title: Apoptosis in arsenic trioxide-treated Calu-6 lung cells is correlated with the depletion of GSH levels rather than the changes of ROS levels.
abstract: Arsenic trioxide (ATO) can regulate many biological functions such as apoptosis and differentiation in various cells. We investigated an involvement of ROS such as H(2)O(2) and O(2)(*-), and GSH in ATO-treated Calu-6 cell death. The levels of intracellular H(2)O(2) were decreased in ATO-treated Calu-6 cells at 72 h. However, the levels of O(2)(*-) were significantly increased. ATO reduced the intracellular GSH content. Many of the cells having depleted GSH contents were dead, as evidenced by the propidium iodine staining. The activity of CuZn-SOD was strongly down-regulated by ATO at 72 h while the activity of Mn-SOD was weakly up-regulated. The activity of catalase was decreased by ATO. ROS scavengers, Tiron and Trimetazidine did not reduce levels of apoptosis and intracellular O(2)(*-) in ATO-treated Calu-6 cells. Tempol showing a decrease in intracellular O(2)(*-) levels reduced the loss of mitochondrial transmembrane potential (DeltaPsi(m)). Treatment with NAC showing the recovery of GSH depletion and the decreased effect on O(2)(*-) levels in ATO-treated cells significantly inhibited apoptosis. In addition, BSO significantly increased the depletion of GSH content and apoptosis in ATO-treated cells. Treatment with SOD and catalase significantly reduced the levels of O(2)(*-) levels in ATO-treated cells, but did not inhibit apoptosis along with non-effect on the recovery of GSH depletion. Taken together, our results suggest that ATO induces apoptosis in Calu-6 cells via the depletion of the intracellular GSH contents rather than the changes of ROS levels.
authors.affiliation: Department of Physiology, Medical School, Research Institute of Clinical Medicine, Centers for Healthcare Technology Development, Chonbuk National University, JeonJu 561-180, Republic of Korea.
authors.forename: Yong Hwan
authors.initials: YH
authors.lastname: Han
authors.forename: Suhn Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Sung Zoo
authors.initials: SZ
authors.lastname: Kim
authors.forename: Woo Hyun
authors.initials: WH
authors.lastname: Park
mesh_terms: D017209:Apoptosis; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008168:Lung / Q000166:cytology*; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism; D010087:Oxides / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
chemical_list: D001152:Arsenicals; D010087:Oxides; D017382:Reactive Oxygen Species; D004247:DNA; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D000077237:Arsenic Trioxide; D010100:Oxygen