Selective oxidation and externalization of membrane phosphatidylserine: Bcl-2-induced potentiation of the final common pathway for apoptosis

The induction of apoptosis in PC12 cells by the enediyne neocarzinostatin ( NCS) is paradoxically potentiated by overexpression of bcl-2. The enhanced activation of NCS seen in bcl-2-overexpressing cells cannot by itself be re sponsible for the potentiation of apoptosis, since Bcl-2 would be expected to block; apoptosis at a point distal to NCS activation (e.g., in the apopt osis final common pathway). We now report that overexpression of bcl-2 in P C12 cells does not protect the cells from NCS-induced oxidation of membrane phosphatidylserine (PS), and results in potentiation of NCS-induced extern alization of membrane PS, two events associated with the apoptosis final co mmon pathway. The mechanism of potentiation of apoptosis by Bcl-2 is relate d to the enhanced reducing potential of bcl-2-overexpressing PC12 cells. (C ) 1999 Elsevier Science B.V. All rights reserved.