ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract: To assess the role of Bcl-XL and its splicederivative, Bcl-Xs, in staurosporine-induced cell death, we used adopaminergic cell line, MN9D, transfected with bcl-xL(MN9D/Bcl-XL), bcl-xs (MN9D/Bcl-Xs),or control vector (MN9D/Neo). Only 8.6% of MN9D/Neo cells survived after 24 hof 1 μM staurosporine treatment. Caspase activity was implicatedbecause a caspase inhibitor,N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (Z-VAD-fmk),attenuated staurosporine-induced cell death. Bcl-XL rescued MN9Dcells from death (89.4% viable cells), whereas Bcl-Xs had little orno effect. Bcl-XL prevented morphologically apoptotic changes aswell as cleavage of poly(ADP-ribose)polymerase (PARP) induced bystaurosporine. It is interesting that a small Bax-immunoreactive proteinappeared 4-8 h after PARP cleavage in MN9D/Neo cells. The appearance of thesmall Bax-immunoreactive protein, however, may be cell type-specific as it wasnot observed in PC12 cells after staurosporine treatment. The sequentialcleavage of PARP and the appearance of the small Bax-immunoreactive protein inMN9D cells were blocked either by Z-VAD-fmk or by Bcl-XL. Thus, ourpresent study suggests that Bcl-XL but not Bcl-Xs 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.1999.0722456.x
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