title: Proteomic identification of mitochondrial targets involved in andrographolide sodium bisulfite-induced nephrotoxicity in a rat model.
abstract: Our previous works have indicated that the mitochondrion is the primary target of nephrotoxicity induced by andrographolide sodium bisulfate (ASB), but the mechanisms of ASB-induced nephrotoxicity have remained largely unknown. In this study, proteomic analysis was used to explore the changes in the renal mitochondrial proteome in SD rats after treatment with ASB. SD rats were intraperitoneally administered with ASB (100, 600mg/kg/d) for 7 days. Renal impairment was evaluated by pathological observation. Two-dimensional gel electrophoresis (2-DE), as well as matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS), was applied for the identification of mitochondrial protein and was validated by Western blotting. Protein-protein interactions were analyzed using a Web-based bioinformatics tool (STRING, version 9.1). Rat kidneys exhibited histopathological changes after treatment with ASB, and 13 proteins were significantly changed, including ES1 protein homolog, heat shock cognate 71kDa protein, peroxiredoxin-1 (Prdx1), cytochrome C oxidase subunit 5B (COX5B), prohibitin (PHB), threonine-tRNA ligase, pyruvate dehydrogenase E1 component subunit beta (PDH-β), voltage-dependent anion-selective channel protein 2 (VDAC2), voltage-dependent anion-selective channel protein 1 (VDAC1), adenylate kinase 2 (KAD2) and others. These data demonstrated that the expression levels of several proteins significantly changed in the mitochondria, and these proteins could be candidate biomarkers for ASB-induced nephrotoxicity.
authors.affiliation: School of Pharmacology, Zhejiang Chinese Medical University, Hangzhou, PR China.
authors.forename: Wen Min
authors.initials: WM
authors.lastname: Xing
authors.affiliation: School of Pharmacology, Zhejiang Chinese Medical University, Hangzhou, PR China.
authors.forename: Tang Juan
authors.initials: TJ
authors.lastname: Yuan
authors.affiliation: School of Pharmacology, Zhejiang Chinese Medical University, Hangzhou, PR China.
authors.forename: Jia Dong
authors.initials: JD
authors.lastname: Xu
authors.affiliation: School of Pharmacology, Zhejiang Chinese Medical University, Hangzhou, PR China.
authors.forename: Li Li
authors.initials: LL
authors.lastname: Gu
authors.affiliation: School of Pharmacology, Zhejiang Chinese Medical University, Hangzhou, PR China.
authors.forename: Pei
authors.initials: P
authors.lastname: Liang
authors.affiliation: School of Pharmacology, Zhejiang Chinese Medical University, Hangzhou, PR China. Electronic address: luhong@hotmail.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007274:Injections, Intraperitoneal; D024101:Mitochondrial Proteins / Q000187:drug effects / Q000378:metabolism*; D000091402:Prohibitins; D040901:Proteomics / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013447:Sulfites / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D024101:Mitochondrial Proteins; C000717332:Phb protein, rat; D000091402:Prohibitins; D013447:Sulfites; C009279:sodium bisulfite
keywords: Andrographolide sodium bisulfate; Mitochondrion; Nephrotoxicity; Proteomics