CoQ10 Deficiency May Indicate Mitochondrial Dysfunction in Cr(VI) Toxicity

• Published in: International journal of molecular sciences Vol. 18; no. 4; p. 816
• Main Authors: Zhong, Xiali, Yi, Xing, da Silveira E Sá, Rita de Cássia, Zhang, Yujing, Liu, Kaihua, Xiao, Fang, Zhong, Caigao
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24-04-2017; MDPI
• Subjects: Adenosine Triphosphate - metabolism; Aldehydes; Apoptosis; Apoptosis - drug effects; Bcl-2 protein; bcl-2-Associated X Protein - metabolism; Calcium - metabolism; Calcium ions; Calcium permeability; Caspase 3 - metabolism; Caspase 9 - metabolism; Caspase-3; Caspase-9; Cell Line; Cell Survival - drug effects; Chromium - toxicity; coenzyme Q10; Copy number; Cytochromes c - metabolism; Cytotoxicity; Depolarization; DNA, Mitochondrial - metabolism; Electron transfer; Exposure; Gene expression; Hepatocytes; Hexavalent chromium; hexavalent chromium Cr(VI); Humans; L-02 hepatocytes; Membrane permeability; Membrane potential; Membrane Potential, Mitochondrial - drug effects; Mitochondria - drug effects; Mitochondria - genetics; Mitochondria - metabolism; Mitochondrial DNA; mitochondrial membrane potential (MMP); Mitochondrial permeability transition pore; Oxidative Stress - drug effects; Proto-Oncogene Proteins c-bcl-2 - analysis; Proto-Oncogene Proteins c-bcl-2 - metabolism; reactive oxygen species (ROS); Reactive Oxygen Species - metabolism; Recovery of function; Spectrometry, Fluorescence; Superoxide dismutase; Superoxide Dismutase - metabolism; Ubiquinone - analogs & derivatives; Ubiquinone - analysis; Ubiquinone - metabolism; Ubiquinone - pharmacology; L-02 hepatocytes; apoptosis; coenzyme Q10; reactive oxygen species (ROS); hexavalent chromium Cr(VI); mitochondrial membrane potential (MMP)
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms18040816

To investigate the toxic mechanism of hexavalent chromium Cr(VI) and search for an antidote for Cr(VI)-induced cytotoxicity, a study of mitochondrial dysfunction induced by Cr(VI) and cell survival by recovering mitochondrial function was performed. In the present study, we found that the gene expression of electron transfer flavoprotein dehydrogenase (ETFDH) was strongly downregulated by Cr(VI) exposure. The levels of coenzyme 10 (CoQ10) and mitochondrial biogenesis presented by mitochondrial mass and mitochondrial DNA copy number were also significantly reduced after Cr(VI) exposure. The subsequent, Cr(VI)-induced mitochondrial damage and apoptosis were characterized by reactive oxygen species (ROS) accumulation, caspase-3 and caspase-9 activation, decreased superoxide dismutase (SOD) and ATP production, increased methane dicarboxylic aldehyde (MDA) content, mitochondrial membrane depolarization and mitochondrial permeability transition pore (MPTP) opening, increased Ca
levels, Cyt c release, decreased Bcl-2 expression, and significantly elevated Bax expression. The Cr(VI)-induced deleterious changes were attenuated by pretreatment with CoQ10 in L-02 hepatocytes. These data suggest that Cr(VI) induces CoQ10 deficiency in L-02 hepatocytes, indicating that this deficiency may be a biomarker of mitochondrial dysfunction in Cr(VI) poisoning and that exogenous administration of CoQ10 may restore mitochondrial function and protect the liver from Cr(VI) exposure.