Aerobic exercise alleviates oxidative stress-induced apoptosis in kidneys of myocardial infarction mice by inhibiting ALCAT1 and activating FNDC5/Irisin signaling pathway
Aerobic exercise alleviates oxidative stress-induced apoptosis in kidneys of myocardial infarction mice by inhibiting ALCAT1 and activating FNDC5/Irisin signaling pathway
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有氧运动通过抑制ALCAT1、激活FNDC5/Irisin信号通路减轻氧化应激诱导的心肌梗死小鼠肾脏细胞凋亡
DOI：
10.1016/j.freeradbiomed.2020.06.038
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发表时间：
2020-10-01
影响因子：
7.4
通讯作者：
Tian, Zhenjun
中科院分区：
文献类型：
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作者：
Wu, Fangnan;Li, Zhuo;Tian, Zhenjun
有氧运动有助于改善肾损伤，但其潜在机制尚未完全阐明。在本研究中，我们阐释了有氧运动改善心肌梗死（MI）后肾损伤的潜在机制。在体内实验中，使用野生型和alcat1基因敲除小鼠建立心肌梗死模型，并使其进行为期六周的中等强度有氧运动。在体外实验中，采用经过氧化氢（H₂O₂）和重组人鸢尾素（rhIrisin）处理的正常大鼠肾（NRK）细胞来探究潜在机制。我们的研究结果显示，有氧运动可使心肌梗死后肾脏中的鸢尾素表达上调，而ALCAT1表达降低。在alcat1基因敲除小鼠中，我们发现ALCAT1参与了心肌梗死小鼠受损肾脏组织中氧化应激和细胞凋亡的进程，然而有氧运动逆转了这些变化。此外，在体外实验中我们观察到，鸢尾素可部分通过AMPK - Sirt1 - PGC - 1α通路，抑制H₂O₂处理或alcat1过表达诱导的NRK细胞氧化应激和细胞凋亡。这些研究结果表明，有氧运动部分通过激活FNDC5 /鸢尾素 - AMPK - Sirt1 - PGC - 1α信号通路并抑制ALCAT1表达，参与减轻心肌梗死后受损肾脏组织中的氧化应激和细胞凋亡水平。
Aerobic exercise involves in ameliorating kidney injury, but the underlying mechanisms are not fully clarified. In this study, we elucidated the potential mechanisms of aerobic exercise in ameliorating kidney injury following myocardial infarction (MI). In vivo, wildtype and alcat1 knockout mice were used to establish the MI model, and subjected to six-week moderate-intensity aerobic exercise. In vitro, Normal Rat Kidney (NRK) cells treated with H2O2 and recombinant human Irisin (rhIrisin) were used for exploring potential mechanisms. Our results showed that Irisin expression was up-regulated by aerobic exercise in kidneys after MI, while ALCAT1 was reduced. In alcat1 knockout mice, we found that ALCAT1 involved in the progressions of oxidative stress and apoptosis in impaired kidney tissues of MI mice, but aerobic exercise reversed these changes. Furthermore, in vitro, we observed that Irisin inhibited both H2O2-treatment or overexpression of alcat1-induced oxidative stress and apoptosis in NRK cells, partially via AMPK-Sirt1-PGC-1 alpha pathway. These findings reveal that aerobic exercise participates in Yalleviating the levels of oxidative stress and apoptosis in impaired kidney tissues following MI, partially via activating FNDC5/Irisin-AMPK-Sirt1-PGC-1 alpha signaling pathway and inhibiting ALCAT1 expression.