H_(2)O_(2) accumulation.In conclusion,OsCERK1 promoted Cu uptake by stabilizing OsHPP08,and together they contributed to Cu-modulated blast resistance,likely through the modulation of reactive oxygen species accumulation.These findings deepen our understanding of the intricate interplay between biotic and abiotic signals in rice.展开更多
Theaflavins from black tea effectively improve insulin secretion in obesity and diabetes,but the molecular mechanisms are unclear.Here,the palmitic acid(PA)-induced pancreaticβ-TC-6 cells and high fat-/high glucose-i...Theaflavins from black tea effectively improve insulin secretion in obesity and diabetes,but the molecular mechanisms are unclear.Here,the palmitic acid(PA)-induced pancreaticβ-TC-6 cells and high fat-/high glucose-induced zebrafish were used.The effects of theaflavin-3,3'-digallate(TF3)on glucolipotoxicityinduced insulin secretion dysfunction,ferroptosis and endoplasmic reticulum(ER)stress were investigated by a variety of molecular biological approaches,inductively coupled plasma-mass spectrometry(ICP-MS),transmission electron microscopy(TEM)and widely targeted metabolomics analysis.TF3 was found to potently inhibit glucolipotoxicity-induced insulin secretion dysfunction and ferroptosis inβ-TC-6 cells and zebrafish,with increasing glutathione peroxidase 4(GPX4)expression,suppressing lipid peroxidation and iron accumulation and protecting mitochondria.Additionally,TF3 attenuated ER stress by regulating 3 unfolded protein response(UPR)pathways inβ-TC-6 cells,and significantly modulated linoleic acid metabolism and L-kynurenine signalling in zebrafish.The expression of sarcoplasmic/endoplasmic reticulum calcium ATPase 2(SERCA2)was obviously enhanced by TF3.Thapsigargin,a SERCA2 inhibitor,remarkably reversed the effects of TF3 on insulin production,ferroptosis,ER stress and the kynurenine signalling.Together,this work revealed the critical role of SERCA2 in ferroptosis regulation,and demonstrated TF3 targeted SERCA2 to inhibit ER stress and ferropto sis,thereby protectingβ-cell secretory function from glucolipotoxicity.展开更多
Host-derived small RNAs are emerging as critical regulators in the dynamic interactions between host tissues and the microbiome,with implications for microbial pathogenesis and host defense.Among these,transfer RNA-de...Host-derived small RNAs are emerging as critical regulators in the dynamic interactions between host tissues and the microbiome,with implications for microbial pathogenesis and host defense.Among these,transfer RNA-derived small RNAs(tsRNAs)have garnered attention for their roles in modulating microbial behavior.However,the bacterial factors mediating tsRNA interaction and functionality remain poorly understood.In this study,using RNA affinity pull-down assay in combination with mass spectrometry,we identified a putative membrane-bound protein,annotated as P-type ATPase transporter(PtaT)in Fusobacterium nucleatum(Fn),which binds Fn-targeting tsRNAs in a sequence-specific manner.Through targeted mutagenesis and phenotypic characterization,we showed that in both the Fn type strain and a clinical tumor isolate,deletion of ptaT led to reduced tsRNA intake and enhanced resistance to tsRNA-induced growth inhibition.Global RNA sequencing and label-free Raman spectroscopy revealed the phenotypic differences between Fn wild type and PtaT-deficient mutant,highlighting the functional significance of PtaT in purine and pyrimidine metabolism.Furthermore,AlphaFold 3 prediction provides evidence supporting the specific binding between PtaT and Fn-targeting tsRNA.By uncovering the first RNA-binding protein in Fn implicated in growth modulation through interactions with host-derived small RNAs(sRNAs),our study offers new insights into sRNA-mediated host-pathogen interplay within the context of microbiome-host interactions.展开更多
BACKGROUND Myocardial infarction(MI)is a significant global cause of chronic heart failure.In post-ischemic cardiac hypertrophy,multiple molecular targets and signals within the cardiac tissue are evident.Mesenchymal ...BACKGROUND Myocardial infarction(MI)is a significant global cause of chronic heart failure.In post-ischemic cardiac hypertrophy,multiple molecular targets and signals within the cardiac tissue are evident.Mesenchymal stem cell-derived exosomes(MSC-EXO)and exercise(EXE)showed promise in enhancing post-ischemic cardiac repair.AIM To investigate how the exosomes released by stem cells and/or EXE can promote cardiac repair and improve isoproterenol(ISO)-induced post-ischemic hypertrophy.METHODS The enrolled animals were divided into 8 control rats and 32 experimental rats.Induction of MI was performed using ISO.Then,the experimental rats were divided into 4 groups:Rats subjected to 4 weeks of swimming EXE,rats treated with exosomes,and the combined treatment.Additionally,functional and interactional exploration of targeted proteins was conducted using Gene Ontology,Kyoto Encyclopedia of Genes and Genomes analysis,and STRING database,along with histological examination.RESULTS Both MSC-EXO or EXE significantly improved ISO induced elevation of cardiac enzymes,oxidative stress,and inflammatory markers,as well as the degenerative changes of the cardiac muscles,fibrosis,and apoptosis.Meanwhile,the combined treatment of EXE and MSC-EXO resulted in a significant improvement in cardiac function and structure as compared to all groups that synchronized with dual inhibition of extracellular signal-regulated kinase and protein kinase B/mammalian target of rapamycin(P<0.01)signaling and modulation of matrix metalloproteinase 9 and sarcoplasmic endoplasmic reticulum calcium ATPase type 2a,with significant improved angiogenesis.CONCLUSION Functional and structural cardiac improvements are accompanied by reduced inflammation,oxidative stress,and apoptosis.Both MSC-EXO and EXE exert cardio-protection by upregulating sarcoplasmic endoplasmic reticulum calcium ATPase,the critical pump for normal calcium handling.展开更多
基金supported by the Special Fund for Agro-Scientific Research in the Public Interest of China(Grant No.201403015)
文摘P1B-type ATPase ion pumps that transport heavy metal ions across cellular membranes are essential for plant growth and development. To date, a genomic comparison overview of the family in rice, maize and sorghum is not yet available. In this study, a total of 31 heavy metal P1B-type ATPase （HMA） genes were identified, including 9 in rice, 11 each from maize and sorghum. They were classified into two distinct subfamilies based on their sequence composition and phylogenetic relationship. Four pairs of HMA genes were expanded via gene duplication with tandemly duplicated. Comprehensive analyses were performed to investigate the expression profiles of HMA genes in various tissues by using quantitative real-time PCR. Some HMA members exhibited abundant and tissue-specific expression patterns. Moreover, most of the genes were found to be differentially expressed under the Cu/Cd treatment. This study will facilitate further studies on P1B-type ATPase family and provide valuable hints for the functional validation in rice, maize and sorghum.
文摘AIM To observe the changes in erythrocyte membrane ATPases and plasma lipid peroxides (LPO) patients with in abdominal surgery under intravenous procaine-balanced anesthesia.METHODS By determining the ATPase activities of erythrocyte membrane, effects of upper abdominal surgery under intravenous procaine-balanced anesthesia on the function of erythrocytes were observed in 15 patients undergoing cholecystectomy and gastrectomy (5 males and 10 females, aged 45.9±10.20 years and weighed 60.60kg±11.93kg). All patients were free from severe renal, hepatic, pulmonary, cardiac, metabolic and endocrinological diseases and acute infection for at least 2 weeks before surgery. Patients receiving any drug known to affect carbohydrate metabolism prior to anesthesia were excluded from the study.RESULTS Erythrocyte membrane Na+, K+-ATPase, Mg2+-ATPase, Ca2+, Mg2+-ATPase activities were not significantly changed 60min-90min after incision as compared with 30min before anesthesia, but were decreased markedly 10min and 24 hours after completion of operation (P＜0.01). Plasma lipid peroxides (LPO) were increased significantly 24 hours after surgery (P＜0.01) following an initially marked but transient reduction. Plasma LPO changes were not correlated with erythrocyte membrane ATPase activities, r=-0.0396, -0.0097 and 0.4383, respectively (P＞0.05).CONCLUSION Abdominal surgical trauma under intravenous procaine-balanced anesthesia may be associated with the decreased ATPase activities of erythrocyte membrane and increased LPO in plasma.
