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Sequential cleavage of poly(ADP-ribose)polymerase and appearance of a small Bax-immunoreactive protein are blocked by Bcl-X(L) and caspase inhibitors during staurosporine-induced dopaminergic neuronal apoptosis.

Kim, JE; Oh, JH; Choi, WS; Chang, II; Sohn, S; Krajewski, S; Reed, JC; O'Malley, KL; Oh, YJ
Journal of neurochemistry, 72(6):2456-2463, 1999
Journal Title
Journal of neurochemistry
To assess the role of Bcl-X(L) and its splice derivative, Bcl-X(S), in staurosporine-induced cell death, we used a dopaminergic cell line, MN9D, transfected with bcl-xL (MN9D/Bcl-X(L)), bcl-xS (MN9D/Bcl-X(S)), or control vector (MN9D/Neo). Only 8.6% of MN9D/Neo cells survived after 24 h of 1 microM staurosporine treatment. Caspase activity was implicated because a caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (Z-VAD-fmk), attenuated staurosporine-induced cell death. Bcl-X(L) rescued MN9D cells from death (89.4% viable cells), whereas Bcl-X(S) had little or no effect. Bcl-X(L) prevented morphologically apoptotic changes as well as cleavage of poly(ADP-ribose)polymerase (PARP) induced by staurosporine. It is interesting that a small Bax-immunoreactive protein appeared 4-8 h after PARP cleavage in MN9D/Neo cells. The appearance of the small Bax-immunoreactive protein, however, may be cell type-specific as it was not observed in PC12 cells after staurosporine treatment. The sequential cleavage of PARP and the appearance of the small Bax-immunoreactive protein in MN9D cells were blocked either by Z-VAD-fmk or by Bcl-X(L). Thus, our present study suggests that Bcl-X(L) but not Bcl-X(S) prevents staurosporine-induced apoptosis by inhibiting the caspase activation that may be directly or indirectly responsible for the appearance of the small Bax-immunoreactive protein in some types of neurons.
MeSH terms
AnimalsApoptosis/drug effectsApoptosis/physiology*Caspases/antagonists & inhibitors*Cell LineCycloheximide/pharmacologyDopamine/metabolism*KineticsMiceNeurons/cytologyNeurons/drug effectsNeurons/metabolism*Poly(ADP-ribose) Polymerases/metabolism*Proto-Oncogene Proteins/metabolism*Proto-Oncogene Proteins c-bcl-2/biosynthesisProto-Oncogene Proteins c-bcl-2/geneticsProto-Oncogene Proteins c-bcl-2/metabolism*Recombinant Proteins/biosynthesisRecombinant Proteins/metabolismStaurosporine/pharmacology*Transfectionbcl-2-Associated X Proteinbcl-X Protein
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Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
AJOU Authors
손, 성향
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