This paper focuses on a bioenergetic mechanism responding to hypoxia. This response involves hypoxia-induced reprogramming of respiratory chain function and switching from oxidation of complex I (NAD-related substrate...This paper focuses on a bioenergetic mechanism responding to hypoxia. This response involves hypoxia-induced reprogramming of respiratory chain function and switching from oxidation of complex I (NAD-related substrates) to complex II (succinate oxidation). Transient, reversible, compensatory activation of respiratory chain complex II is a major mechanism of urgent adaptation to hypoxia, which is necessary for 1) succinate-related energy synthesis in the conditions of oxygen shortage and formation of urgent resistance;2) succinate-related stabilization of HIF-1α and initiation of its transcriptional activity related with formation of long-term adaptation;3) succinate-dependent activation of the succinate-specific receptor GPR91. Thus, mitochondria perform a signaling function with succinate as a signaling molecule. Effects of succinate in hypoxia occur at three levels, intramitochondrial, intracellular and intercellular. In these settings, succinate displays antihypoxic activity. The review is focused on tactics and strategy for development of the antihypoxic defense and antihypoxants with energotropic properties.展开更多
目的研究压力对视网膜星形胶质细胞(RA)的损伤作用及可能的线粒体机制,为进一步阐明青光眼视神经损害的复杂分子机制提供实验数据。方法对体外培养的RA施加30 mm Hg(1 mm Hg=0.133kP a)压力,模拟慢性高眼压。分别在加压后不同时间点观...目的研究压力对视网膜星形胶质细胞(RA)的损伤作用及可能的线粒体机制,为进一步阐明青光眼视神经损害的复杂分子机制提供实验数据。方法对体外培养的RA施加30 mm Hg(1 mm Hg=0.133kP a)压力,模拟慢性高眼压。分别在加压后不同时间点观察细胞线粒体形态及活性氧(ROS)含量变化,并收集细胞,制备细胞匀浆,采用生物化学方法检测5个线粒体呼吸链复合物(MRCC)和总超氧化物歧化酶(SOD)、Cu/Zn-SOD及Mn-SOD的活性变化。结果压力作用后,RA线粒体的分裂及ROS含量均增加;MRCCⅠ、Ⅱ、Ⅲ、Ⅳ的活性下降,MRCCⅤ的活性随加压时间的延长逐渐升高;各型SOD活性均降低,但Mn-SOD活性下降最迅速、幅度最大。结论压力可以引起RA线粒体形态和功能异常,导致RA内活性氧增加及抗氧化能力下降等损伤性变化。展开更多
文摘This paper focuses on a bioenergetic mechanism responding to hypoxia. This response involves hypoxia-induced reprogramming of respiratory chain function and switching from oxidation of complex I (NAD-related substrates) to complex II (succinate oxidation). Transient, reversible, compensatory activation of respiratory chain complex II is a major mechanism of urgent adaptation to hypoxia, which is necessary for 1) succinate-related energy synthesis in the conditions of oxygen shortage and formation of urgent resistance;2) succinate-related stabilization of HIF-1α and initiation of its transcriptional activity related with formation of long-term adaptation;3) succinate-dependent activation of the succinate-specific receptor GPR91. Thus, mitochondria perform a signaling function with succinate as a signaling molecule. Effects of succinate in hypoxia occur at three levels, intramitochondrial, intracellular and intercellular. In these settings, succinate displays antihypoxic activity. The review is focused on tactics and strategy for development of the antihypoxic defense and antihypoxants with energotropic properties.
文摘目的研究压力对视网膜星形胶质细胞(RA)的损伤作用及可能的线粒体机制,为进一步阐明青光眼视神经损害的复杂分子机制提供实验数据。方法对体外培养的RA施加30 mm Hg(1 mm Hg=0.133kP a)压力,模拟慢性高眼压。分别在加压后不同时间点观察细胞线粒体形态及活性氧(ROS)含量变化,并收集细胞,制备细胞匀浆,采用生物化学方法检测5个线粒体呼吸链复合物(MRCC)和总超氧化物歧化酶(SOD)、Cu/Zn-SOD及Mn-SOD的活性变化。结果压力作用后,RA线粒体的分裂及ROS含量均增加;MRCCⅠ、Ⅱ、Ⅲ、Ⅳ的活性下降,MRCCⅤ的活性随加压时间的延长逐渐升高;各型SOD活性均降低,但Mn-SOD活性下降最迅速、幅度最大。结论压力可以引起RA线粒体形态和功能异常,导致RA内活性氧增加及抗氧化能力下降等损伤性变化。
