Bax accelerates staurosporine-induced but suppresses nigericin-induced neuronal cell death.
Bax, a member of the Bcl-2 multigene family, is known to promote apoptosis. To investigate the role of Bax in an experimentally induced cell death of the murine dopaminergic neuronal cell line (MN9D), we established MN9D cells stably over-expressing murine Bax (MN9D/ Bax) or vector alone (MN9D/Neo). In MN9D/Neo cells treated with either 1 microM staurosporine or 0.1 microM nigericin, a ladder pattern of DNA fragmentation was induced. As expected, over-expression of Bax in MN9D cells accelerated staurosporine-induced cell death as measured by the MTT reduction assay (62.3% survival in MN9D/Neo vs 27.0% survival in MN9D/Bax). Surprizingly, both nigericin-induced cell death and its accompanying DNA fragmentation were largely attenuated in MN9D/Bax cells (22.0% survival in MN9D/Neo vs 86.7% survival in MN9D/Bax). Similar patterns were observed in two other MN9D/Bax cell lines. Cleavage of poly(ADP-ribose)polymerase caused by nigericin was greatly attenuated in MN9D/Bax cells suggesting that, like Bcl-2, Bax suppresses nigericin-induced cell death by inhibiting the activation of cysteine proteases. Thus, our data imply that Bax acts as a negative or positive regulator of cell death depending on the type of death stimulus applied to the cell.
Oh
J H
JH
Department of Biology, Yonsei University College of Science, Seoul, Korea.
O'Malley
K L
KL
Krajewski
S
S
Reed
J C
JC
Oh
Y J
YJ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D053938:DNA Fragmentation; D015870:Gene Expression / Q000187:drug effects; D019254:Genes, bcl-2 / Q000235:genetics*; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D009550:Nigericin / Q000633:toxicity*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019311:Staurosporine / Q000633:toxicity*
D000900:Anti-Bacterial Agents; D011065:Poly(ADP-ribose) Polymerases; D019311:Staurosporine; D009550:Nigericin