TFAM公司
SIRT3
褪黑素
急性肾损伤
锡尔图因
生物
线粒体
肾
内科学
药理学
败血症
内分泌学
线粒体生物发生
免疫学
医学
细胞生物学
乙酰化
生物化学
基因
作者
Zhenmiao Deng,Man He,Hongbin Hu,Wenqian Zhang,Yaoyuan Zhang,Yizhi Ge,Tran Ma,Jie Wu,Lulan Li,Maomao Sun,Sheng An,Jiaxin Li,Qiaobing Huang,Shenhai Gong,Jiaxing Zhang,Zhongqing Chen,Zhenhua Zeng
出处
期刊:Autophagy
[Informa]
日期:2023-08-31
卷期号:20 (1): 151-165
被引量:5
标识
DOI:10.1080/15548627.2023.2252265
摘要
A growing number of studies have shown that melatonin is a potent agonist of SIRT3 (sirtuin 3) and effectively protects mitochondria, suggesting melatonin as a promising therapeutic drug to treat sepsis-induced acute kidney injury (SAKI). In this study, we first included 48 sepsis patients for cross-sectional analysis and the result revealed that plasma melatonin levels are inversely proportional to the mitochondrial injury of renal tubular epithelial cells and directly proportional to the acute kidney injury recovery in sepsis patients. We further explored the effects of exogenous melatonin on SAKI and its mechanism in animal model of cecal ligation and puncture-treated mice, and cellular model of LPS-challenged HK-2 cells. The results demonstrate that the protective effect of melatonin on the progression of SAKI depends on SIRT3 activation as well as mitophagic flux. Mechanistically, TFAM (transcription factor A, mitochondrial)-K154 site deacetylation via SIRT3 is indispensable for melatonin-enhanced mitophagic flux on SAKI. Together, our study unveils a previously unappreciated mechanism of melatonin as agonists of SIRT3 to hold promise for treatment of patients with SAKI.Abbreviations AKI: acute kidney injury; ATP: adenosine triphosphate; BUN: blood urea nitrogen; CLP: cecal ligation and puncture; eGFR: estimated glomerular filtration rate; H&E: hematoxylin and eosin staining; LCN2/NGAL: lipocalin 2; LPS: lipopolysaccharide; LTL: lotus tetragonolobus lectin; mKeima: mitochondria-targeted Keima; mtDNA: mitochondrial DNA; PAS: periodic acid – Schiff staining; RTECs: renal tubular epithelial cells; SAKI: sepsis-induced acute kidney injury; Scr: serum creatinine; SIRT3: sirtuin 3; TFAM: transcription factor A, mitochondrial; TMRE: tetramethylrhodamine.
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