Keywords: 
• Cr(Ⅵ) /
• VDAC /
• MPTP /
• apoptosis

Abstract: Chromium is a widely used chemical, which demonstrated the acute and chronic toxicity, including neurotoxicity, genotoxicity, carcinogenicity and immunotoxicity. We aimed to provide experimental evidence for the prevention and cure of the hexavalent chromium (Cr(Ⅵ))-induced hazard. Voltage-dependent anion channel-1 (VDAC1) is an essential player in mammalian apoptosis by regulating mitochondrial membrane permeability. VDAC1 is a key functional target of the BCL-2 protein family, and BAX and BAK can interact with VDAC1 and form a large pore, through which apoptogenic proteins such as cytochrome C released. But the molecular mechanism of VDAC1 in cell apoptosis is still not clear. We established the VDAC1 stably knocked-down cell lines L02-VDAC1-1 and shVDAC1-2 through sustained expression of shRNA against VDAC1 and then detected the survival rate, the apoptosis rate, reactive oxygen species (ROS) production, mitochondrial function and the contents of apoptosis inducing factor. The result showed that the survival rate of the shVDAC is higher than that of L02 and the apoptosis rate is decreased. The result concerning ROS production showed that knocking down of VDAC1 can prevent Cr(Ⅵ)-induced ROS accumulation compared with L02. The inner MPTP and the contents of cytochrome C (cyt C) and apoptosis inducing factors were significantly increased in response to Cr(Ⅵ) stimuli in L02, but these phenomena did not occur in shVDAC1. The results in this study demonstrated that VDAC1 mediates Cr(Ⅵ)-induced L02 hepatocytes apoptosis, and the inhibition of VDAC1 expression could reduce the adverse effects induced by Cr(Ⅵ) exposure.