Melatonin Mitigates Atrazine-Induced Renal Tubular Epithelial Cell Senescence by Promoting Parkin-Mediated Mitophagy  

作　　者：Yu-Sheng Shi Tian-Ning Yang Yu-Xiang Wang Xiang-Yu Ma Shuo Liu Yi Zhao Jin-Long Li 

机构地区：[1]College of Veterinary Medicine,Northeast Agricultural University,Harbin 150030,P.R.China [2]Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment,Northeast Agricultural University,Harbin 150030,P.R.China [3]Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine,Northeast Agricultural University,Harbin 150030,P.R.China

出　　处：《Research》2025年第1期135-148,共14页研究(英文)

基　　金：supported by the National Natural Science Foundation of China(no.32172932);Key Program of Natural Science Foundation of Heilongjiang Province of China(no.ZD2021C003);China Agriculture Research System of MOF and MARA(no.CARS-35);Distinguished Professor of Longjiang Scholars Support Project(no.T201908),Heilongjiang Touyan Innovation Team Program.

摘　　要：The accumulation of senescent cells in kidneys is considered to contribute to age-related diseases and organismal aging.Mitochondria are considered a regulator of cell senescence process.Atrazine as a triazine herbicide poses a threat to renal health by disrupting mitochondrial homeostasis.Melatonin plays a critical role in maintaining mitochondrial homeostasis.The present study aims to explore the mechanism by which melatonin alleviates atrazine-induced renal injury and whether parkin-mediated mitophagy contributes to mitigating cell senescence.The study found that the level of parkin was decreased after atrazine exposure and negatively correlated with senescent markers.Melatonin treatment increased serum melatonin levels and mitigates atrazine-induced renal tubular epithelial cell senescence.Mechanistically,melatonin maintains the integrity of mitochondrial crista structure by increasing the levels of mitochondrial contact site and cristae organizing system,mitochondrial transcription factor A(TFAM),adenosine triphosphatase family AAA domain-containing protein 3A(ATAD3A),and sorting and assembly machinery 50(Sam50)to prevent mitochondrial DNA release and subsequent activation of cyclic guanosine 5'-monophosphate-adenosine 5'-monophosphate synthase pathway.Furthermore,melatonin activates Sirtuin 3-superoxide dismutase 2 axis to eliminate the accumulation of reactive oxygen species in the kidney.More importantly,the antisenescence role of melatonin is largely determined by the activation of parkin-dependent mitophagy.These results offer novel insights into measures against cell senescence.Parkin-mediated mitophagy is a promising drug target for alleviating renal tubular epithelial cell senescence.

关 键 词：mitochondrial homeostasis cell senescence processatrazine triazine herbicide parkin mediated mitophagy senescent cells ATRAZINE renal tubular epithelial cell senescence MELATONIN 

分 类 号：R285[医药卫生—中药学] R692[医药卫生—中医学]