Bcl-2 family members inhibit oxidative stress-induced programmed cell death in Saccharomyces cerevisiae

Shao Rong Chen, David D. Dunigan, Martin B. Dickman

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

Selected antiapoptotic genes were expressed in baker's yeast (Saccharomyces cerevisiae) to evaluate cytoprotective effects during oxidative stress. When exposed to treatments resulting in the generation of reactive oxygen species (ROS), including H2O2, menadione, or heat shock, wild-type yeast died and exhibited apoptotic-like characteristics, consistent with previous studies. Yeast strains were generated expressing nematode ced-9, human bcl-2, or chicken bcl-xl genes. These transformants tolerated a range of oxidative stresses, did not display features associated with apoptosis, and remained viable under conditions that were lethal to wild-type yeast. Yeast strains expressing a mutant antiapoptotic gene (bcl-2 Δα 5-6), known to be nonfunctional in mammalian cells, were unable to tolerate any of the ROS-generating insults. These data are the first report showing CED-9 has cytoprotective effects against oxidative stress, and add CED-9 to the list of Bcl-2 protein family members that modulate ROS-mediated programmed cell death. In addition, these data indicate that Bcl-2 family members protect wild-type yeast from physiological stresses. Taken together, these data support the concept of the broad evolutionary conservation and functional similarity of the apoptotic processes in eukaryotic organisms.

Original languageEnglish (US)
Pages (from-to)1315-1325
Number of pages11
JournalFree Radical Biology and Medicine
Volume34
Issue number10
DOIs
StatePublished - May 15 2003

Keywords

  • Apoptosis
  • CED-9
  • Free radicals
  • Heat shock
  • ROS
  • TUNEL
  • Yeast

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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