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Pysregulation of mitochondrial biogenesis in vascular endothelial and smooth muscle cells of aged rats

机译:老年大鼠血管内皮和平滑肌细胞线粒体生物发生的调理

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Mitochondrial biogenesis is involved in the control of cell metabolism, signal transduction, and regulation of mitochondrial reactive oxygen species (ROS) production. Despite the central role of mitochondria in cellular aging and endothelial physiology, there are no studies extant investigating age-related alterations in mitochondrial biogenesis in blood vessels. Electronmicroscopyand confocal microscopy (en face Mitotracker staining) revealed that in aortas of F344 rats, a decline in mitochondrial biogenesis occurs with aging. In aged vessels, the expression of the mitochondrial biogenesis factors (including mitochondrial transcription factor A and peroxisome proliferator-activated receptor-gamma coactivator-1)was decreased. The vascular expression of complex I, III, and IV significantly declined with age, whereas aging did not alter the expression of complex II and V. Cytochrome c oxidase (COX) expression/activity exhibited the greatest age-related decline, which was associated with increased mitochondrial ROS production in the aged vessels. In cultured coronary arterial endothelial cells, a partial knockdown of COX significantly increased mitochondrial ROS production. In conclusion, vascular aging is characterized by a decline in mitochondrial mass in the endothelial cells and an altered expression of components of the mitochondrial electron transport chain likely due to a dysregulation of mitochondrial biogenesis factors. We posit that impaired mitochondrial biogenesis and downregulation of COX may contribute to the increased mitochondrial oxidative stress in aged endothelial cells.
机译:线粒体生物发生参与细胞代谢的控制,信号转导和线粒体活性氧(ROS)产生的调节。尽管线粒体在细胞衰老和内皮生理中起着核心作用,但目前尚无研究研究与年龄相关的血管线粒体生物发生变化。电镜和共聚焦显微镜(面对Mitotracker染色)显示,在F344大鼠的主动脉中,随着衰老,线粒体生物发生减少。在衰老的血管中,线粒体生物发生因子(包括线粒体转录因子A和过氧化物酶体增殖物激活的受体-γcoactivator-1)的表达下降。随着年龄的增长,复合物I,III和IV的血管表达显着下降,而衰老并没有改变复合物II和V的表达。细胞色素C氧化酶(COX)的表达/活性表现出最大的年龄相关性下降,这与老化血管中线粒体ROS的产生增加。在培养的冠状动脉内皮细胞中,COX的部分敲低显着增加了线粒体ROS的产生。总之,血管衰老的特征在于内皮细胞中线粒体质量的下降以及线粒体电子传输链各成分表达的改变,这可能是由于线粒体生物发生因子的失调所致。我们认为受损的线粒体生物发生和COX的下调可能有助于增加衰老的内皮细胞中线粒体的氧化应激。

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