title: Cr(VI) induces the decrease of ATP level and the increase of apoptosis rate mediated by ROS or VDAC1 in L-02 hepatocytes.
abstract: The present study explored the ability of the voltage-dependent anion channel 1 (VDAC1) mRNA and ROS levels to modulate the effects of hexavalent chromium Cr(VI) on the adenosine triphosphate (ATP) level and the rate of apoptotic cell death. Cultured L-02 cells were pretreated with 20mM N-acetyl-cysteine (NAC) for 24h or transiently transfected with small interfering RNAs targeting VDAC1 (siVDAC1) for 48h; cells that were not pretreated were used as the control. The cells were subsequently treated with 0, 2, 8, or 32μM Cr(VI) for 24h. Then, levels of VDAC1 mRNA, ROS, and ATP and the apoptosis rate were measured by reverse-transcription quantitative PCR, fluorometry, a bioluminescence assay, and flow cytometry, respectively. The results showed that Cr(VI) at 32μM led to increase in the ROS level, VDAC1 mRNA expression, and the apoptosis rate and a decrease in the ATP level; pretreatment with NAC led to the down-regulation in the levels of ROS, VDAC1 mRNA and apoptosis and the significant up-regulation in the ATP levels. Interestingly, after the pretreatment with siVDAC1 to inhibit VDAC1 mRNA expression, the increased apoptosis rates and decreased ATP levels were reversed as well. These results suggested that changes in the ROS or VDAC1 mRNA levels were associated with changes in the ATP level and apoptosis rate. Furthermore, correlation analysis confirmed the association between both the ROS and VDAC1 levels and both the ATP level and the apoptosis rate. In conclusion, Cr(VI) induced ROS- and VDAC1-mediated decreases in ATP levels and increases in the apoptosis rate.
authors.affiliation: Department of Health Toxicology, School of Public Health, Central South University, Changsha, Hunan 410078, China; Department of Clinical Laboratory, Huaihua Medical College, Huaihua, Hunan 418000, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Health Toxicology, School of Public Health, Central South University, Changsha, Hunan 410078, China.
authors.forename: Zen
authors.initials: Z
authors.lastname: Ming
authors.affiliation: Department of Health Toxicology, School of Public Health, Central South University, Changsha, Hunan 410078, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Gong-Hua
authors.affiliation: Department of Health Toxicology, School of Public Health, Central South University, Changsha, Hunan 410078, China.
authors.forename: Guan
authors.initials: G
authors.lastname: Lan
authors.affiliation: Department of Health Toxicology, School of Public Health, Central South University, Changsha, Hunan 410078, China.
authors.forename: Dai
authors.initials: D
authors.lastname: Lu
authors.affiliation: Department of Health Toxicology, School of Public Health, Central South University, Changsha, Hunan 410078, China.
authors.forename: Li
authors.initials: L
authors.lastname: Peng
authors.affiliation: Department of Health Toxicology, School of Public Health, Central South University, Changsha, Hunan 410078, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Health Toxicology, School of Public Health, Central South University, Changsha, Hunan 410078, China. Electronic address: zcg54@xysm.net.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Cai-Gao
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002857:Chromium / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D050995:Voltage-Dependent Anion Channel 1 / Q000235:genetics*
chemical_list: D002273:Carcinogens; D004785:Environmental Pollutants; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C494762:VDAC1 protein, human; D002857:Chromium; C074702:chromium hexavalent ion; D000255:Adenosine Triphosphate; D050995:Voltage-Dependent Anion Channel 1