title: The role of STIM1 in the Cr(vi)-induced [Ca2+]iincrease and cell injury in L-02 hepatocytes.
abstract: Hexavalent chromium [Cr(vi)] is a potent cytotoxin and carcinogen. In recent years, drinking water contamination with Cr(vi) has become a worldwide problem of significant public health importance, thus much attention has been paid to the investigation of Cr(vi)-induced hepatotoxicity. The concentration of intracellular calcium ions ([Ca2+]i) was found to be increased after Cr(vi) exposure, but the exact underlying mechanisms involved in the Ca2+homeostasis imbalance remain poorly characterized. In the present study, by utilizing the antagonist of store-operated calcium channels (SOCCs) 2-aminoethoxydiphenyl borate (2-APB), small interfering RNA against stromal interaction molecule 1 (si-STIM1) and antioxidant N-acetylcysteine (NAC), we found that Cr(vi) induces [Ca2+]iincrease, cell viability loss and transaminase (AST/ALT) leakage, and that these could be suppressed by both 2-APB and si-STIM1. NAC significantly alleviated Cr(vi)-induced up-regulation of STIM1, phosphorylated-extracellular-signal-regulated kinases 1 and 2 (p-ERK1/2), ERK1/2 and nuclear factor κB (NF-κB). By utilizing the ERK inhibitor U0126 and the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC), we confirmed that STIM1 can be regulated by ERK and NF-κB. Thus we concluded that STIM1 plays a role in the Cr(vi)-induced [Ca2+]iincrease and cell injury. Our current data provide new insights into the mechanisms of STIM1 function in Cr(vi)-induced hepatotoxicity, and may provide experimental clues for the prevention and treatment of liver diseases in the occupational population exposed to Cr(vi).
authors.affiliation: Department of Health Toxicology, Xiangya School of Public Health, Central South University, Changsha 410078, P. R. China. fangxiao@csu.edu.cn.
authors.forename: Xing
authors.initials: X
authors.lastname: Yi
authors.affiliation: Department of Health Toxicology, Xiangya School of Public Health, Central South University, Changsha 410078, P. R. China. fangxiao@csu.edu.cn.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Health Toxicology, Xiangya School of Public Health, Central South University, Changsha 410078, P. R. China. fangxiao@csu.edu.cn.
authors.forename: Caigao
authors.initials: C
authors.lastname: Zhong
authors.affiliation: Department of Health Toxicology, Xiangya School of Public Health, Central South University, Changsha 410078, P. R. China. fangxiao@csu.edu.cn.
authors.forename: Xiali
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Department of Health Toxicology, Xiangya School of Public Health, Central South University, Changsha 410078, P. R. China. fangxiao@csu.edu.cn.
authors.forename: Fang
authors.initials: F
authors.lastname: Xiao
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002461:Cell Line, Transformed; D002857:Chromium / Q000633:toxicity*; D055785:Gene Knockdown Techniques; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D000071737:Stromal Interaction Molecule 1 / Q000235:genetics / Q000502:physiology*
chemical_list: D009363:Neoplasm Proteins; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D002857:Chromium; C074702:chromium hexavalent ion; D002118:Calcium; D000111:Acetylcysteine