THE EFFECT OF PROSTAGLANDIN E-2 ON CYSTINE UPTAKE AND GLUTATHIONE SYNTHESIS BY HUMAN LUNG FIBROBLASTS

Prostaglandin E-2 (PGE(2)) is an inflammatory mediator capable of regu lating fibroblast cell proliferation, matrix protein production, and s ystem A amino acid transport. System x(c)(-) amino acid transport is r egulated by electrophilic agents and oxygen. The effect of PGE(2) on t he x(c)(-) system transport of cystine and the synthesis of glutathion e by human lung fibroblasts was examined. Preincubation of fibroblast cultures with PGE2 decreased cystine uptake by 42%. Kinetic studies re vealed a 42% decrease in the V-max of the x(c)(-) system transporter i n PGE(2)-treated fibroblasts; however, the apparent K-m was not affect ed. The glutathione content of PGE(2)-treated fibroblasts was decrease d by up to 25% of control. These results demonstrate that system x(c)( -) transport of cystine is regulated by PGE? and suggest that the limi ted availability of intracellular cysteine inhibited glutathione synth esis. (C) 1998 Published by Elsevier Science B.V. All rights reserved.