Glutathione levels determine apoptosis in macrophages.
Spermine NONOate (SpNO, a nitric oxide donor) induced apoptosis and caspase-3 activity in the macrophage cell line RAW 267.4. RES cells that have been derived from RAW 267.4 cells by repeated exposure to lipopolysaccharide and interferon-gamma (LPS/INF-gamma), followed by outgrowth of viable cells, are resistant to apoptosis and caspase-3 activation upon exposure to SpNO. In this study we have determined that RES cells have lower levels of glutathione (GSH) and a higher oxidative state than RAW cells. Subsequently, RAW and RES cells were depleted of GSH by using l-buthionine-[S,R]-sulfoximine (BSO), a specific inhibitor of GSH synthesis. GSH depleted cells did not undergo apoptosis nor demonstrate caspase-3 activity when they were exposed to SpNO. These results suggest that the redox status of the cell is one of the key factors mediating the apoptotic pathway in which glutathione plays a critical role in mediating apoptosis via NO* and reactive oxygen species (ROS).
Boggs
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Molecular Cardiovascular Research Center, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, Ohio, 44106-4958, USA.
McCormick
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Lapetina
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D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D009589:Nitrogen Oxides; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D013096:Spermine / Q000031:analogs & derivatives / Q000494:pharmacology
D009589:Nitrogen Oxides; D017382:Reactive Oxygen Species; C091861:spermine nitric oxide complex; D013096:Spermine; D009569:Nitric Oxide; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D005978:Glutathione