A ratiometric fluorescent hybrid nanoprobe CDs-1 for arginine(Arg),exhibiting high sensitivity(the limit of detection,LOD,being 6.5×10^-8 mol/L) and excellent selectivity and anti-interference ability,was fabrica...A ratiometric fluorescent hybrid nanoprobe CDs-1 for arginine(Arg),exhibiting high sensitivity(the limit of detection,LOD,being 6.5×10^-8 mol/L) and excellent selectivity and anti-interference ability,was fabricated through fluorescence resonance energy transfer(FRET) and the electrostatic attraction between positively-charged hemicyanine molecules and negatively-charged carbon dots(CDs).Arg can be quantitatively detected in the concentration range from 6.0×10^-5 mol/L to 2.7×10^-4 mol/L.Further,due to its ability to target mitochondrion and low cytotoxicity,intracellular Arg was succes s fully tracked through ratiometric fluorescence imaging.展开更多
Hypochlorite anion is a ubiquitous reactive molecule in the terminal disinfection systems, inflammatory stress and immune systems. Thus, rapid and visual monitoring ClO^- in water and biological samples is very meanin...Hypochlorite anion is a ubiquitous reactive molecule in the terminal disinfection systems, inflammatory stress and immune systems. Thus, rapid and visual monitoring ClO^- in water and biological samples is very meaningful for water quality safety and toxicity assessment of contaminants. Herein, a colorimetric and fluorometric probe（Rh-ClO） based on rhodamine B fluorophore and thiophene-2-carbohydrazide has been unveiled and successfully utilized for ClO^- detection in water samples and HeLa cells. Upon addition of ClO^-, color changes of solution from colorless to pink were immediately visible to the nakedeyes, meanwhile, brilliant red fluorescence was observed under excited at UV light（365 nm）. Rh-ClO displayed high selectivity and sensitivity for ClO^- , and the detection limit was 7 mmol/L calculated from the fluorescence titration. With the aid of its merits including rapid response to ClO^- within 10 s, Rh-ClO and its test paper could successfully detect ClO^- in water. Additionally, HeLa cells image co-stained with Rh-ClO and Rh123 demonstrated that Rh-ClO possessed excellent and fast cell-membrane permeability and mitochondrion-targetability. It was clearly confirmed that Rh-ClO would be a promising probe for rapid tracking of ClO^- in water samples and in mitochondria of living cells.展开更多
Apoptosis plays an important role in the pathogenesis of viral infections.In this study,we investigated the cell death processes during productive HHV-6A infection and the underlying mechanisms.Annexin V-PI staining a...Apoptosis plays an important role in the pathogenesis of viral infections.In this study,we investigated the cell death processes during productive HHV-6A infection and the underlying mechanisms.Annexin V-PI staining and electron microscopy indicated that HHV-6A is a strong inducer of apoptosis.HHV-6A infection decreased mitochondrial transmembrane potential and led to morphological changes of mitochondria.The cell death was associated with activation of caspase-3 and cleavage of DNA repair enzyme poly （ADP-ribose） polymerase,which is known to be an important substrate for activated caspase-3.Caspase-9 was activated significantly in HHV-6A-infected cells,whereas caspase-8 was not activated obviously.Moreover,HHV-6A infection upregulated Bax and downregulated Bcl-2.This is the first demonstration of mitochondrion-mediated,caspase-dependent apoptosis in HHV-6A-infected cells.展开更多
Transmission electron microscopy of the yellowfin porgy (Sparus latus Houttuyn) spermatozoa ultrastructure showed the spermatozoon as a primitive type made up of the acrosomeless head , the flagellum , and the midpiec...Transmission electron microscopy of the yellowfin porgy (Sparus latus Houttuyn) spermatozoa ultrastructure showed the spermatozoon as a primitive type made up of the acrosomeless head , the flagellum , and the midpiece , at the periphery of which was a relatively big mitochondrion with more complex structure . It was found that during spermiogenesis, only one relatively big mitochondrion occurred in both the spermatid and the spermatozoon . This is different from other teleost fishes . During spermiogenesis, the mitochondria number is one, and morphology did not change . All these are different fromthose of other fishes .展开更多
