Up-regulation of hMUTYH, a DNA repair enzyme, in the mitochondria of substantia nigra in Parkinson's disease.

Takeo Arai, Jiro Fukae, Taku Hatano, Shin ichiro Kubo, Toshio Ohtsubo, Yusaku Nakabeppu, Hideo Mori, Yoshikuni Mizuno, Nobutaka Hattori

Research output: Contribution to journalArticle

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Abstract

There is ample evidence for the involvement of oxidative stress in mitochondrial DNA damage and repair mechanisms in Parkinson's disease (PD). The human MutY homolog (hMUTYH) which removes misincorporated adenine opposite 8-oxoG in DNA functions in post-replication, and is localized in the nuclei and mitochondria. We hypothesized that hMUTYH is involved in the disease process of PD. To test our hypothesis, we performed immunohistochemical and biochemical studies on brains of patients with PD and those of control patients. Our results showed up-regulation of hMUTYH in the mitochondria of the SN of PD patients. Western blot analysis also revealed high hMUTYH levels in PD patients and expression of a 47-kDa molecule in the brains as the major isoform. This molecule was localized within the mitochondria as confirmed by double staining with a mitochondrial marker. To confirm the presence of this molecule, we examined the mRNAs of isoforms that translate to the 47-kDa molecule. Based on the amount of mRNAs, the major molecule was alpha4. Interestingly, this molecule lacks the mitochondria targeting sequence. Our results suggest that hMUTYH might be a useful marker of oxidative stress and that oxidative stress and genomic instability are important in the PD disease process.

Original languageEnglish
Pages (from-to)139-145
Number of pages7
JournalActa neuropathologica
Volume112
Issue number2
DOIs
Publication statusPublished - Jan 1 2006

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DNA Repair Enzymes
Substantia Nigra
Parkinson Disease
Mitochondria
Up-Regulation
Oxidative Stress
RNA Isoforms
Genomic Instability
Brain
Adenine
Mitochondrial DNA
DNA Repair
DNA Damage
Protein Isoforms
Western Blotting
Staining and Labeling
Messenger RNA
DNA

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Up-regulation of hMUTYH, a DNA repair enzyme, in the mitochondria of substantia nigra in Parkinson's disease. / Arai, Takeo; Fukae, Jiro; Hatano, Taku; Kubo, Shin ichiro; Ohtsubo, Toshio; Nakabeppu, Yusaku; Mori, Hideo; Mizuno, Yoshikuni; Hattori, Nobutaka.

In: Acta neuropathologica, Vol. 112, No. 2, 01.01.2006, p. 139-145.

Research output: Contribution to journalArticle

Arai, T, Fukae, J, Hatano, T, Kubo, SI, Ohtsubo, T, Nakabeppu, Y, Mori, H, Mizuno, Y & Hattori, N 2006, 'Up-regulation of hMUTYH, a DNA repair enzyme, in the mitochondria of substantia nigra in Parkinson's disease.', Acta neuropathologica, vol. 112, no. 2, pp. 139-145. https://doi.org/10.1007/s00401-006-0081-9
Arai, Takeo ; Fukae, Jiro ; Hatano, Taku ; Kubo, Shin ichiro ; Ohtsubo, