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

Seongmi Lee, Seung Tack Oh, Ha Jin Jeong, Sok Cheon Pak, Hi Joon Park, Jongpil Kim, Hyun Seok Cho, Songhee Jeon

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Abstract

Familial Parkinson's disease (PD) has been linked to point mutations and duplication of the a-synuclein (a-syn) gene. Mutant a-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 a-synuclein (a-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 a-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 a-syn Tg mice. In the challenging beam test, the hemi and homo a-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 a-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 a-syn Tg mice. Moreover, A53T a-syn overexpression decreased DJ-1 expression in SH-SY5Y cells. These findings suggest that the vulnerability to oxidative injury such as MPTP of A53T a-syn mice can be explained by downregulation of DJ-1.

Original languageEnglish
Pages (from-to)625-632
Number of pages8
JournalKorean Journal of Physiology and Pharmacology
Volume21
Issue number6
DOIs
Publication statusPublished - Nov 2017

Fingerprint

Synucleins
Dopaminergic Neurons
Down-Regulation
Poisons
Parkinson Disease
4-phenyl-1,2,3,6-tetrahydropyridine
Ubiquitin-Conjugating Enzymes
Neurons
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Tyrosine 3-Monooxygenase
Ubiquitin
Point Mutation
Adhesives
Transgenic Mice

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Lee, Seongmi ; Oh, Seung Tack ; Jeong, Ha Jin ; Pak, Sok Cheon ; Park, Hi Joon ; Kim, Jongpil ; Cho, Hyun Seok ; Jeon, Songhee. / MPTP-induced vulnerability of dopamine neurons in A53T a-synuclein overexpressed mice with the potential involvement of DJ-1 downregulation. In: Korean Journal of Physiology and Pharmacology. 2017 ; Vol. 21, No. 6. pp. 625-632.
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abstract = "Familial Parkinson's disease (PD) has been linked to point mutations and duplication of the a-synuclein (a-syn) gene. Mutant a-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 a-synuclein (a-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 a-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 a-syn Tg mice. In the challenging beam test, the hemi and homo a-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 a-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 a-syn Tg mice. Moreover, A53T a-syn overexpression decreased DJ-1 expression in SH-SY5Y cells. These findings suggest that the vulnerability to oxidative injury such as MPTP of A53T a-syn mice can be explained by downregulation of DJ-1.",
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MPTP-induced vulnerability of dopamine neurons in A53T a-synuclein overexpressed mice with the potential involvement of DJ-1 downregulation. / Lee, Seongmi; Oh, Seung Tack; Jeong, Ha Jin; Pak, Sok Cheon; Park, Hi Joon; Kim, Jongpil; Cho, Hyun Seok; Jeon, Songhee.

In: Korean Journal of Physiology and Pharmacology, Vol. 21, No. 6, 11.2017, p. 625-632.

Research output: Contribution to journalArticle

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AU - Lee, Seongmi

AU - Oh, Seung Tack

AU - Jeong, Ha Jin

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AU - Park, Hi Joon

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