Microglia are the first immune cells that are activated in the brain following ischemic stroke.Mitochondrial dysfunction exacerbates microglia-mediated neuroinflammation post-stroke.Caspase activation and recruitment ...Microglia are the first immune cells that are activated in the brain following ischemic stroke.Mitochondrial dysfunction exacerbates microglia-mediated neuroinflammation post-stroke.Caspase activation and recruitment domain 19(CARD19)is involved in innate immune response and inflammatory response,which are also important functions of microglia.However,the role of CARD19 in microglial biology and ischemic stroke remains unknown.Here,we observed that CARD19 expression was significantly elevated in microglia in the penumbra after ischemic stroke via analyzing the spatial transcriptomic sequencing data of ischemic brain tissue,as well as in an in vitro model of microglial activation.Remarkably,conditional knockdown of Card19 in microglia promoted post-stroke neuroinflammation and worsened neurological outcomes in a mouse model of ischemic stroke.Mechanistically,we found that CARD19 localized to mitochondria and promoted the assembly of mitochondrial intermembrane bridge components,while CARD19 deficiency in microglia caused ultrastructural and functional damage to the mitochondrial cristae,leading to an exaggerated pro-inflammatory response.Thus,our findings suggest that preserving mitochondrial cristae,by targeting CARD19 could be a novel therapeutic strategy for ameliorating neuroinflammation post-stroke and decreasing the volume of the ischemic penumbra.展开更多
Background This study investigated the molecular mechanisms by which redox status regulates protoporphyrin IX(PpIX)biosynthesis and eggshell coloration in brown-shelled laying hens.This study consisted of two experime...Background This study investigated the molecular mechanisms by which redox status regulates protoporphyrin IX(PpIX)biosynthesis and eggshell coloration in brown-shelled laying hens.This study consisted of two experiments involving 48 and 32 healthy 60-week-old Hy-Line Brown hens,respectively.The hens exhibited either dark(L*=51.99±2.08)or light(L*=64.12±3.02)brown eggshell colors.In Exp.1,light brown-shelled hens were fed a basal diet(Lb group),while dark brown-shelled hens received either a basal diet(Db group)or a basal diet with 10 mg/kg ammonium metavanadate(Dbv group)for 20 d.In Exp.2,light brown-shelled hens received either a basal diet(Lbc group)or a basal diet supplemented with 200 mg/kg resveratrol(Lbr group)for 12 weeks.Results Compared to the Db group,eggshell L*values increased,and PpIX concentrations in both eggshell and uterus decreased in Dbv and Lb groups.These groups also showed oxidative stress,as indicated by reduced hepatic T-SOD and CAT activities.Uterine redox status changes were further confirmed by increased T-AOC level(Dbv)and reduced CAT gene expression(Lb).These redox disturbances led to reduced expression of ND4 and COX1 mt DNA,decreased ATP production and CS activity,along with upregulation of IR,PI3K,HK,and PK gene expression,reflecting altered mitochondrial energy metabolism.Notably,the SIRT1/PGC-1αsignaling cascade and its downstream target ALAS1 were significantly downregulated at both mRNA and protein levels in Dbv and Lb groups.Compared to the Lbc group,the Lbr group exhibited higher antioxidant capacity by increasing hepatic CAT activity and uterine T-SOD and GSH-Px activities,and reducing MDA levels.Moreover,the Lbr group restored mitochondrial function and PpIX biosynthesis by upregulating ND4 and COX1 mt DNA,CS and SDHA gene expression,and SIRT1/PGC-1α/ALAS1 signaling,while downregulating LDH activity and the expression of IR and PI3K,thereby alleviating eggshell color fading.Conclusion Oxidative stress induces eggshell depigmentation by impairing mitochondrial function and downregulating the SIRT1/PGC-1α/ALAS1 pathway,leading to reduced PpIX biosynthesis.Specifically,vanadium-induced or endogenous oxidative stress disrupts mitochondrial energy metabolism and suppresses key components of this pathway,while resveratrol alleviates oxidative damage and restores mitochondrial function and ALAS1-driven PpIX synthesis through reactivation of the SIRT1/PGC-1αaxis.展开更多
