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 responsible 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 apoptosis final common pathway). We now report that overexpression of bcl-2 in PC12 cells does not protect the cells from NCS-induced oxidation of membrane phosphatidylserine (PS), and results in potentiation of NCS-induced externalization of membrane PS, two events associated with the apoptosis final common pathway. The mechanism of potentiation of apoptosis by Bcl-2 is related to the enhanced reducing potential of bcl-2-overexpressing PC12 cells.
Schor
N F
NF
Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA. nfschor@vms.cis.pitt.edu
Tyurina
Y Y
YY
Fabisiak
J P
JP
Tyurin
V A
VA
Lazo
J S
JS
Kagan
V E
VE
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D019254:Genes, bcl-2; D015227:Lipid Peroxidation / Q000502:physiology*; D008566:Membranes / Q000378:metabolism; D010084:Oxidation-Reduction; D016716:PC12 Cells; D010718:Phosphatidylserines / Q000378:metabolism*; D051381:Rats; D014162:Transfection; D009353:Zinostatin / Q000494:pharmacology
D010718:Phosphatidylserines; D009353:Zinostatin