Induction of HO-1 and NOS in doppel-expressing mice devoid of PrP: implications for doppel function

Molecular and Cellular Neurosciences
B S WongM S Sy

Abstract

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.

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Citations

Mar 25, 2005·Molecular Biology of the Cell·Marisa BriniMaria Catia Sorgato
Jul 3, 2002·The EMBO Journal·Luciana B ChiariniRafael Linden
Jun 19, 2008·Annual Review of Neuroscience·Adriano AguzziJuliane Bremer
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