In many organisms, the difference in codon usage patterns among genes reflects variation in local base compositional biases and the intensity of natural selection. In this study, a comparative analysis was performed t...In many organisms, the difference in codon usage patterns among genes reflects variation in local base compositional biases and the intensity of natural selection. In this study, a comparative analysis was performed to investigate the characteristics of codon bias and factors in shaping the codon usage patterns among mitochondrion, chloroplast and nuclear genes in common wheat （Triticum aestivum L.）. GC contents in nuclear genes were higher than that in mitochondrion and chloroplast genes. The neutrality and correspondence analyses indicated that the codon usage in nuclear genes would be a result of relative strong mutational bias, while the codon usage patterns of mitochondrion and chloroplast genes were more conserved in GC content and influenced by translation level. The Parity Rule 2 （PR2） plot analysis showed that pyrimidines were used more frequently than purines at the third codon position in the three genomes. In addition, using a new alterative strategy, 11, 12, and 24 triplets were defined as preferred codons in the mitochondrion, chloroplast and nuclear genes, respectively. These findings suggested that the mitochondrion, chloroplast and nuclear genes shared particularly different features of codon usage and evolutionary constraints.展开更多
Study of nitrogen-fixation cell biology has gradually advanced to the study of only one kind of cells in root nodules, such as the infected cell, uninfected cell, cortex cell, from general structure of root nodules no...Study of nitrogen-fixation cell biology has gradually advanced to the study of only one kind of cells in root nodules, such as the infected cell, uninfected cell, cortex cell, from general structure of root nodules now. Some authors even start to study one kind of composition of the above-mentioned cells, for example, cell wall, cytoplasm, dictyosome, microbody and specially cytoplasmic inclusion, etc., because these studies can help us展开更多
The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular an...The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.展开更多
Chronic hypoxia is a key factor in the pathogenesis of cardiovascular diseases,including ischemia,heart failure,and hypertension.Under hypoxia,oxygen deficiency disrupts oxidative phosphorylation in mitochondria,impai...Chronic hypoxia is a key factor in the pathogenesis of cardiovascular diseases,including ischemia,heart failure,and hypertension.Under hypoxia,oxygen deficiency disrupts oxidative phosphorylation in mitochondria,impairing ATP production and generating reactive oxygen species(ROS).These reactive species induce mitochondrial dysfunction,leading to oxidative stress,calcium imbalance,and activation of apoptosis pathways.The mitochondrial ATP-sensitive potassium channel(mitoKATP)and mitochondrial permeability transition pore(mPTP)channels are particularly affected,contributing to membrane potential loss,cytochrome c release,and cell death.This review delves into the molecular mechanisms underlying hypoxia-induced cardiovascular diseases,with a focus on mitochondrial impairment,ion channel dysfunction,and ROS overproduction.Additionally,we examine hypoxia-inducible factor 1-alpha(HIF-1α)as a biomarker of cellular adaptation and discuss therapeutic strategies targeting mitochondrial function and oxidative stress.Antioxidants and compounds modulating key ion channels,such as mitoKATP and mPTP,are highlighted as promising interventions for mitigating hypoxia-induced damage.Furthermore,we emphasize the potential of integrating in vitro,in vivo,and in silico studies to develop novel therapies aimed at preserving mitochondrial integrity and preventing cardiovascular diseases.展开更多
Pentatricopeptide repeat(PPR)proteins are a large group of eukaryote-specific RNA-binding proteins that play pivotal roles in plant organelle gene expression.Here,we report the function of PPR21 in mitochondrial intro...Pentatricopeptide repeat(PPR)proteins are a large group of eukaryote-specific RNA-binding proteins that play pivotal roles in plant organelle gene expression.Here,we report the function of PPR21 in mitochondrial intron splicing and its role in maize kernel development.PPR21 is a typical P-type PPR protein targeted to mitochondria.The ppr21 mutants are arrested in embryogenesis and endosperm development,leading to embryo lethality.Null mutations of PPR21 reduce the splicing efficiency of nad2 intron 1,2,and 4 and impair the