PMID: 11329505May 1, 2001Paper

Removal of glutathione produces apoptosis and necrosis in HepG2 cells overexpressing CYP2E1

Alcoholism, Clinical and Experimental Research
D Wu, A I Cederbaum

Abstract

Previous studies have shown that addition of ethanol, iron, or arachidonic acid to HepG2 cells expressing CYP2E1 produced a loss in cell viability and caused apoptosis. These effects were enhanced when cellular reduced glutathione (GSH) levels were lowered by treatment with buthionine sulfoximine (BSO). Overexpression of CYP2E1 in HepG2 cells could produce toxicity even in the absence of added toxin after BSO treatment. Studies were carried out to characterize this CYP2E1-and BSO-dependent toxicity. HepG2 cells expressing CYP2E1 were treated with BSO for 1 to 4 days, and various parameters associated with apoptosis and cell viability were assayed. Treatment of cells expressing CYP2E1 (E47 cells) with BSO resulted in apoptosis as well as necrosis. The apoptosis and necrosis were independent of each other. No toxicity was found with control HepG2 cells or HepG2 cells expressing CYP3A4 instead of CYP2E1 under these conditions. The antioxidant trolox partially prevented the apoptosis and necrosis, whereas diallylsulfide, a CYP2E1 inhibitor, was fully protective. The activity of caspase 3, but not caspases 1, 8, or 9, was increased in the BSO-treated E47 cells, and an inhibitor of caspase 3 prevented apoptosis. Damage to mitochondri...Continue Reading

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