title: A Ca2+chelator ameliorates chromium (VI)-induced hepatocyte L-02 injury via down-regulation of voltage-Dependent anion channel 1 (VDAC1) expression.
abstract: Hexavalent chromium could result in cell malfunctions. Intracellular Ca2+([Ca2+]i) content and VDAC1 expression are both important features related to cell survial. This study aimed to explore the mechanism of cell injury induced by Cr(VI) and tentatively offer clues to repairing this cell damage using [Ca2+]iand VDAC1. L-02 hepatocytes were treated with Cr(VI)/BAPTA, and the levels of [Ca2+]iand cell injury associated with Cr(VI) were determined in addition to the effect of BAPTA. The expression of VDAC1 in Cr(VI)-induced cells was evaluated. The results showed a dose-dependent elevation of the level of VDAC1 and the mRNA level of the VDAC1 biogenesis-related gene Sam50. BAPTA could ameliorate less severe damage induced by 4μM Cr(VI) via reducing VDAC1 and Sam50. Additionally, cell injury caused by less than 4μM Cr(VI) could be ameliorated by VDAC1 knockdown. Taken together, the findings of this study suggest that inhibition of intracellular Ca2±overload could protect cells from damage and that VDAC1 plays a considerable role in Cr(VI)-induced liver injury.
authors.affiliation: Department of Health Toxicology, School of Public Health, Central South University, Changsha 410078, PR China.
authors.forename: Xing
authors.initials: X
authors.lastname: Yi
authors.affiliation: Department of Health Toxicology, School of Public Health, Central South University, Changsha 410078, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Department of Health Toxicology, School of Public Health, Central South University, Changsha 410078, PR China.
authors.forename: Xiali
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Hunan Provincial Centers for Disease Control and Prevention, Changsha 410005, PR China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Duan
authors.affiliation: Department of Health Toxicology, School of Public Health, Central South University, Changsha 410078, PR China.
authors.forename: Kaihua
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Health Toxicology, School of Public Health, Central South University, Changsha 410078, PR China. Electronic address: caigaozhong@gmail.com.
authors.forename: Caigao
authors.initials: C
authors.lastname: Zhong
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002614:Chelating Agents / Q000494:pharmacology; D002857:Chromium / Q000633:toxicity*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics; D050995:Voltage-Dependent Anion Channel 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D002614:Chelating Agents; D034741:RNA, Small Interfering; C494762:VDAC1 protein, human; D002857:Chromium; C074702:chromium hexavalent ion; D004533:Egtazic Acid; D050995:Voltage-Dependent Anion Channel 1; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium
keywords: 1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid tetrakis(acetoxymethyl ester) (BAPTA-AM); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST); Hexavalent chromium [Cr(VI)]; Intracellular calcium content ([Ca(2+)](i)); L-02 hepatocytes; Voltage-dependent anion channel 1 (VDAC1)