assembly and activity of mitochondrial complex I.Previous studies show that the P-type PPR protein EMP12 is required for the splicing of identical introns.However,our protein interaction analyses reveal that PPR21 does not interact with EMP12.Instead,both PPR21 and EMP12 interact with the small MutS-related(SMR)domain-containing PPR protein 1(PPR-SMR1)and the short P-type PPR protein 2(SPR2).PPR-SMR1 interacts with SPR2,and both proteins are required for the splicing of many introns in mitochondria,including nad2 intron 1,2,and 4.These results suggest that a PPR21-(PPR-SMR1/SPR2)-EMP12 complex is involved in the splicing of nad2 introns in maize mitochondria.展开更多
Male gametes are produced in the anthers and are essential for fertilization and seed setting.A transverse section of the anther reveals four layers:the epidermis,endothecium,middle layer,and tapetum.The tapetum,being...Male gametes are produced in the anthers and are essential for fertilization and seed setting.A transverse section of the anther reveals four layers:the epidermis,endothecium,middle layer,and tapetum.The tapetum,being the innermost layer,plays a critical role in supplying nutrients,enzymes,and protection to microspores.Detailed microscopic and ultrastructural analyses have revealed highly active and well-organized structures within the tapetum,referred to as tapetal organelles.Molecular studies have highlighted the significance of tapetal cell death and the nurturing role of the tapetum for microspores.However,the mechanisms by which these processes are mediated by tapetal organelles at the cellular level remain elusive.The discovery of mutants defective in tapetal organelles has enabled further investigations into their structure,morphology,and function.This review discusses the molecular and functional roles of various tapetal organelles,such as plastids(amyloplasts and elaioplasts),mitochondria,tapetosomes,endoplasmic reticulum,and lipid bodies.We provide an overview of their roles,highlight key organelles in the tapetum,and address recent challenges and potential applications of genes regulating tapetal organelles in enhancing crop fertility.展开更多
基金National Natural Science Foundation of China(Nos.U1704161,U1504203,21601158)Zhengzhou University(No.32210431)for the financial supports。
文摘A ratiometric fluorescent hybrid nanoprobe CDs-1 for arginine(Arg),exhibiting high sensitivity(the limit of detection,LOD,being 6.5×10^-8 mol/L) and excellent selectivity and anti-interference ability,was fabricated through fluorescence resonance energy transfer(FRET) and the electrostatic attraction between positively-charged hemicyanine molecules and negatively-charged carbon dots(CDs).Arg can be quantitatively detected in the concentration range from 6.0×10^-5 mol/L to 2.7×10^-4 mol/L.Further,due to its ability to target mitochondrion and low cytotoxicity,intracellular Arg was succes s fully tracked through ratiometric fluorescence imaging.
基金supported by the National Natural Science Foundation of China (No. 21302080)Program Funded by Liaoning Province Education Administration (No. L2014010)
文摘Hypochlorite anion is a ubiquitous reactive molecule in the terminal disinfection systems, inflammatory stress and immune systems. Thus, rapid and visual monitoring ClO^- in water and biological samples is very meaningful for water quality safety and toxicity assessment of contaminants. Herein, a colorimetric and fluorometric probe（Rh-ClO） based on rhodamine B fluorophore and thiophene-2-carbohydrazide has been unveiled and successfully utilized for ClO^- detection in water samples and HeLa cells. Upon addition of ClO^-, color changes of solution from colorless to pink were immediately visible to the nakedeyes, meanwhile, brilliant red fluorescence was observed under excited at UV light（365 nm）. Rh-ClO displayed high selectivity and sensitivity for ClO^- , and the detection limit was 7 mmol/L calculated from the fluorescence titration. With the aid of its merits including rapid response to ClO^- within 10 s, Rh-ClO and its test paper could successfully detect ClO^- in water. Additionally, HeLa cells image co-stained with Rh-ClO and Rh123 demonstrated that Rh-ClO possessed excellent and fast cell-membrane permeability and mitochondrion-targetability. It was clearly confirmed that Rh-ClO would be a promising probe for rapid tracking of ClO^- in water samples and in mitochondria of living cells.
