NR ASXT
AU Roucou,X.; Giannopoulos,P.N.; Zhang,Y.; Jodoin,J.; Goodyer,C.G.; LeBlanc,A.
TI Cellular prion protein inhibits proapoptotic Bax conformational change in human neurons and in breast carcinoma MCF-7 cells
QU Cell Death and Differentiation 2005 Jul; 12(7): 783-95
PT journal article
AB Prion protein (PrP) prevents Bcl-2-associated protein X (Bax)-mediated cell death, but the step at which PrP inhibits is not known. We first show that PrP is very specific for Bax and cannot prevent Bak (Bcl-2 antagonist killer 1)-, tBid-, staurosporine- or thapsigargin-mediated cell death. As Bax activation involves Bax conformational change, mitochondrial translocation, cytochrome c release and caspase activation, we investigated which of these events was inhibited by PrP. PrP inhibits Bax conformational change, cytochrome c release and cell death in human primary neurons and MCF-7 cells. Serum deprivation-induced Bax conformational change is more rapid in PrP-null cells. PrP does not prevent active caspase-mediated cell death. PrP does not colocalize with Bax in normal or apoptotic primary neurons and cannot prevent Bax-mediated cytochrome c release in a mitochondrial cell-free system. We conclude that PrP protects against Bax-mediated cell death by preventing the Bax proapoptotic conformational change that occurs initially in Bax activation.
MH *Apoptosis/drug effects; Breast Neoplasms/*metabolism/pathology; Carrier Proteins/metabolism; Cell Line, Tumor; Cysteine Endopeptidases/metabolism; Cytochromes c/metabolism; Enzyme Inhibitors/pharmacology; Female; Humans; Membrane Proteins/metabolism; Mitochondria/metabolism; Neurons/drug effects/*metabolism; PrPc Proteins/*metabolism; Protein Structure, Quaternary; Protein Transport/drug effects; Proto-Oncogene Proteins c-bcl-2/antagonists &; inhibitors/*chemistry/*metabolism; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Thapsigargin/pharmacology
AD The Bloomfield Center for Research in Aging, Lady Davis Institute for Medical Research, The Sir Mortimer B Davis Jewish General Hospital, Montreal, Quebec, Canada.
SP englisch
PO England