دورية أكاديمية
Role of glutathione in macrophage activation: effect of cellular glutathione depletion on nitrite production and leishmanicidal activity.
| العنوان: | Role of glutathione in macrophage activation: effect of cellular glutathione depletion on nitrite production and leishmanicidal activity. |
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| المؤلفون: | Buchmüller-Rouiller, Y., Corrandin, S.B., Smith, J., Schneider, P., Ransijn, A., Jongeneel, C.V., Mauël, J. |
| المصدر: | Cellular Immunology, vol. 164, no. 1, pp. 73-80 |
| سنة النشر: | 1995 |
| المجموعة: | Université de Lausanne (UNIL): Serval - Serveur académique lausannois |
| مصطلحات موضوعية: | Amino Acid Oxidoreductases/antagonists & inhibitors, Amino Acid Oxidoreductases/genetics, Animals, Buthionine Sulfoximine, Cells, Cultured, Enzyme Inhibitors/pharmacology, Female, Glutathione/deficiency, Glutathione/physiology, Leishmaniasis/prevention & control, Macrophage Activation/drug effects, Male, Maleates/pharmacology, Methionine Sulfoximine/analogs & derivatives, Methionine Sulfoximine/pharmacology, Mice, Inbred CBA, Nitric Oxide/antagonists & inhibitors, Nitric Oxide/biosynthesis, Nitric Oxide Synthase, Nitrites/metabolism, RNA, Messenger/biosynthesis |
| الوصف: | We have examined the effects of two agents depleting the intracellular pool of glutathione (GSH) on macrophage activation induced by IFN-gamma + LPS, as measured by nitrite production and leishmanicidal activity. Diethylmaleate (DEM), which depletes intracellular GSH by conjugation via a reaction catalyzed by the GSH-S-transferase, strongly inhibited nitrite secretion and leishmanicidal activity when added before or at the time of addition of IFN-gamma + LPS; this inhibition was progressively lost when addition of DEM was delayed up to 10 hr. A close correlation was observed between levels of intracellular soluble GSH during activation and nitrite secretion. Inhibition was partially reversed by the addition of glutathione ethyl ester (GSH-Et). Buthionine sulfoximine (BSO), a specific inhibitor of gamma-glutamylcysteine synthetase, also inhibited macrophage activation, although to a lesser extent than DEM despite a more pronounced soluble GSH depletion. This inhibition was completely reversed by the addition of GSH-Et. DEM and BSO did not alter cell viability or PMA-triggered O2- production by activated macrophages, suggesting that the inhibitory effects observed on nitrite secretion and leishmanicidal activity were not related to a general impairment of macrophage function. DEM and BSO treatment reduced iNOS specific activity and iNOS protein in cytosolic extracts. DEM also decreased iNOS mRNA expression while BSO had no effect. Although commonly used as a GSH-depleting agent, DEM may have additional effects because it can also act as a sulhydryl reagent; BSO, on the other hand, which depletes GSH by enzymatic inhibition, has no effect on protein-bound GSH. Our results suggest that both soluble and protein-bound GSH may be important for the induction of NO synthase in IFN-gamma + LPS-activated macrophages. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0008-8749 |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/7543373; info:eu-repo/semantics/altIdentifier/pissn/0008-8749; https://serval.unil.ch/notice/serval:BIB_2627A5DF2223Test; urn:issn:0008-8749 |
| DOI: | 10.1006/cimm.1995.1144 |
| الإتاحة: | https://doi.org/10.1006/cimm.1995.1144Test https://serval.unil.ch/notice/serval:BIB_2627A5DF2223Test |
| رقم الانضمام: | edsbas.EC619F4E |
| قاعدة البيانات: | BASE |
| تدمد: | 00088749 |
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| DOI: | 10.1006/cimm.1995.1144 |