基金supported by the National Natural Science Foundationof China (No. 30771961 and No. 30901344)Science Development Foundation of Nanjing Medical University (No. 08NMUZ003)Jiangsu Province Laboratory of Pathogen Biology (No. 08bykf01)
文摘Apoptosis plays an important role in the pathogenesis of viral infections.In this study,we investigated the cell death processes during productive HHV-6A infection and the underlying mechanisms.Annexin V-PI staining and electron microscopy indicated that HHV-6A is a strong inducer of apoptosis.HHV-6A infection decreased mitochondrial transmembrane potential and led to morphological changes of mitochondria.The cell death was associated with activation of caspase-3 and cleavage of DNA repair enzyme poly （ADP-ribose） polymerase,which is known to be an important substrate for activated caspase-3.Caspase-9 was activated significantly in HHV-6A-infected cells,whereas caspase-8 was not activated obviously.Moreover,HHV-6A infection upregulated Bax and downregulated Bcl-2.This is the first demonstration of mitochondrion-mediated,caspase-dependent apoptosis in HHV-6A-infected cells.
文摘Transmission electron microscopy of the yellowfin porgy (Sparus latus Houttuyn) spermatozoa ultrastructure showed the spermatozoon as a primitive type made up of the acrosomeless head , the flagellum , and the midpiece , at the periphery of which was a relatively big mitochondrion with more complex structure . It was found that during spermiogenesis, only one relatively big mitochondrion occurred in both the spermatid and the spermatozoon . This is different from other teleost fishes . During spermiogenesis, the mitochondria number is one, and morphology did not change . All these are different fromthose of other fishes .
基金National Natural Science Foundation of China,Nos.81920108017(to YX),82401546(to HL)Jiangsu Province Key Medical Discipline,No.ZDXK202216(to YX)the Key Research and Development Program of Jiangsu Province of China,No.BE2020620(to YX).
文摘Microglia are the first immune cells that are activated in the brain following ischemic stroke.Mitochondrial dysfunction exacerbates microglia-mediated neuroinflammation post-stroke.Caspase activation and recruitment domain 19(CARD19)is involved in innate immune response and inflammatory response,which are also important functions of microglia.However,the role of CARD19 in microglial biology and ischemic stroke remains unknown.Here,we observed that CARD19 expression was significantly elevated in microglia in the penumbra after ischemic stroke via analyzing the spatial transcriptomic sequencing data of ischemic brain tissue,as well as in an in vitro model of microglial activation.Remarkably,conditional knockdown of Card19 in microglia promoted post-stroke neuroinflammation and worsened neurological outcomes in a mouse model of ischemic stroke.Mechanistically,we found that CARD19 localized to mitochondria and promoted the assembly of mitochondrial intermembrane bridge components,while CARD19 deficiency in microglia caused ultrastructural and functional damage to the mitochondrial cristae,leading to an exaggerated pro-inflammatory response.Thus,our findings suggest that preserving mitochondrial cristae,by targeting CARD19 could be a novel therapeutic strategy for ameliorating neuroinflammation post-stroke and decreasing the volume of the ischemic penumbra.
