Specific role of an α,β-unsaturated carbonyl group in γ-glutamylcysteine synthetase induction by prostaglandin A 2

The effects of prostaglandins (PGs) on cellular glutathione (GSH) status in L-1210 cells were examined. PGA 2 and J 2, which have an α,β-unsaturated carbonyl group in the cyclopentane ring, elevated the GSH content, but PGB 2, D 2, E 2 and F 2α did not show the effect. When L-1210 cells were incubated with various 2-cyclopentenone derivatives, 4-hydroxy-2-cyclopentenone and some of related compounds elevated cellular GSH levels. Subsequent study with cell-free extract of cultured L-1210 cells revealed that PGA 2 and 4-hydroxy-2-cyclopentenone induced γ-glutamylcysteine synthetase activity at the transcriptional level. This induction was also found in other cultured mammalian cells such as HeLa S3, NIH/3T3 and porcine aorta endothelial cells. When L-1210 cells were incubated with PGA 2 in the presence of 4-hydroxy-2-cyclopentenone and its analogues, they inhibited the accumulation of PGA 2 in cell nuclei. Our findings thus suggest that an α,β-unsaturated carbonyl moiety is responsible for enhancing the biosynthesis of γ-glutamylcysteine synthetase in cultured cells.