Bcl-2 inhibition of neural death: decreased generation of reactive oxygen species.
The proto-oncogene bcl-2 inhibits apoptotic and necrotic neural cell death. Expression of Bcl-2 in the GT1-7 neural cell line prevented death as a result of glutathione depletion. Intracellular reactive oxygen species and lipid peroxides rose rapidly in control cells depleted of glutathione, whereas cells expressing Bcl-2 displayed a blunted increase and complete survival. Modulation of the increase in reactive oxygen species influenced the degree of cell death. Yeast mutants null for superoxide dismutase were partially rescued by expression of Bcl-2. Thus, Bcl-2 prevents cell death by decreasing the net cellular generation of reactive oxygen species.
Kane
D J
DJ
Department of Neurology, University of California, Los Angeles 90024.
Sarafian
T A
TA
Anton
R
R
Hahn
H
H
Gralla
E B
EB
Valentine
J S
JS
Ord
T
T
Bredesen
D E
DE
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D019328:Buthionine Sulfoximine; D016923:Cell Death; D002460:Cell Line; D005978:Glutathione / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D015227:Lipid Peroxidation; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D008717:Methionine Sulfoximine; D017665:Hydroxyl Radical; D019328:Buthionine Sulfoximine; D007501:Iron; D013482:Superoxide Dismutase; D005978:Glutathione