Augmenter of liver regeneration promotes mitochondrial biogenesis in renal ischemia-reperfusion injury
Augmenter of liver regeneration promotes mitochondrial biogenesis in renal ischemia-reperfusion injury
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DOI：
10.1007/s10495-018-1487-2
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发表时间：
2018-12-01
期刊：
影响因子：
7.2
通讯作者：
Liao, Xiao-hui
中科院分区：
文献类型：
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作者：
Huang, Li-li;Long, Rui-ting;Liao, Xiao-hui
线粒体是细胞能量代谢的中心，也是各种毒物和缺血性损伤的优先靶点。肾缺血再灌注 (I/R) 损伤会引发近端肾小管损伤，线粒体被认为是 I/R 损伤的主要亚细胞靶标。促进线粒体生物发生（MB）对于预防 I/R 损伤至关重要。我们前期的研究结果表明，肝再生增强剂（ALR）具有抗凋亡和抗氧化功能。然而，ALR的调节机制仍不清楚，值得进一步研究。为了进一步了解 ALR 在 MB 中的作用，用携带 ALR 短干扰 RNA (siRNA) 的慢病毒处理人肾 (HK)-2 细胞，并创建体外缺氧复氧 (H/R) 损伤模型。我们观察到，敲低 ALR 会促进肾小管细胞凋亡并加重线粒体损伤，线粒体呼吸蛋白三磷酸腺苷 (ATP) 合酶亚基、细胞色素 C 氧化酶亚基 1 和烟酰胺腺嘌呤二核苷酸脱氢酶（泛醌）β 的减少就证明了这一点。 亚复合物8。同时，与siRNA/对照组相比，HK-2细胞中活性氧的产生增加，ATP水平显着降低（p
Mitochondria are the center of energy metabolism in the cell and the preferential target of various toxicants and ischemic injury. Renal ischemia-reperfusion (I/R) injury triggers proximal tubule injury and the mitochondria are believed to be the primary subcellular target of I/R injury. The promotion of mitochondrial biogenesis (MB) is critical for the prevention I/R injury. The results of our previous study showed that augmenter of liver regeneration (ALR) has anti-apoptotic and anti-oxidant functions. However, the modulatory mechanism of ALR remains unclear and warrants further investigation. To gain further insight into the role of ALR in MB, human kidney (HK)-2 cells were treated with lentiviruses carrying ALR short interfering RNA (siRNA) and a model of hypoxia reoxygenation (H/R) injury in vitro was created. We observed that knockdown of ALR promoted apoptosis of renal tubular cells and aggravated mitochondrial injury, as evidenced by the decrease in the mitochondrial respiratory proteins adenosine triphosphate (ATP) synthase subunit , cytochrome c oxidase subunit 1, and nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) beta subcomplex 8. Meanwhile, the production of reactive oxygen species was increased and ATP levels were decreased significantly in HK-2 cells, as compared with the siRNA/control group (p