Bcl-2 family members inhibit oxidative stress-induced programmed cell death in Saccharomyces cerevisiae.
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 H(2)O(2), 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 deltaalpha 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.
Department of Plant Pathology, University of Nebraska, Lincoln, NE 68583-0722, USA.
Shao-Rong
SR
Chen
David D
DD
Dunigan
Martin B
MB
Dickman
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D002645:Chickens; D017931:DNA Primers / Q000737:chemistry; D005434:Flow Cytometry; D015870:Gene Expression; D006358:Hot Temperature; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D018384:Oxidative Stress; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D014170:Transformation, Genetic; D024483:Vitamin K 3 / Q000378:metabolism; D051020:bcl-X Protein
D017304:Annexin A5; D051017:Apoptosis Regulatory Proteins; C494811:BCL2L1 protein, human; D029742:Caenorhabditis elegans Proteins; C087233:Ced-9 protein, C elegans; D017931:DNA Primers; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D024483:Vitamin K 3; D006861:Hydrogen Peroxide