title: Deletion of Herpud1 Enhances Heme Oxygenase-1 Expression in a Mouse Model of Parkinson's Disease.
abstract: Herp is an endoplasmic reticulum- (ER-) resident membrane protein that plays a role in ER-associated degradation. We studied the expression of Herp and its effect on neurodegeneration in a mouse model of Parkinson's disease (PD), in which both the oxidative stress and the ER stress are evoked. Eight hours after administering a PD-related neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), to mice, the expression of Herp increased at both the mRNA and the protein levels. Experiments using Herpud1 (+/+) and Herpud1 (-/-) mice revealed that the status of acute degeneration of nigrostriatal neurons and reactive astrogliosis was comparable between two genotypes after MPTP injection. However, the expression of a potent antioxidant, heme oxygenase-1 (HO-1), was detected to a higher degree in the astrocytes of Herpud1 (-/-) mice than in the astrocytes of Herpud1 (+/+) mice 24 h after MPTP administration. Further experiments using cultured astrocytes revealed that the stress response against MPP(+), an active form of MPTP, and hydrogen peroxide, both of which cause oxidative stress, was comparable between the two genotypes. These results suggest that deletion of Herpud1 may cause a slightly higher level of initial damage in the nigrastrial neurons after MPTP administration but is compensated for by higher induction of antioxidants such as HO-1 in astrocytes.
authors.affiliation: Department of Neuroanatomy, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Thuong Manh
authors.initials: TM
authors.lastname: Le
authors.affiliation: Department of Neuroanatomy, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Hashida
authors.affiliation: Department of Neuroanatomy, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Hieu Minh
authors.initials: HM
authors.lastname: Ta
authors.affiliation: Department of Neuroanatomy, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8640, Japan; CREST, JST (Japan Science and Technology), Tokyo 102-8666, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Takarada-Iemata
authors.affiliation: Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center, Osaka 565-8565, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kokame
authors.affiliation: Department of Neuroanatomy, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8640, Japan; CREST, JST (Japan Science and Technology), Tokyo 102-8666, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Kitao
authors.affiliation: Department of Neuroanatomy, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8640, Japan; CREST, JST (Japan Science and Technology), Tokyo 102-8666, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Hori