Glutathione depletion inhibits IL-1 beta-stimulated nitric oxide production by reducing inducible nitric oxide synthase gene expression.
L-buthionine-S,R-sulfoximine (BSO), an inhibitor of GSH synthesis, decreased IL-1 beta-induced nitrite release in rat islets and purified rat beta cells, nitrite formation and iNOS gene promoter activity in insulinoma cells, and iNOS mRNA expression in rat islets. The thiol depletor diethyl maleate (DEM) and an inhibitor of glutathione reductase 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) reduced IL-1 beta-stimulated nitrite release in islets. We conclude that GSH regulates IL-1 beta-induced NO production in islets, purified beta cells and insulinoma cells by modulation of iNOS gene expression.
Nikulina
M A
MA
Steno Diabetes Center, Gentofte, Denmark.
Andersen
H U
HU
Karlsen
A E
AE
Darville
M I
MI
Eizirik
D L
DL
Mandrup-Poulsen
T
T
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002330:Carmustine / Q000494:pharmacology; D002469:Cell Separation; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects*; D005978:Glutathione / Q000494:pharmacology / Q000502:physiology*; D007328:Insulin / Q000378:metabolism; D007340:Insulinoma / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008298:Maleates / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D018906:Antineoplastic Agents, Alkylating; D004791:Enzyme Inhibitors; D007328:Insulin; D007375:Interleukin-1; D008298:Maleates; D009573:Nitrites; D012333:RNA, Messenger; D009569:Nitric Oxide; D019328:Buthionine Sulfoximine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C014476:diethyl maleate; D005978:Glutathione; D002330:Carmustine