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

Boon Seng Wong; Tong Liu; Derek Paisley; Ruliang Li; Tao Pan; Shu G. Chen; George Perry; Robert B. Petersen; Mark A. Smith; David W. Melton; Pierluigi Gambetti; David R. Brown; Man Sun Sy

doi:10.1006/mcne.2001.0963

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

Boon Seng Wong, Tong Liu, Derek Paisley, Ruliang Li, Tao Pan, Shu G. Chen, George Perry, Robert B. Petersen, Mark A. Smith, David W. Melton, Pierluigi Gambetti, David R. Brown, Man Sun Sy

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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.

Original language	English
Pages (from-to)	768-775
Number of pages	8
Journal	Molecular and Cellular Neuroscience
Volume	17
Issue number	4
DOIs	https://doi.org/10.1006/mcne.2001.0963
State	Published - 2001

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@article{9b90b3629ad54176a0c94d68efaeeaa3,

title = "Induction of HO-1 and NOS in doppel-expressing mice devoid of PrP: Implications for doppel function",

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 (Prnp0/0) mouse lines. We investigated the possible role of Dpl in oxidative metabolism. Two Prnp0/0 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 Prnp0/0 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.",

author = "Wong, {Boon Seng} and Tong Liu and Derek Paisley and Ruliang Li and Tao Pan and Chen, {Shu G.} and George Perry and Petersen, {Robert B.} and Smith, {Mark A.} and Melton, {David W.} and Pierluigi Gambetti and Brown, {David R.} and Sy, {Man Sun}",

note = "Funding Information: The authors thank Jean Manson (Institute for Animal Health) for Npu Prnp0/0 mice and David Westaway for pCDNA construct containing Doppel cDNA. DRB was supported by a fellowship from BBSRC (UK). This work was supported in part by grants from the National Institutes of Health (AG14359 to P.G.; NS38648 to M.A.S. and G.P.), the Britton Fund (to P.G.), MRC UK (G9818420 to D.W.M.), BBSRC (8/BS410551 to D.R.B.) and the EU Biomed Commission (976051 to D.R.B.).",

year = "2001",

doi = "10.1006/mcne.2001.0963",

language = "English",

volume = "17",

pages = "768--775",

journal = "Molecular and Cellular Neuroscience",

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T1 - Induction of HO-1 and NOS in doppel-expressing mice devoid of PrP

T2 - Implications for doppel function

AU - Wong, Boon Seng

AU - Liu, Tong

AU - Paisley, Derek

AU - Li, Ruliang

AU - Pan, Tao

AU - Chen, Shu G.

AU - Perry, George

AU - Petersen, Robert B.

AU - Smith, Mark A.

AU - Melton, David W.

AU - Gambetti, Pierluigi

AU - Brown, David R.

AU - Sy, Man Sun

N1 - Funding Information: The authors thank Jean Manson (Institute for Animal Health) for Npu Prnp0/0 mice and David Westaway for pCDNA construct containing Doppel cDNA. DRB was supported by a fellowship from BBSRC (UK). This work was supported in part by grants from the National Institutes of Health (AG14359 to P.G.; NS38648 to M.A.S. and G.P.), the Britton Fund (to P.G.), MRC UK (G9818420 to D.W.M.), BBSRC (8/BS410551 to D.R.B.) and the EU Biomed Commission (976051 to D.R.B.).

PY - 2001

Y1 - 2001

N2 - 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 (Prnp0/0) mouse lines. We investigated the possible role of Dpl in oxidative metabolism. Two Prnp0/0 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 Prnp0/0 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.

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 (Prnp0/0) mouse lines. We investigated the possible role of Dpl in oxidative metabolism. Two Prnp0/0 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 Prnp0/0 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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DO - 10.1006/mcne.2001.0963

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AN - SCOPUS:0035025086

SN - 1044-7431

VL - 17

SP - 768

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JO - Molecular and Cellular Neuroscience

JF - Molecular and Cellular Neuroscience

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ER -

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

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