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Article

Hexavalent chromium targets mitochondrial respiratory chain complex I to induce reactive oxygen species-dependent caspase-3 activation in L-02 hepatocytes

  • Authors:
    • Fang Xiao
    • Yanhong Li
    • Lu Dai
    • Yuanyuan Deng
    • Yue Zou
    • Peng Li
    • Yuan Yang
    • Caigao Zhong
  • View Affiliations / Copyright

    Affiliations: Department of Health Toxicology, School of Public Health, Central South University, Changsha 410078, P.R. China
  • Pages: 629-635
    |
    Published online on: June 14, 2012
       https://doi.org/10.3892/ijmm.2012.1031
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Abstract

Hexavalent chromium [Cr(VI)], which is used for various industrial applications, such as leather tanning and chroming, can cause a number of human diseases including inflammation and cancer. Cr(VI) exposure leads to severe damage to the liver, but the mechanisms involved in Cr(VI)-mediated toxicity in the liver are unclear. The present study provides evidence that Cr(VI) enhances reactive oxygen species (ROS) accumulation by inhibiting the mitochondrial respiratory chain complex (MRCC) I. Cr(VI) did not affect the expression levels of antioxidative proteins such as superoxide dismutase (SOD), catalase and thioredoxin (Trx), indicating that the antioxidative system was not involved in Cr(VI)-induced ROS accumulation. We found that ROS mediated caspase-3 activation partially depends on the downregulation of the heat shock protein (HSP) 70 and 90. In order to confirm our hypothesis that ROS plays a key role in Cr(VI)-mediated cytotoxicity, we used N-acetylcysteine (NAC) to inhibit the accumulation of ROS. NAC successfully blocked the inhibition of HSP70 and HSP90 as well as the activation of caspase-3, suggesting that ROS is essential in Cr(VI)-induced caspase-3 activation. By applying different MRCC substrates as electron donors, we also confirmed that Cr(VI) could accept the electrons leaked from MRCC I and the reduction occurs at MRCC I. In conclusion, the present study demonstrates that Cr(VI) induces ROS-dependent caspase-3 activation by inhibiting MRCC I activity, and MRCC I has been identified as a new target and a new mechanism for the apoptosis-inducing activity displayed by Cr(VI).
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Copy and paste a formatted citation
Spandidos Publications style
Xiao F, Li Y, Dai L, Deng Y, Zou Y, Li P, Yang Y and Zhong C: Hexavalent chromium targets mitochondrial respiratory chain complex I to induce reactive oxygen species-dependent caspase-3 activation in L-02 hepatocytes. Int J Mol Med 30: 629-635, 2012.
APA
Xiao, F., Li, Y., Dai, L., Deng, Y., Zou, Y., Li, P. ... Zhong, C. (2012). Hexavalent chromium targets mitochondrial respiratory chain complex I to induce reactive oxygen species-dependent caspase-3 activation in L-02 hepatocytes. International Journal of Molecular Medicine, 30, 629-635. https://doi.org/10.3892/ijmm.2012.1031
MLA
Xiao, F., Li, Y., Dai, L., Deng, Y., Zou, Y., Li, P., Yang, Y., Zhong, C."Hexavalent chromium targets mitochondrial respiratory chain complex I to induce reactive oxygen species-dependent caspase-3 activation in L-02 hepatocytes". International Journal of Molecular Medicine 30.3 (2012): 629-635.
Chicago
Xiao, F., Li, Y., Dai, L., Deng, Y., Zou, Y., Li, P., Yang, Y., Zhong, C."Hexavalent chromium targets mitochondrial respiratory chain complex I to induce reactive oxygen species-dependent caspase-3 activation in L-02 hepatocytes". International Journal of Molecular Medicine 30, no. 3 (2012): 629-635. https://doi.org/10.3892/ijmm.2012.1031
Copy and paste a formatted citation
x
Spandidos Publications style
Xiao F, Li Y, Dai L, Deng Y, Zou Y, Li P, Yang Y and Zhong C: Hexavalent chromium targets mitochondrial respiratory chain complex I to induce reactive oxygen species-dependent caspase-3 activation in L-02 hepatocytes. Int J Mol Med 30: 629-635, 2012.
APA
Xiao, F., Li, Y., Dai, L., Deng, Y., Zou, Y., Li, P. ... Zhong, C. (2012). Hexavalent chromium targets mitochondrial respiratory chain complex I to induce reactive oxygen species-dependent caspase-3 activation in L-02 hepatocytes. International Journal of Molecular Medicine, 30, 629-635. https://doi.org/10.3892/ijmm.2012.1031
MLA
Xiao, F., Li, Y., Dai, L., Deng, Y., Zou, Y., Li, P., Yang, Y., Zhong, C."Hexavalent chromium targets mitochondrial respiratory chain complex I to induce reactive oxygen species-dependent caspase-3 activation in L-02 hepatocytes". International Journal of Molecular Medicine 30.3 (2012): 629-635.
Chicago
Xiao, F., Li, Y., Dai, L., Deng, Y., Zou, Y., Li, P., Yang, Y., Zhong, C."Hexavalent chromium targets mitochondrial respiratory chain complex I to induce reactive oxygen species-dependent caspase-3 activation in L-02 hepatocytes". International Journal of Molecular Medicine 30, no. 3 (2012): 629-635. https://doi.org/10.3892/ijmm.2012.1031
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