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 (NaAsO2), arsenic trioxide (AS(2)O(3)) or sodium arsenate (Na2HAsO4) up to 72 hr at 0, 1, 5, and 10 mu M, respectively. Intracellular GSH and glutathione disulficle (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 24 hr 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. Na2HAsO4 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 As2O3-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. (C) 2008 Elsevier Ltd. All rights reserved.