Human Bcl-2 reverses survival defects in yeast lacking superoxide dismutase and delays death of wild-type yeast.
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 (sod1Delta) 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 sod1Delta 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 sod1Delta 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.
Longo
V D
VD
Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, California 90095-1569, USA.
Ellerby
L M
LM
Bredesen
D E
DE
Valentine
J S
JS
Gralla
E B
EB
D015966:Gene Expression Regulation, Fungal; D018014:Gene Transfer Techniques; D006801:Humans; D009154:Mutation; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development; D013482:Superoxide Dismutase / Q000235:genetics*
D019253:Proto-Oncogene Proteins c-bcl-2; D013482:Superoxide Dismutase