Effect of intracellular glutathione on the production of prostaglandin D2 in RBL-2H3 cells oxidized by tert-butyl hydroperoxide.
The liberation of arachidonic acid and the production of prostaglandin D2 (PGD2) were significantly influenced by peroxide and the level of intracellular glutathione (GSH). The productions of free arachidonic acid and PGD2 in RBL-2H3 cells were enhanced considerably by exposure to tert-butyl hydroperoxide (t-BHP). The liberation of arachidonic acid induced by t-BHP was not inhibited by EGTA. The productions of PGD2 and arachidonic acid induced by t-BHP were significantly facilitated by the depletion of intracellular GSH using buthionine sulfoximine (BSO) or diethyl maleate (DEM), although the depletion of GSH had no effect on the production of PGD2 induced by A23187. t-BHP failed to activate the conversion of free arachidonic acid to PGD2, since the formation of PGD2 from exogenously added arachidonic acid was not enhanced by treatment with t-BHP. The level of lipid hydroperoxides in t-BHP-treated cells was significantly elevated by treatment with DEM. These results suggest that hydroperoxides increase the free arachidonic acid available for the synthesis of PGD2 by activating phospholipase A2 (PLA2) and that the depletion of GSH by DEM accelerates the activation of PLA2 by raising peroxide levels in cells. Thus, the observed alterations in GSH levels are large enough to cause increased PGD2 synthesis in RBL-2H3 cells exposed to oxidative stress.
Sakamoto
H
H
School of Pharmaceutical Sciences, Kitasato University, Minato-ku, Tokyo, 108-8641, Japan.
Kitahara
J
J
Nakagawa
Y
Y
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D051545:Cyclooxygenase 1; D005978:Glutathione / Q000378:metabolism*; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D007942:Leukemia, Experimental / Q000188:drug therapy / Q000378:metabolism*; D054834:Lipocalins; D008298:Maleates / Q000494:pharmacology; D008565:Membrane Proteins; D016877:Oxidants / Q000378:metabolism / Q000494:pharmacology; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D015230:Prostaglandin D2 / Q000096:biosynthesis*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured; D020122:tert-Butylhydroperoxide / Q000378:metabolism* / Q000494:pharmacology
D007476:Ionophores; D007527:Isoenzymes; D054834:Lipocalins; D008298:Maleates; D008565:Membrane Proteins; D016877:Oxidants; D010743:Phospholipids; D016718:Arachidonic Acid; D000001:Calcimycin; D019328:Buthionine Sulfoximine; D020122:tert-Butylhydroperoxide; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; C014476:diethyl maleate; D005978:Glutathione; D015230:Prostaglandin D2