NR AMRT
AU Wong,B.S.; Liu,T.; Paisley,D.; Li,R.; Pan,T.; Chen,S.G.; Perry,G.; Petersen,R.B.; Smith,M.A.; Melton,D.W.; Gambetti,P.; Brown,D.R.; Sy,M.S.
TI Induction of HO-1 and NOS in doppel-expressing mice devoid of PrP: implications for doppel function.
QU Molecular and Cellular Neurosciences 2001 Apr; 17(4): 768-75
PT journal article
AB Ectopic expression of the doppel (Dpl) protein, a homologue of the prion protein (PrP), was recently associated with cerebellar Purkinje cell degeneration observed in two aging prion protein knock-out (Prnp(0/0)) mouse lines. We investigated the possible role of Dpl in oxidative metabolism. Two Prnp(0/0) mouse lines of similar genetic background were studied. One line expresses Dpl in the brain and displays Dpl-associated cerebellar abnormalities. The other has no elevated expression of Dpl and no cerebellar abnormalities. We observed a correlation between Dpl expression and the induction of both heme oxygenase 1 (HO-1) and nitric oxide synthase systems (nNOS and iNOS). These responses are suggestive of increased oxidative stress in the brains of the Dpl-expressing Prnp(0/0) mice. No induction was observed with Hsp-60, indicating a specific response by the HO/NOS system. We proposed that Dpl expression exacerbates oxidative damage that is antagonistic to the protective function of wild-type PrP.
MH Animal; Chaperonin 60/genetics; Gene Expression Regulation, Enzymologic; Heme Oxygenase (Decyclizing)/*genetics; Lipid Peroxidation/physiology; Mice; Mice, Knockout; Nitric-Oxide Synthase/*genetics; Nitrites/metabolism; Oxidative Stress/physiology; Prions/*genetics/*metabolism; Purkinje Cells/*enzymology; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
AD Institute of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio
SP englisch
PO USA