title: Involvement of PPARγ in emodin-induced HK-2 cell apoptosis.
abstract: Emodin, a major compound in total rhubarb anthraquinones (TRAs), has exhibited nephrotoxicity in Sprague Dawley rats and cytotoxicity to HK-2 cells, a human proximal tubular epithelial cell line, in our previous study. However, the exact molecular mechanisms underlying emodin-induced cytotoxicity remain undefined. In this study, the exposure of HK-2 cells to emodin led to decreased cell viability, caspase 3 cleavage and activation, loss of mitochondrial membrane potential (DWm), and cytochrome c release from mitochondria to cytosol. Meanwhile, the levels of peroxisome proliferator-activated receptor gamma (PPARγ) mRNA and protein expression were elevated. GW9662, an antagonist of PPARγ, dramatically ameliorated the release of cytochrome c, the activation of caspase 3, and the reduction of cell viability induced by emodin. Importantly, emodin at the concentration causing apoptosis enhanced the stability of PPARγ mRNA. Taken together, these findings suggest that PPARγ might mediate, at least in part, emodin-induced HK-2 cell apoptosis via mitochondrial pathway.
authors.affiliation: National Nanjing Center for Drug Screening, China Pharmaceutical University, 24 Tongjia Alley, Nanjing 210038, China.
authors.forename: Cuifen
authors.initials: C
authors.lastname: Wang
authors.forename: Xiaoniu
authors.initials: X
authors.lastname: Dai
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.forename: Hongwei
authors.initials: H
authors.lastname: Yi
authors.forename: Dongrui
authors.initials: D
authors.lastname: Zhou
authors.forename: Chunhui
authors.initials: C
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Ma
authors.forename: Zhenzhou
authors.initials: Z
authors.lastname: Jiang
authors.forename: Luyong
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000813:Anilides / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004642:Emodin / Q000633:toxicity*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D047495:PPAR gamma; D053148:Caspase 3; D004642:Emodin