Human Bcl-2 Reverses Survival Defects in Yeast Lacking
Superoxide Dismutase and Delays Death of Wild-Type Yeast |
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| Authors: | Valter D Longo Lisa M Ellerby Dale E Bredesen Joan S Valentine and Edith B Gralla |
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| Institution: | *Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, California 90095-1569; ?Program on Aging, The Burnham Institute, La Jolla, California 92037; and §Neuroscience Department, University of California at San Diego, La Jolla, California 92093 |
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| Abstract: | We expressed the human anti-apoptotic protein, Bcl-2, in Saccharomyces cerevisiae to investigate its effects on antioxidant protection and stationary phase survival. Yeast lacking copper-zinc superoxide dismutase (sod1Δ) show a profound defect in entry into and survival during stationary phase even under conditions optimal for survival of wild-type strains (incubation in water after stationary phase is reached). Expression of Bcl-2 in the sod1Δ strain caused a large improvement in viability at entry into stationary phase, as well as increased resistance to 100% oxygen and increased catalase activity. In addition, Bcl-2 expression reduced mutation frequency in both wild-type and sod1Δ strains. In another set of experiments, wild-type yeast incubated in expired minimal medium instead of water lost viability quickly; expression of Bcl-2 significantly delayed this stationary phase death. Our results demonstrate that Bcl-2 has activities in yeast that are similar to activities it is known to possess in mammalian cells: (a) stimulation of antioxidant protection and (b) delay of processes leading to cell death. |
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