Specific role of an alpha,beta-unsaturated carbonyl group in gamma-glutamylcysteine synthetase induction by prostaglandin A2.
The effects of prostaglandins (PGs) on cellular glutathione (GSH) status in L-1210 cells were examined. PGA2 and J2, which have an alpha,beta-unsaturated carbonyl group in the cyclopentane ring, elevated the GSH content, but PGB2, D2, E2 and F2 alpha 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 PGA2 and 4-hydroxy-2-cyclopentenone induced gamma-glutamycysteine 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 PGA2 in the presence of 4-hydroxy-2-cyclopentenone and its analogues, they inhibited the accumulation of PGA2 in cell nuclei. Our findings thus suggest that an alpha,beta-unsaturated carbonyl moiety is responsible for enhancing the biosynthesis of gamma-glutamylcysteine synthetase in cultured cells.
Ohno
K
K
Shiongi Research Laboratories, Shionogi and Co. Ltd., Osaka, Japan.
Higaki
J
J
Takechi
S
S
Hirata
M
M
D000818:Animals; D002474:Cell-Free System; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D003517:Cyclopentanes / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005721:Glutamate-Cysteine Ligase / Q000096:biosynthesis*; D005978:Glutathione / Q000096:biosynthesis*; D006801:Humans; D007939:Leukemia L1210 / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D010453:Peptide Synthases / Q000096:biosynthesis*; D011454:Prostaglandins A / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013552:Swine; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism
D003517:Cyclopentanes; D011454:Prostaglandins A; C007201:cyclopentanone; D010453:Peptide Synthases; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; C100008:prostaglandin A2