0 230

Cited 0 times in

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.

Authors
Kim, JE; Oh, JH; Choi, WS; Chang, II; Sohn, S; Krajewski, S; Reed, JC; O'Malley, KL; Oh, YJ
Citation
Journal of neurochemistry, 72(6):2456-2463, 1999
Journal Title
Journal of neurochemistry
ISSN
0022-30421471-4159
Abstract
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
PMID
10349855
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
AJOU Authors
손, 성향
Full Text Link
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse