Abstract
Prostaglandin A2 (PGA2) was found to stimulate the gene expression of yglutamylcysteine synthetase (γ-GCS), a key enzyme of glutathione (GSH) biosynthesis, and modify the cellular GSH levels of L-1210 murine leukemia cells. PGJ2 also enhanced the GSH production, but PGB2, D2, E2 and F2α were ineffective, suggesting that the a, fl-unsaturated carbonyl is essential for the enzyme induction. This inducing activity was generally observed with HeLa S3, NIH/3T3 and porcine aorta endothelial cells, and was not related to a previously disclosed function that PGA2 blocks the cell cycle progression at G, stage. Carrier-mediated transport of PGA2 to cell nuclei was confirmed with intact cell and cell-free system. Nuclear binding of PGA2 and expression of biological activity were found to be closely correlated. Induction of γ-GCS was effective for protecting vascular endothelial cells from oxidative stress produced by menadjone. Present study suggests the possibility that PGA2 is involved in regulating the physiological functions of cells by affecting the GSH status.
