Induction of cystine transport in bovine pulmonary artery endothelial cells by sodium arsenite.
Sodium arsenite is one of a number of agents reported to induce a 30-34 kDa 'stress' protein in cells. Other agents which induce this stress protein, including diethyl maleate (DEM) and H2O2, have also been reported to be inducers of cystine transport in fibroblasts, macrophages, endothelial cells and other cell types. We have determined that micromolar levels of sodium arsenite increase cystine transport in bovine pulmonary artery endothelial cells (BPAEC), resulting in increases in intracellular glutathione (GSH). The increase in cystine transport appears to be due to stimulation of the synthesis of a protein analogous to the xc- transport system, a sodium-independent system specific for cystine and glutamate. We have determined that this stimulation is maximal between 8-16 h after addition of sodium arsenite and is inhibited by exogenous GSH. Others have reported that synthesis of the 30-34 kDa stress protein is maximal between 2-4 h and returns to baseline by 6-10 h. We conclude that cystine transport may be considered a 'secondary' stress response and is likely to be modulated by sulfhydryl-reactive agents.
Deneke
S M
SM
Department of Medicine (Pulmonary Diseases/Critical Care), University of Texas Health Science Center San Antonio 78284-7885.
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001151:Arsenic / Q000494:pharmacology*; D018053:Arsenites; D001692:Biological Transport / Q000187:drug effects; D002417:Cattle; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003553:Cystine / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D007700:Kinetics; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism; D017670:Sodium Compounds; D013439:Sulfhydryl Reagents / Q000494:pharmacology*
D000596:Amino Acids; D018053:Arsenites; D017670:Sodium Compounds; D013439:Sulfhydryl Reagents; C017947:sodium arsenite; D003553:Cystine; D003513:Cycloheximide; D005978:Glutathione; D001151:Arsenic