Prion protein protects against ethanol-induced Bax-mediated cell death in vivo.
Prion protein inhibits Bax activation and Bax-mediated cell death in primary cultures of human neurons and in MCF-7 cells. To determine whether prion protein can protect against Bax-mediated cell death in vivo, wild-type, null and prion over-expressing mice were subjected to Bax-dependent ethanol induced neuronal apoptotic cell death and the brains were immunostained for active caspase-3 as a downstream marker of Bax activation. Bax activation occurs in all ethanol-injected mice independent of their genotype. A higher level of cell death is present in ethanol-injected null mice than in wild-type and prion over-expressing mice. We conclude that prion protein protects some, but not all neurons, against Bax-mediated cell death in this experimental paradigm.
Gains
Malcolm J
MJ
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
Roth
Kevin A
KA
LeBlanc
Andrea C
AC
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D006224:Cricetinae; D004789:Enzyme Activation; D000431:Ethanol / Q000494:pharmacology*; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects*; D011328:Prions / Q000235:genetics / Q000502:physiology*; D013057:Spectrum Analysis / Q000379:methods; D051028:bcl-2-Associated X Protein / Q000502:physiology*
D002492:Central Nervous System Depressants; D011328:Prions; D051028:bcl-2-Associated X Protein; D000431:Ethanol; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases