Erythrocytes fail to induce glutathione in response to diethyl maleate or hyperoxia.
We have previously found that exposure of pulmonary artery endothelial cells to hyperoxia or low concentrations of diethyl maleate (DEM) results in elevation of both cellular glutathione (GSH) and uptakes of glutamate and cystine. The present study confirms that this elevation occurs for a variety of lung cells (bovine pulmonary artery endothelial and smooth muscle cells and rat lung fibroblast and epithelial-like cells) but not for human, rat, and chicken erythrocytes. In fact, human and rat erythrocyte GSH levels were reduced substantially at DEM concentrations from 0.05 to 0.5 mM, whereas the GSH level of chicken erythrocytes was almost totally eliminated by 0.05 mM DEM. Also, all erythrocytes failed to accumulate measurable amounts of radioactive glutamate or cystine. The findings suggest the presence of different mechanisms for the regulation of cellular GSH in lung cells from those of erythrocytes. They are consistent with a requirement for a cystine-glutamate transporter and transcriptional and translational events for the elevation of cellular GSH in response to hyperoxia or low levels of DEM in the lung cells.
Phelps
D T
DT
Department of Medicine, Tufts-New England Medical Center, Boston, Massachusetts 02111.
Deneke
S M
SM
Baxter
D F
DF
Fanburg
B L
BL
D000818:Animals; D002417:Cattle; D002460:Cell Line; D002478:Cells, Cultured; D002645:Chickens; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004912:Erythrocytes / Q000502:physiology*; D005978:Glutathione / Q000096:biosynthesis* / Q000097:blood; D006801:Humans; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008298:Maleates / Q000494:pharmacology*; D010100:Oxygen / Q000494:pharmacology*; D011651:Pulmonary Artery; D051381:Rats; D013045:Species Specificity
D008298:Maleates; C014476:diethyl maleate; D005978:Glutathione; D010100:Oxygen