PMID:9681465

Citation	Hochman, A, Sternin, H, Gorodin, S, Korsmeyer, S, Ziv, I, Melamed, E and Offen, D (1998) Enhanced oxidative stress and altered antioxidants in brains of Bcl-2-deficient mice. J. Neurochem. 71:741-8
Abstract	Bcl-2 is an antiapoptotic protein located in the outer mitochondrial membrane. Cellular perturbations associated with programmed cell death may be the consequence of disrupted mitochondrial function as well as excessive production of reactive oxygen species (ROS). Numerous studies indicate that Bcl-2 is involved in opposing cell death induced by oxidative stimuli, but its mode of action is uncertain. We reexamined the role of Bcl-2 by using a loss-of-function model, Bcl-2 knockout mice. Brains from Bcl-2-deficient mice had a 43% higher content of oxidized proteins and 27% lower number of cells in the cerebellum relative to wild-type mice. Incubation of cerebellar neurons from Bcl-2 +/+ brains with 0.5 mM dopamine caused 25% cell death, whereas in Bcl-2-deficient cells, it resulted in 52% death; glial cells provided protection in both cultures. Splenocytes from Bcl-2-deficient mice were also killed more effectively by dopamine as well as paraquat. Bcl-2-deficient mice did not survive intraperitoneal injection of MPTP, which caused a decrease in dopamine level in the striatum of Bcl-2 +/- brains, which was more significant than in wild-type mice. When compared with Bcl-2 +/+ brains, brains of 8-day-old Bcl-2-deficient mice had higher activities of the antioxidant enzymes GSH reductase (192%) and GSH transferase (142%), whereas at the age of 30 days, GSH peroxidase was significantly lower (66%). Activities of GSH transferase and GSH reductase increased significantly (158 and 262%, respectively) from day 8 to day 30 in Bcl-2 +/+ mice, whereas GSH peroxidase decreased (31%) significantly in Bcl-2 -/- animals. In summary, our results demonstrated enhanced oxidative stress and susceptibility to oxidants as well as altered levels of antioxidant enzymes in brains of Bcl-2-deficient mice. It is concluded that Bcl-2 affects cellular levels of ROS, which may be due to an effect either on their production or on antioxidant pathways.
Links	PubMed
Keywords	Animals; Cells, Cultured; Cerebellum/cytology; Corpus Striatum/chemistry; Corpus Striatum/enzymology; Dopamine/analysis; Glutathione Peroxidase/metabolism; Glutathione Reductase/metabolism; Glutathione Transferase/metabolism; Mice; Mice, Knockout/metabolism; Mutagenesis/physiology; Neurons/cytology; Neurons/drug effects; Neurons/enzymology; Oxidants/pharmacology; Oxidative Stress/physiology; Phenotype; Proto-Oncogene Proteins c-bcl-2/genetics; Spleen/cytology
edit table

Annotations

Gene product	Qualifier	GO ID	GO term name	Evidence Code	with/from	Aspect	Notes	Status
edit table

References

See Help:References for how to manage references in GONUTS.