Role of mitochondrial damage in Cr(VI)‑induced endoplasmic reticulum stress in L‑02 hepatocytes

Liang,Qi; Zhang,Yujing; Huang,Manfeng; Xiao,Yuanyuan; Xiao,Fang

doi:10.3892/mmr.2018.9704

Role of mitochondrial damage in Cr(VI)‑induced endoplasmic reticulum stress in L‑02 hepatocytes

Authors:
- Qi Liang
- Yujing Zhang
- Manfeng Huang
- Yuanyuan Xiao
- Fang Xiao
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Affiliations: Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China, Department of Health Toxicology, Xiangya School of Public Health, Central South University, Changsha, Hunan 410078, P.R. China
Published online on: November 29, 2018 https://doi.org/10.3892/mmr.2018.9704
Pages: 1256-1265

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Abstract

Although it is well reported that mitochondrial damage and endoplasmic reticulum (ER) stress (ERS) are involved in heavy metal‑induced cytotoxicity, the role of mitochondrial damage in hexavalent chromium [Cr(VI)]‑induced ERS and the correlation between the two have not been described and remain to be elucidated. The present study evaluated the ability of Cr(VI) to induce ERS in L‑02 hepatocytes, and subsequently examined the role of reactive oxygen species (ROS)‑mediated mitochondrial damage in Cr(VI)‑induced ERS. The findings demonstrated that Cr(VI) induced ERS, which was characterized by the upregulation of ERS‑associated genes and the substantial release of Ca2+ from the ER. The Cr(VI)‑induced mitochondrial production of ROS, by disturbing mitochondrial respiratory chain complexes I and II, may damage mitochondria directly by inducing mitochondrial permeability transition pore opening and mitochondrial membrane potential collapse. The results additionally demonstrated that Cr(VI) induced Ca2+ release from the ER through ROS/caveolin‑1/protein kinase B/inositol 1,4,5‑trisphosphate receptor signaling. The application of the ROS scavenger N‑acetyl‑cysteine confirmed the role of ROS in Cr(VI)‑mediated mitochondrial damage, ERS and apoptotic cell death. The data obtained demonstrated the role of mitochondrial damage in Cr(VI)‑induced ERS and provide novel insight into the elucidation of Cr(VI)‑induced cytotoxicity.

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