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• W2085294253 abstract "Normal mouse embryo fibroblasts (MEF) are killed by treatment with low doses of interferon γ (IFN-γ) in combination with lipopolysaccharide (LPS). This cytotoxicity has previously been shown to represent an active suicidal reaction. Here we show that the time period between first contact with IFN-γ/LPS (t= 0 h) and cell death (t= 48 h) can be separated into two distinct periods, during which glycolytic metabolism of glucose either has a positive (8–24 h) or a negative (30–48 h) effect on cytotoxicity. During the first period (8–24 h), withdrawal of glucose from the culture medium, or inclusion in the medium of the glycolytic inhibitors deoxy-d-glucose, NaF or iodoacetate, prevented later cell death. During the second period (30–48 h), withdrawal of glucose or supplementation of the culture medium with glycolytic inhibitors was no longer protective; instead it was a requirement for cell suicide to occur. Glycolytic activity during the first period was found to be increased twofold in LPS-treated MEF and almost threefold in IFN-γ/LPS-treated MEF. A variety of agents were found both to protect cells against IFN-γ/LPS-induced cytotoxicity and to inhibit increased glycolysis in these cells: glucocorticoids, the serine-type protease inhibitor N-acetyl-dl-phenylalanine-β-naphthyl ester, the ADP-ribosylation inhibitors 3-aminobenzamide and nicotinamide, and the transcription and translation inhibitors actinomycin and cycloheximide. Mitochondrial function, although normal in LPS-treated cells, was markedly depressed in IFN-γ/LPS-treated MEF. Specifically, malate- and succinate-driven respiration was found to be impaired. Furthermore, IFN-γ/LPS-treated MEF contained one-third of the ATP level of LPS-treated MEF. Withdrawal of l-arginine from the culture medium prevented cell death in IFN-γ/LPS-treated MEF. N-Methyl-l-arginine, which is an inhibitor of nitric oxide (NO·) biosynthesis from l-arginine, also inhibited cell death. In conclusion, we propose that cell death in our experiments is due to an l-arginine/glycolysis-dependent impairment of mitochondrial respiration." @default.
• W2085294253 created "2016-06-24" @default.
• W2085294253 creator A5054279562 @default.
• W2085294253 creator A5068786256 @default.
• W2085294253 date "1991-11-01" @default.
• W2085294253 modified "2023-09-24" @default.
• W2085294253 title "Interferon-gamma/lipolysaccharide-treated mouse embryonic fibroblasts are killed by a glycolysis/l-arginine-dependent process accompanied by depression of mitochondrial respiration" @default.
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• W2085294253 doi "https://doi.org/10.1111/j.1432-1033.1991.tb16356.x" @default.
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