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http://dx.doi.org/10.4196/kjpp.2017.21.6.625

MPTP-induced vulnerability of dopamine neurons in A53T α-synuclein overexpressed mice with the potential involvement of DJ-1 downregulation  

Lee, Seongmi (Department of Biomedical Engineering, Dongguk University)
Oh, Seung Tack (Research Institute, Dongkwang Pharmaceutical Company, Ltd.)
Jeong, Ha Jin (Department of Biomedical Sciences, Center for Creative Biomedical Scientists at Chonnam National University)
Pak, Sok Cheon (School of Biomedical Sciences, Charles Sturt University)
Park, Hi-Joon (Department of Korean Medical Science, Graduate School of Korean Medicine, Kyung Hee University)
Kim, Jongpil (Department of Biomedical Engineering, Dongguk University)
Cho, Hyun-seok (Department of Acupuncture and Moxibustion, Dongguk University of Korea Medicine, Dongguk University Bundang Korean Medical Hospital)
Jeon, Songhee (Department of Biomedical Sciences, Center for Creative Biomedical Scientists at Chonnam National University)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.21, no.6, 2017 , pp. 625-632 More about this Journal
Abstract
Familial Parkinson's disease (PD) has been linked to point mutations and duplication of the ${\alpha}$-synuclein (${\alpha}$-syn) gene. Mutant ${\alpha}$-syn expression increases the vulnerability of neurons to exogenous insults. In this study, we developed a new PD model in the transgenic mice expressing mutant hemizygous (hemi) or homozygous (homo) A53T ${\alpha}$-synuclein (${\alpha}$-syn Tg) and their wildtype (WT) littermates by treatment with sub-toxic (10 mg/kg, i.p., daily for 5 days) or toxic (30 mg/kg, i.p., daily for 5 days) dose of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Tyrosine hydroxylase and Bcl-2 levels were reduced in the ${\alpha}$-syn Tg but not WT mice by sub-toxic MPTP injection. In the adhesive removal test, time to remove paper was significantly increased only in the homo ${\alpha}$-syn Tg mice. In the challenging beam test, the hemi and homo ${\alpha}$-syn Tg mice spent significantly longer time to traverse as compared to that of WT group. In order to find out responsible proteins related with vulnerability of mutant ${\alpha}$-syn expressed neurons, DJ-1 and ubiquitin enzyme expressions were examined. In the SN, DJ-1 and ubiquitin conjugating enzyme, UBE2N, levels were significantly decreased in the ${\alpha}$-syn Tg mice. Moreover, A53T ${\alpha}$-syn overexpression decreased DJ-1 expression in SH-SY5Y cells. These findings suggest that the vulnerability to oxidative injury such as MPTP of A53T ${\alpha}$-syn mice can be explained by downregulation of DJ-1.
Keywords
Apoptosis; DJ-1; MPTP; Parkinson's disease; Synuclein;
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