Deletion of Herpud1 Enhances Heme Oxygenase-1 Expression in a Mouse Model of Parkinson's Disease

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. © 2016 thuong manh le et al.