title: Overexpressed cyclophilin B suppresses aldosterone-induced proximal tubular cell injury both in vitro and in vivo.
abstract: The renin-angiotensin-aldosterone system (RAAS) is overactivated in patients with chronic kidney disease. Oxidative stress and endoplasmic reticulum stress (ERS) are two major mechanisms responsible for aldosterone-induced kidney injury. Cyclophilin (CYP) B is a chaperone protein that accelerates the rate of protein folding through its peptidyl-prolyl cis-trans isomerase (PPIase) activity. We report that overexpression of wild-type CYPB attenuated aldosterone-induced oxidative stress (evidenced by reduced production of reactive oxygen species and improved mitochondrial dysfunction), ERS (indicated by reduced expression of the ERS markers glucose-regulated protein 78 [GRP78] and C/-EBP homologous protein [CHOP]), and tubular cell apoptosis in comparison with aldosterone-induced human kidney-2 (HK-2) cells. The in vivo study also yielded similar results. Hence, CYPB performs a crucial function in protecting cells against aldosterone-induced oxidative stress, ERS, and tubular cell injury via its PPIase activity.
authors.affiliation: Division of Nephrology, Huashan Hospital and Institute of Nephrology, Fudan University, Xuhui, Shanghai, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Division of Nephrology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, P.R. China.
authors.forename: Lilu
authors.initials: L
authors.lastname: Lin
authors.affiliation: College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, P.R. China.
authors.forename: Haidong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Division of Nephrology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, P.R. China.
authors.forename: Honglei
authors.initials: H
authors.lastname: Guo
authors.affiliation: Division of Nephrology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Division of Nephrology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ding
mesh_terms: D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D021983:Cyclophilins / Q000235:genetics / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000187:drug effects*; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000378:metabolism
chemical_list: C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D017382:Reactive Oxygen Species; C081786:cyclophilin B; D051742:Transcription Factor CHOP; D000450:Aldosterone; D021983:Cyclophilins
keywords: Pathology Section; aldosterone; apoptosis; endoplasmic reticulum stress; oxidative stress; tubular cell