基金Supported by Grants No.BFU2008-00182 from MICINN,Fundación Marcelino Botín,Spain(to Mata AM)Sepulveda MR received a Postdoctoral Fellowship from Programa de Reincorpo-ración de Doctores,Junta de Extremadura,Spain
文摘Calcium signaling is used by neurons to control a variety of functions,including cellular differentiation,synaptic maturation,neurotransmitter release,intracellular signaling and cell death.This review focuses on one of the most important Ca2+regulators in the cell,the plasma membrane Ca2+-ATPase(PMCA),which has a high affinity for Ca2+and is widely expressed in brain.The ontogeny of PMCA isoforms,linked to specific requirements of Ca2+ during development of different brain areas,is addressed, as well as their function in the adult tissue.This is based on the high diversity of variants in the PMCA family in brain,which show particular kinetic differences possibly related to specific localizations and functions of the cell. Conversely,alterations in the activity of PMCAs could lead to changes in Ca2+homeostasis and,consequently,to neural dysfunction.The involvement of PMCA isoforms in certain neuropathologies and in brain ageing is also discussed.
基金Supported by Bharathiar university.coimbatore,Tamilnadu India
文摘Objective:To identify the alleralinn of the membrane polenlial and llie effect of carolenoid extracts from Chlorococcum hnmicola(C.humicola) on membrane hound ATPases and lipid peroxidation.Methods:The lolal carotenoids were extracted from C.humicola.Four groups of Swiss albino mice were treated as control,Benzo(a)pyrene[B(a)P],total carotenoids,B(a)P+ total caralenoids respectively for a period of 60 days.Membrane lipid peroxidation and ATPases(Total ATPases,Ca^(2+)-ATPases.Mg^(2+)-ATPases.Na^+K^+- ATPasei were determined in lung,liver and erythrocyte samples.Results:The activity of lolal ATPase was found to be significantly increased in the B(a)P treated liver and lung tissue.Erythrocyte membrane also showed higher ATPase activity which was significantly reverted on total carolenoid treatment.Conclusions: It can be concluded that the changes in membrane potential favour the functional deterioration of physiological system.The overall findings demonstrates that the animals post treated with carolenoid extract from C.humicola may maintains the alterations in membrane bound ATPase and lipid peroxidation in tissues against the carcinogenic chemical and hence aid in establishing the membrane potential action.Then-fore C.humicola can be further extended to exploits its possible application for various health benefits as neulraceulicals and food additives.
文摘Background:The increasing incidence of cancers and infectious diseases worldwide presents a significant public health challenge that requires immediate intervention.Our strategy to tackle this issue involves the development of pharmaceutical formulations that combine phytopolyphenols(P),targeted drugs(T),and metal ions(M),collectively referred to as PTM regimens.The diverse pharmacological properties of PTM regimens are hypothesized to effectively reduce the risk factors associated with both cancers and infectious diseases.Methods:The effects of the pharmaceutical agents on the proliferation of cultured cancer cells and pathogens were assessed after 72 h and 48 h,respectively,using the MTT(3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide)assay and optical density at 600 nm(OD600).The synergistic effects of drug combinations were evaluated by combination index(CI),where CI<1 indicates synergism,CI=1 indicates addition,and CI>1 indicates antagonism.Efficacy index(EI)was also calculated.Assays of efflux pump ATPase activities were conducted using a colorimetric method.Results:This study evaluated the anticancer and antibacterial efficacy of PTM regimens that included phytopolyphenols(specifically curcumin(C)and green tea polyphenols(G)),repurposed drugs(memantine(Mem),thioridazine(TRZ),cisplatin(Cis),and 5-fluorouracil(5FU)),and ZnSO_(4)(Zn)across three cultured cancer cell lines and four cultured pathogens.The most effective regimens,GC·Mem·Zn and GC·TRZ·Zn,significantly enhanced the anticancer efficacy(EI)of cisplatin across the three cancer lines(OECM-1,A549 and DLD-1)by 7,11 and 21;7,9,and 17 fold,respectively,while the enhancements for 5-fluorouracil were 5,6 and 12;5,5 and 9 fold,respectively.Furthermore,these PTM regimens demonstrated substantial synergistic inhibition of Na^(+)-K^(+)-Mg^(2+)-ATPase and Mg^(2+)-ATPase in the cultured cancer cells,as well as a reduction in biofilm formation by the four cultured pathogens,suggesting their potential to address the challenges of multidrug resistance in cancers and infectious diseases.Conclusion:Given that all drugs incorporated in the PTM regimens have been clinically validated for safety and efficacy,particularly regarding their synergistic selective anticancer efficacy,inhibition of efflux pump ATPase,and antibiofilm formation of pathogens,these regimens may offer a promising therapeutic strategy to alleviate the severe side effects and drug resistance typically associated with chemotherapeutic agents.Further preclinical and clinical investigations are warranted.