基金financially supported by the National Natural Science Foundation of China(32322078)the earmarked fund for the China Agriculture Research System(CARS-40)+1 种基金the China Postdoctoral Science Foundation(grant no.2024M763615)the Agricultural Science and Technology Innovation Program(ASTIP)of CAAS。
文摘Background This study investigated the molecular mechanisms by which redox status regulates protoporphyrin IX(PpIX)biosynthesis and eggshell coloration in brown-shelled laying hens.This study consisted of two experiments involving 48 and 32 healthy 60-week-old Hy-Line Brown hens,respectively.The hens exhibited either dark(L*=51.99±2.08)or light(L*=64.12±3.02)brown eggshell colors.In Exp.1,light brown-shelled hens were fed a basal diet(Lb group),while dark brown-shelled hens received either a basal diet(Db group)or a basal diet with 10 mg/kg ammonium metavanadate(Dbv group)for 20 d.In Exp.2,light brown-shelled hens received either a basal diet(Lbc group)or a basal diet supplemented with 200 mg/kg resveratrol(Lbr group)for 12 weeks.Results Compared to the Db group,eggshell L*values increased,and PpIX concentrations in both eggshell and uterus decreased in Dbv and Lb groups.These groups also showed oxidative stress,as indicated by reduced hepatic T-SOD and CAT activities.Uterine redox status changes were further confirmed by increased T-AOC level(Dbv)and reduced CAT gene expression(Lb).These redox disturbances led to reduced expression of ND4 and COX1 mt DNA,decreased ATP production and CS activity,along with upregulation of IR,PI3K,HK,and PK gene expression,reflecting altered mitochondrial energy metabolism.Notably,the SIRT1/PGC-1αsignaling cascade and its downstream target ALAS1 were significantly downregulated at both mRNA and protein levels in Dbv and Lb groups.Compared to the Lbc group,the Lbr group exhibited higher antioxidant capacity by increasing hepatic CAT activity and uterine T-SOD and GSH-Px activities,and reducing MDA levels.Moreover,the Lbr group restored mitochondrial function and PpIX biosynthesis by upregulating ND4 and COX1 mt DNA,CS and SDHA gene expression,and SIRT1/PGC-1α/ALAS1 signaling,while downregulating LDH activity and the expression of IR and PI3K,thereby alleviating eggshell color fading.Conclusion Oxidative stress induces eggshell depigmentation by impairing mitochondrial function and downregulating the SIRT1/PGC-1α/ALAS1 pathway,leading to reduced PpIX biosynthesis.Specifically,vanadium-induced or endogenous oxidative stress disrupts mitochondrial energy metabolism and suppresses key components of this pathway,while resveratrol alleviates oxidative damage and restores mitochondrial function and ALAS1-driven PpIX synthesis through reactivation of the SIRT1/PGC-1αaxis.
基金Supported by the Sate Key Basic Research and Development Plan of China （2003CB715904） and the National Science Foundation for 0verseas Distinguished Young Scholar （30428003）
文摘In many organisms, the difference in codon usage patterns among genes reflects variation in local base compositional biases and the intensity of natural selection. In this study, a comparative analysis was performed to investigate the characteristics of codon bias and factors in shaping the codon usage patterns among mitochondrion, chloroplast and nuclear genes in common wheat （Triticum aestivum L.）. GC contents in nuclear genes were higher than that in mitochondrion and chloroplast genes. The neutrality and correspondence analyses indicated that the codon usage in nuclear genes would be a result of relative strong mutational bias, while the codon usage patterns of mitochondrion and chloroplast genes were more conserved in GC content and influenced by translation level. The Parity Rule 2 （PR2） plot analysis showed that pyrimidines were used more frequently than purines at the third codon position in the three genomes. In addition, using a new alterative strategy, 11, 12, and 24 triplets were defined as preferred codons in the mitochondrion, chloroplast and nuclear genes, respectively. These findings suggested that the mitochondrion, chloroplast and nuclear genes shared particularly different features of codon usage and evolutionary constraints.
文摘Study of nitrogen-fixation cell biology has gradually advanced to the study of only one kind of cells in root nodules, such as the infected cell, uninfected cell, cortex cell, from general structure of root nodules now. Some authors even start to study one kind of composition of the above-mentioned cells, for example, cell wall, cytoplasm, dictyosome, microbody and specially cytoplasmic inclusion, etc., because these studies can help us
基金supported by the National Natural Science Foundation of China,Nos.82271327 (to ZW),82072535 (to ZW),81873768 (to ZW),and 82001253 (to TL)。
文摘The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.
