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
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
In this editorial,we discuss an article by Wang et al,focusing on the role of mitochondria in peripheral insulin resistance and insulin secretion.Despite numerous in vitro and pre-clinical studies supporting the invol...In this editorial,we discuss an article by Wang et al,focusing on the role of mitochondria in peripheral insulin resistance and insulin secretion.Despite numerous in vitro and pre-clinical studies supporting the involvement of mitochondrial dysfunction and oxidative stress in the pathogenesis of diabetes and its complications,efforts to target mitochondria for glycemic control in diabetes using mitochondria-targeted antioxidants have produced inconsistent results.The intricate functionality of mitochondria is summarized to underscore the challenges it poses as a therapeutic target.While mitochondria-targeted antioxidants have demonstrated improvement in mitochondrial function and oxidative stress in pre-clinical diabetes models,the results regarding glycemic control have been mixed,and no studies have evaluated their hypoglycemic effects in diabetic patients.Nonetheless,pre-clinical trials have shown promising outcomes in ameliorating diabetes-related complications.Here,we review some reasons why mitochondria-targeted antioxidants may not function effectively in the context of mitochondrial dysfunction.We also highlight several alternative approaches under development that may enhance the targeting of mitochondria for diabetes treatment.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
哮喘(bronchial asthma)以气道炎症和高反应性为主要特征,严重危害人类健康^([1])。AMP-activated protein kinase(AMPK)作为氧化还原蛋白,能有效调节细胞内氧化应激,可通过激活高度保守的NAD+依赖性去乙酰化酶Sirtuin 1(SIRT1)/NF-κB...哮喘(bronchial asthma)以气道炎症和高反应性为主要特征,严重危害人类健康^([1])。AMP-activated protein kinase(AMPK)作为氧化还原蛋白,能有效调节细胞内氧化应激,可通过激活高度保守的NAD+依赖性去乙酰化酶Sirtuin 1(SIRT1)/NF-κB通路抑制哮喘^([2])。PPARγcoactivator-1α(PGC-1α)在线粒体生物合成和功能调节中得到广泛应用^([3])。人参皂苷Rb1是人参根茎的重要提取物,具有抗炎,抗凋亡,能够抑制哮喘气道高反应性等作用^([4])。本研究探讨了Rb1可能通过激活AMPK/SIRT1/PGC-1α信号轴改善小鼠支气管上皮细胞在CRE诱导下发生的氧化应激线粒体动力学障碍,最终有效缓解哮喘气道炎症的发生和发展。展开更多
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 .
文摘目的:观察白藜芦醇对多囊卵巢综合征(polycystic ovary syndrome,PCOS)模型大鼠卵巢颗粒细胞增殖和凋亡的影响以及线粒体的形态和功能的改变,并探讨其可能的保护机制。方法:32只雌性SD大鼠幼鼠随机分为2组,PCOS模型组(n=24)和模型对照组(n=8)。成功提取PCOS组颗粒细胞并体外培养,然后用不同浓度的白藜芦醇处理颗粒细胞,CCK-8法检测细胞活力的变化;Mito Tracker Deep Red染色观察细胞线粒体的形态变化;JC-1检测线粒体膜电位的变化;ATP检测试剂盒检测ATP的变化;分光光度计检测与凋亡密切相关casppase-3和caspase-9酶活性变化;最后,蛋白免疫印迹法检测颗粒细胞内caspase-3和caspase-9蛋白水平的变化。结果:白藜芦醇处理PCOS模型大鼠卵巢颗粒细胞后,颗粒细胞的增殖活性明显增强(P=0.000);Mito Tracker Deep Read染色结果显示线粒体质量明显增加,形状呈管状或长条状;颗粒细胞内ATP产量和线粒体膜电位也明显增加(P=0.000、P=0.000)。另外,白藜芦醇也降低了caspase-3和caspase-9酶活性和蛋白水平的表达(P=0.000、P=0.000)。结论:白藜芦醇抑制了PCOS模型大鼠卵巢颗粒细胞的凋亡,也促进了细胞的增殖,其机制与白藜芦醇改善颗粒细胞线粒体的形态和功能有关。
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 Instituto de Ciencia,Tecnología e Innovación-Gobierno del Estado de Michoacán,México,No.ICTI-PICIR23-063Programa Proyectos de Investigación Financiados 2024,Coordinación de Investigación Científica,Universidad Michoacana de San Nicolás de Hidalgo,México.
文摘In this editorial,we discuss an article by Wang et al,focusing on the role of mitochondria in peripheral insulin resistance and insulin secretion.Despite numerous in vitro and pre-clinical studies supporting the involvement of mitochondrial dysfunction and oxidative stress in the pathogenesis of diabetes and its complications,efforts to target mitochondria for glycemic control in diabetes using mitochondria-targeted antioxidants have produced inconsistent results.The intricate functionality of mitochondria is summarized to underscore the challenges it poses as a therapeutic target.While mitochondria-targeted antioxidants have demonstrated improvement in mitochondrial function and oxidative stress in pre-clinical diabetes models,the results regarding glycemic control have been mixed,and no studies have evaluated their hypoglycemic effects in diabetic patients.Nonetheless,pre-clinical trials have shown promising outcomes in ameliorating diabetes-related complications.Here,we review some reasons why mitochondria-targeted antioxidants may not function effectively in the context of mitochondrial dysfunction.We also highlight several alternative approaches under development that may enhance the targeting of mitochondria for diabetes treatment.
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.
文摘哮喘(bronchial asthma)以气道炎症和高反应性为主要特征,严重危害人类健康^([1])。AMP-activated protein kinase(AMPK)作为氧化还原蛋白,能有效调节细胞内氧化应激,可通过激活高度保守的NAD+依赖性去乙酰化酶Sirtuin 1(SIRT1)/NF-κB通路抑制哮喘^([2])。PPARγcoactivator-1α(PGC-1α)在线粒体生物合成和功能调节中得到广泛应用^([3])。人参皂苷Rb1是人参根茎的重要提取物,具有抗炎,抗凋亡,能够抑制哮喘气道高反应性等作用^([4])。本研究探讨了Rb1可能通过激活AMPK/SIRT1/PGC-1α信号轴改善小鼠支气管上皮细胞在CRE诱导下发生的氧化应激线粒体动力学障碍,最终有效缓解哮喘气道炎症的发生和发展。
