title: Evidence against the hypothesis that BCL-2 inhibits apoptosis through an anti-oxidant effect.
abstract: We contrasted possible protection against apoptosis afforded by either BCL-2 expression or anti-oxidant inhibitors in the same tumor target challenged by two distinct triggers of apoptosis. Exposure of L929 fibroblasts to tumor necrosis factor (TNF) or etoposide (VP-16) induced apoptotic death with similar kinetics. Enforced expression of BCL-2 significantly protected against apoptosis induced by VP-16 but had no effect against TNF-induced apoptosis. In contrast, the anti-oxidants desferrioxamine, butylated hydroxyanisol and N-acetyl cysteine all inhibited TNF-induced apoptosis in a concentration-dependent fashion. Although exposure to VP-16 resulted in a significant generation of intracellular oxyradicals, the above three anti-oxidant inhibitors had no effect on VP-16-induced apoptotic death. Interestingly, enforced expression of BCL-2 also inhibited the ability of VP-16 to generate oxy-radicals and to depress intracellular glutathione levels. These results indicate that BCL-2 can exert anti-oxidant effects but argue against the hypothesis that these effects are critical to its protection against apoptosis.
authors.affiliation: Department of Medicine, VA West Los Angeles Hospital-UCLA Medical Center, Los Angeles, California, USA.
authors.forename: A
authors.initials: A
authors.lastname: Gardner
authors.forename: F H
authors.initials: FH
authors.lastname: Xu
authors.forename: C
authors.initials: C
authors.lastname: Fady
authors.forename: T
authors.initials: T
authors.lastname: Sarafian
authors.forename: Y
authors.initials: Y
authors.lastname: Tu
authors.forename: A
authors.initials: A
authors.lastname: Lichtenstein