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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

 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 
 Journal of Neurochemistry, Vol.72(6) : 2456-2463, 1999 
Journal Title
 Journal of Neurochemistry 
Issue Date
Animals ; Apoptosis/drug effects ; Apoptosis/physiology* ; Caspase Inhibitors* ; Cell Line ; Cycloheximide/pharmacology ; Dopamine/metabolism* ; Kinetics ; Mice ; Neurons/cytology ; Neurons/drug effects ; Neurons/metabolism* ; Poly(ADP-ribose) Polymerases/metabolism* ; Proto-Oncogene Proteins/metabolism* ; Proto-Oncogene Proteins c-bcl-2/biosynthesis ; Proto-Oncogene Proteins c-bcl-2/genetics ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Recombinant Proteins/biosynthesis ; Recombinant Proteins/metabolism ; Staurosporine/pharmacology* ; Transfection ; bcl-2-Associated X Protein ; bcl-X Protein
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.
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2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Chang, In Ik(장인익)
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