基金supported by the Medical Science Data Center at Shanghai Medical College of Fudan Universitysupported by grants from National Natural Science Foundation of China (81974229and 82171167 to W.F.,82330049 to W.Z.)+2 种基金Xiamen Municipal Major Project of High-Quality Development of Health and Wellness Technology Program (2024-GZL-GD06 to W.F.)National Key R&D Program of China (2022YFA0806603 to W.F.)Science and Technology Program of Guangzhou,China (2024A04J4924 to C.H.)
文摘Chromodomain helicase DNA binding protein 7(CHD7),an ATP-dependent chromatin remodeler,plays versatile roles in neurodevelopment.However,the functional significance of its ATPase/nucleosome remodeling activity remains incompletely understood.Here,we generate genetically engineered mouse embryonic stem cell lines harboring either an inducible Chd7 knockout or an ATPase-deficient missense variant identified in individuals with CHD7-related disorders.Through in vitro neural induction and differentiation assays combined with mouse brain analyses,we demonstrate that CHD7 enzymatic activity is indispensable for gene regulation and neurite development.Mechanistic studies integrating transcriptomic and epigenomic profiling reveal that CHD7 enzymatic activity is essential for establishing a permissive chromatin landscape at target genes,marked by the open chromatin architecture and active histone modifications.Collectively,our findings underscore the pivotal role of CHD7 enzymatic activity in neurodevelopment and provide critical insights into the pathogenic mechanisms of CHD7 missense variants in human diseases.
基金supported by the Zhejiang Provincial Natural Science Foundation of China(Grant Nos.LR24C140001 and LZ23C130002)the National Natural Science Foundation of China(Grant No.U23A20178)the Innovation Program of the Chinese Academy of Agricultural Sciences(Grant Nos.Y2023QC22 and CAAS-CSCB-202301).
文摘The cell surface receptor chitin elicitor receptor kinase 1(CERK1)is a well-known component of plant immunity.OsCERK1 is involved in regulating copper(Cu)uptake in rice,though the underlying mechanisms remain elusive.In this study,we identified proteins interacting with OsCERK1 and uncovered a novel heavy metal-associated domain-containing protein,OsHPP08.Our findings demonstrate that OsCERK1 phosphorylated and stabilized OsHPP08.Through structural analysis using AlphaFold,a yeast sensitivity assay of the Cu uptake-deficient yeast mutant,and Cu level measurements in oshpp08 mutants and overexpression plants(OsHPP08OE),we revealed that OsHPP08 facilitated Cu uptake.Additionally,rice seedling infection assays demonstrated that OsHPP08 positively contributed to blast resistance,with both OsCERK1 and OsHPP08 being essential for Cu-modulated blast resistance.Further analyses suggested that OsCERK1 and OsHPP08 likely enhanced blast resistance by regulating the antioxidant system and increasing H_(2)O_(2) accumulation.In conclusion,OsCERK1 promoted Cu uptake by stabilizing OsHPP08,and together they contributed to Cu-modulated blast resistance,likely through the modulation of reactive oxygen species accumulation.These findings deepen our understanding of the intricate interplay between biotic and abiotic signals in rice.
基金supported by National Natural Science Foundation of China(32272303)Natural Science Foundation of Zhejiang Province,China(LY21C200010)。
文摘Theaflavins from black tea effectively improve insulin secretion in obesity and diabetes,but the molecular mechanisms are unclear.Here,the palmitic acid(PA)-induced pancreaticβ-TC-6 cells and high fat-/high glucose-induced zebrafish were used.The effects of theaflavin-3,3'-digallate(TF3)on glucolipotoxicityinduced insulin secretion dysfunction,ferroptosis and endoplasmic reticulum(ER)stress were investigated by a variety of molecular biological approaches,inductively coupled plasma-mass spectrometry(ICP-MS),transmission electron microscopy(TEM)and widely targeted metabolomics analysis.TF3 was found to potently inhibit glucolipotoxicity-induced insulin secretion dysfunction and ferroptosis inβ-TC-6 cells and zebrafish,with increasing glutathione peroxidase 4(GPX4)expression,suppressing lipid peroxidation and iron accumulation and protecting mitochondria.Additionally,TF3 attenuated ER stress by regulating 3 unfolded protein response(UPR)pathways inβ-TC-6 cells,and significantly modulated linoleic acid metabolism and L-kynurenine signalling in zebrafish.The expression of sarcoplasmic/endoplasmic reticulum calcium ATPase 2(SERCA2)was obviously enhanced by TF3.Thapsigargin,a SERCA2 inhibitor,remarkably reversed the effects of TF3 on insulin production,ferroptosis,ER stress and the kynurenine signalling.Together,this work revealed the critical role of SERCA2 in ferroptosis regulation,and demonstrated TF3 targeted SERCA2 to inhibit ER stress and ferropto sis,thereby protectingβ-cell secretory function from glucolipotoxicity.
基金supported by NSF 2333230 (J.L.),NIH National Institute of Dental and Craniofacial Research (NIDCR) awards,DE030943 (X.H.),DE023810 (X.H.) and DE031329 (J.L.),T90 DE026110,and K99 DE033794 (to P.-T.D.)
文摘Host-derived small RNAs are emerging as critical regulators in the dynamic interactions between host tissues and the microbiome,with implications for microbial pathogenesis and host defense.Among these,transfer RNA-derived small RNAs(tsRNAs)have garnered attention for their roles in modulating microbial behavior.However,the bacterial factors mediating tsRNA interaction and functionality remain poorly understood.In this study,using RNA affinity pull-down assay in combination with mass spectrometry,we identified a putative membrane-bound protein,annotated as P-type ATPase transporter(PtaT)in Fusobacterium nucleatum(Fn),which binds Fn-targeting tsRNAs in a sequence-specific manner.Through targeted mutagenesis and phenotypic characterization,we showed that in both the Fn type strain and a clinical tumor isolate,deletion of ptaT led to reduced tsRNA intake and enhanced resistance to tsRNA-induced growth inhibition.Global RNA sequencing and label-free Raman spectroscopy revealed the phenotypic differences between Fn wild type and PtaT-deficient mutant,highlighting the functional significance of PtaT in purine and pyrimidine metabolism.Furthermore,AlphaFold 3 prediction provides evidence supporting the specific binding between PtaT and Fn-targeting tsRNA.By uncovering the first RNA-binding protein in Fn implicated in growth modulation through interactions with host-derived small RNAs(sRNAs),our study offers new insights into sRNA-mediated host-pathogen interplay within the context of microbiome-host interactions.
文摘BACKGROUND Myocardial infarction(MI)is a significant global cause of chronic heart failure.In post-ischemic cardiac hypertrophy,multiple molecular targets and signals within the cardiac tissue are evident.Mesenchymal stem cell-derived exosomes(MSC-EXO)and exercise(EXE)showed promise in enhancing post-ischemic cardiac repair.AIM To investigate how the exosomes released by stem cells and/or EXE can promote cardiac repair and improve isoproterenol(ISO)-induced post-ischemic hypertrophy.METHODS The enrolled animals were divided into 8 control rats and 32 experimental rats.Induction of MI was performed using ISO.Then,the experimental rats were divided into 4 groups:Rats subjected to 4 weeks of swimming EXE,rats treated with exosomes,and the combined treatment.Additionally,functional and interactional exploration of targeted proteins was conducted using Gene Ontology,Kyoto Encyclopedia of Genes and Genomes analysis,and STRING database,along with histological examination.RESULTS Both MSC-EXO or EXE significantly improved ISO induced elevation of cardiac enzymes,oxidative stress,and inflammatory markers,as well as the degenerative changes of the cardiac muscles,fibrosis,and apoptosis.Meanwhile,the combined treatment of EXE and MSC-EXO resulted in a significant improvement in cardiac function and structure as compared to all groups that synchronized with dual inhibition of extracellular signal-regulated kinase and protein kinase B/mammalian target of rapamycin(P<0.01)signaling and modulation of matrix metalloproteinase 9 and sarcoplasmic endoplasmic reticulum calcium ATPase type 2a,with significant improved angiogenesis.CONCLUSION Functional and structural cardiac improvements are accompanied by reduced inflammation,oxidative stress,and apoptosis.Both MSC-EXO and EXE exert cardio-protection by upregulating sarcoplasmic endoplasmic reticulum calcium ATPase,the critical pump for normal calcium handling.
