氧化应激
药理学
活性氧
缺血
缺氧(环境)
肉碱
急性肾损伤
过氧化物酶体
线粒体
体内
再灌注损伤
肾
肾缺血
细胞凋亡
化学
医学
受体
生物
内分泌学
生物化学
内科学
氧气
生物技术
有机化学
作者
Zhiyu Wang,Zongjie Fu,Chongjian Wang,Jing Xu,Hongkun Ma,Mengdi Jiang,Tingting Xu,Xiaobei Feng,Wen Zhang
摘要
To date, the treatment of acute kidney injury (AKI) remains a difficult problem for clinicians. In the present study, we assessed whether ZLN005, a novel peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) agonist, can protect against ischemic AKI in vivo and in vitro. Notably, ZLN005 treatment significantly alleviated Ischemia-reperfusion (I/R)-induced tubular injury and reversed the decrease in hypoxia-reoxygenation-induced cell viability by restoring PGC-1α expression in a dose-dependent manner. This beneficial effect of ZLN005 was associated with the preservation of mitochondrial fatty acid oxidation (MitoFAO) and the alleviation of oxidative stress. Cotreatment with etomoxir, a specific inhibitor of carnitine palmitoyltransferase-1α (CPT-1α) activity, or CPT-1α siRNA abrogated ZLN005-induced antistress responses by mitigating reactive oxygen species production and decreasing apoptosis under ischemia-hypoxia conditions by suppressing MitoFAO. Further studies revealed that activation of endoplasmic reticulum (ER) stress may be involved in the effect of CPT-1α inhibition observed in vivo and in vitro. Collectively, our results suggest that ZLN005 confers a protective effect on I/R-induced kidney injury by mitigating ER stress through the restoration of MitoFAO by targeting PGC-1α.
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