No 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, BcI-2 knockout mice. Brains from Bc/-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 +1+ brains with 0.5 mM dopamine caused 25% cell death, whereas in Bc!-2-deficient cells, it resulted in 52% death; glial cells provided protection in both cultures. Splenocytes from Bc!-2-deficient mice were also killed more effectively by dopamine as well as paraquat. Bc!-2-deficient mice did not survive intraperitoneal injection of MPTP, which caused a decrease in dopamine level in the striatum of Bc!-2