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

Ji Eun Kim, Jae H. Oh, Won Seok Choi, In I. Chang, Seonghyang Sohn, Stanislaw Krajewski, John C. Reed, Karen L. O'Malley, Young J. Oh

Research output: Contribution to journalArticle

21 Citations (Scopus)

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-X(L) (MN9D/Bcl-X(L)), bcl-x(S) (MN9D/Bcl-X(S)), or control vector (MN9D/Neo). Only 8.6% of MN9D/Neo cells survived after 24 h of 1 μM 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.

Original languageEnglish
Pages (from-to)2456-2463
Number of pages8
JournalJournal of Neurochemistry
Volume72
Issue number6
DOIs
Publication statusPublished - 1999 Jun 3

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

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