基金supported by"Potential Medicinal Plants of Uzbekistan with Adaptogenic Effects and Their Molecular,Cellular,and Therapeutic Mechanisms"from the Innovative Development Agency under the Ministry of Higher Education,Science,and Innovation of the Republic of Uzbekistan(Grant No.FL-8323102109).
文摘Chronic hypoxia is a key factor in the pathogenesis of cardiovascular diseases,including ischemia,heart failure,and hypertension.Under hypoxia,oxygen deficiency disrupts oxidative phosphorylation in mitochondria,impairing ATP production and generating reactive oxygen species(ROS).These reactive species induce mitochondrial dysfunction,leading to oxidative stress,calcium imbalance,and activation of apoptosis pathways.The mitochondrial ATP-sensitive potassium channel(mitoKATP)and mitochondrial permeability transition pore(mPTP)channels are particularly affected,contributing to membrane potential loss,cytochrome c release,and cell death.This review delves into the molecular mechanisms underlying hypoxia-induced cardiovascular diseases,with a focus on mitochondrial impairment,ion channel dysfunction,and ROS overproduction.Additionally,we examine hypoxia-inducible factor 1-alpha(HIF-1α)as a biomarker of cellular adaptation and discuss therapeutic strategies targeting mitochondrial function and oxidative stress.Antioxidants and compounds modulating key ion channels,such as mitoKATP and mPTP,are highlighted as promising interventions for mitigating hypoxia-induced damage.Furthermore,we emphasize the potential of integrating in vitro,in vivo,and in silico studies to develop novel therapies aimed at preserving mitochondrial integrity and preventing cardiovascular diseases.
基金supported by the National Natural Science Foundation of China(32072126 and 32230075)the Shandong Provincial Natural Science Foundation(ZR2019MC005).
文摘Pentatricopeptide repeat(PPR)proteins are a large group of eukaryote-specific RNA-binding proteins that play pivotal roles in plant organelle gene expression.Here,we report the function of PPR21 in mitochondrial intron splicing and its role in maize kernel development.PPR21 is a typical P-type PPR protein targeted to mitochondria.The ppr21 mutants are arrested in embryogenesis and endosperm development,leading to embryo lethality.Null mutations of PPR21 reduce the splicing efficiency of nad2 intron 1,2,and 4 and impair the assembly and activity of mitochondrial complex I.Previous studies show that the P-type PPR protein EMP12 is required for the splicing of identical introns.However,our protein interaction analyses reveal that PPR21 does not interact with EMP12.Instead,both PPR21 and EMP12 interact with the small MutS-related(SMR)domain-containing PPR protein 1(PPR-SMR1)and the short P-type PPR protein 2(SPR2).PPR-SMR1 interacts with SPR2,and both proteins are required for the splicing of many introns in mitochondria,including nad2 intron 1,2,and 4.These results suggest that a PPR21-(PPR-SMR1/SPR2)-EMP12 complex is involved in the splicing of nad2 introns in maize mitochondria.
基金supported by the National Natural Science Foundation of China(Grant Nos.32272191 and 32350410428).
文摘Male gametes are produced in the anthers and are essential for fertilization and seed setting.A transverse section of the anther reveals four layers:the epidermis,endothecium,middle layer,and tapetum.The tapetum,being the innermost layer,plays a critical role in supplying nutrients,enzymes,and protection to microspores.Detailed microscopic and ultrastructural analyses have revealed highly active and well-organized structures within the tapetum,referred to as tapetal organelles.Molecular studies have highlighted the significance of tapetal cell death and the nurturing role of the tapetum for microspores.However,the mechanisms by which these processes are mediated by tapetal organelles at the cellular level remain elusive.The discovery of mutants defective in tapetal organelles has enabled further investigations into their structure,morphology,and function.This review discusses the molecular and functional roles of various tapetal organelles,such as plastids(amyloplasts and elaioplasts),mitochondria,tapetosomes,endoplasmic reticulum,and lipid bodies.We provide an overview of their roles,highlight key organelles in the tapetum,and address recent challenges and potential applications of genes regulating tapetal organelles in enhancing crop fertility.
