Differential influences of various arsenic compounds on glutathione redox status and antioxidative enzymes in porcine endothelial cells.
The cellular response and detoxification mechanisms in porcine endothelial cells (PAECs) to arsenic trioxide (As2O3), sodium arsenite (NaAsO2) and sodium arsenate (Na2HAsO4) were investigated. NaAsO2 at 20 microM for 72 h increased Cu/Zn superoxide dismutase activity resulting in elevated intracellular hydrogen peroxide levels, but As2O3 and Na2HAsO4 did not. Trivalent arsenic compounds increased intracellular oxidized glutathione (GSSG) and total glutathione (GSH) and cellular glutathione peroxidase (cGPX) and glutathione S-transferase (GST) activity, but not glutathione reductase activity. The increased cGPX activity resulted in an elevated cellular GSSG content. Na2HAsO4 increased the cellular GSSG level at 72 h compared to controls. These results imply that the increased GSH content responding to the oxidative stress by trivalent arsenic compounds may be mainly related to the regulation of GSH turnover. The increased GST activity implies that the elevated intracellular GSH level responding to the oxidative stress may be used to conjugate arsenic in PAECs and facilitate arsenic efflux.
Yeh
J Y
JY
Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Room 108, Medical Research Building, 100 Shih-Chuan 1st Road, Kaohsiung, 807, Taiwan, ROC. jyyeh@nhri.org.tw
Cheng
L C
LC
Ou
B R
BR
Whanger
D P
DP
Chang
L W
LW
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001151:Arsenic / Q000378:metabolism; D001152:Arsenicals / Q000494:pharmacology*; D015153:Blotting, Western; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D019803:Glutathione Disulfide / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D013439:Sulfhydryl Reagents / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000187:drug effects; D013552:Swine
D000975:Antioxidants; D001152:Arsenicals; D013439:Sulfhydryl Reagents; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D005978:Glutathione; D001151:Arsenic; D019803:Glutathione Disulfide