Inhibitory effect of an intracellular glutathione on delta 12-prostaglandin J2-induced protein syntheses in porcine aortic endothelial cells.
Delta 12-Prostaglandin (PG) J2 caused porcine aortic endothelial cells to synthesize a 31,000-dalton heme oxygenase and a 67,000-dalton protein (p67). Treatment of the cells with buthionine sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis, depleted intracellular GSH, and enhanced the induction of heme oxygenase and p67 syntheses by delta 12-PGJ2. In contrast, treatment with GSH increased the intracellular GSH level and reduced the induction. There was a reciprocal relationship between the level of intracellular GSH, and that of the induction of heme oxygenase and p67 syntheses by delta 12-PGJ2. An increase in the intracellular GSH level caused an increase in the ethyl acetate-unextractable form of delta 12-PGJ2 in the cytosol, but suppressed the accumulation of delta 12-PGJ2 in the nuclei. Furthermore, GSH strongly inhibited the in vitro binding of delta 12-PGJ2 to isolated nuclei, which is N-ethylmaleimide sensitive. Moreover, the induction of heme oxygenase and p67 syntheses by the thiol-reactive agents arsenite and diethylmaleate was also inhibited by GSH treatment and enhanced by BSO treatment. These results demonstrate that intracellular GSH suppresses delta 12-PGJ2-induced heme oxygenase and p67 syntheses by inhibiting the binding of delta 12-PGJ2 to nuclei.
Koizumi
T
T
Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Negishi
M
M
Ichikawa
A
A
D000818:Animals; D001011:Aorta; D001151:Arsenic / Q000494:pharmacology; D018053:Arsenites; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects*; D005978:Glutathione / Q000494:pharmacology*; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D008298:Maleates / Q000494:pharmacology; D009687:Nuclear Proteins / Q000096:biosynthesis*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D026362:Serum Response Factor; D013552:Swine
D018053:Arsenites; D004268:DNA-Binding Proteins; D008298:Maleates; D009687:Nuclear Proteins; D026362:Serum Response Factor; C037112:9-deoxy-delta-9-prostaglandin D2; D006419:Heme Oxygenase (Decyclizing); C014476:diethyl maleate; D005978:Glutathione; C015001:arsenite; D001151:Arsenic; D015230:Prostaglandin D2