Glutathione regulation in arsenic-induced porcine aortic endothelial cells.
The objective was to investigate the regulation of glutathione (GSH) turnover in porcine aortic endothelial cells (PAECs) treated with sodium arsenite (NaAsO(2)), arsenic trioxide (As(2)O(3)) or sodium arsenate (Na(2)HAsO(4)) up to 72 hr at 0, 1, 5, and 10 microM, respectively. Intracellular GSH and glutathione disulfide (GSSG) contents, as well as the activities and mRNA levels of glutamate-cysteine lyase (GCL; gamma-glutamylcysteine synthetase) and gamma-glutamyl transpeptidase (GGT), were examined. The trivalent arsenic compounds increased GSH and GSSG contents in PAECs. An increase in GCL activity was observed at 24hr whereas an increase in GCL mRNA level was observed at 72 hr. The increase in GGT activity was only observed at 72 hr. In addition, a tendency of increase in GGT mRNA level was observed. Na(2)HAsO(4) treatment did not affect GSH content and the turnover-related enzymes. A differential GSH modulation in PAECs by trivalent arsenic compounds was found. The regulatory mechanism responsible for the As(2)O(3)-induced GSH increase is related to the GSH-turnover enzymes, GCL and GGT, while that for the NaAsO(2)-induced GSH increase may not be related to expression of GSH-turnover enzymes.
Cheng
Ya-Hsin
YH
Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli 305, Taiwan, ROC.
Ou
Bor-Rung
BR
Cheng
Li-Chuan
LC
Lu
Jian-He
JH
Yeh
Jan-Ying
JY
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects; D001149:Arsenates / Q000633:toxicity*; D000077237:Arsenic Trioxide; D001152:Arsenicals; D018053:Arsenites / Q000633:toxicity*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005721:Glutamate-Cysteine Ligase / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000187:drug effects* / Q000378:metabolism; D019803:Glutathione Disulfide / Q000187:drug effects / Q000378:metabolism; D010087:Oxides / Q000633:toxicity*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D017670:Sodium Compounds / Q000633:toxicity*; D013552:Swine; D013997:Time Factors; D005723:gamma-Glutamyltransferase / Q000187:drug effects / Q000378:metabolism
D001149:Arsenates; D001152:Arsenicals; D018053:Arsenites; D010087:Oxides; D012333:RNA, Messenger; D017670:Sodium Compounds; C017947:sodium arsenite; C009277:sodium arsenate; D005723:gamma-Glutamyltransferase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D000077237:Arsenic Trioxide; D019803:Glutathione Disulfide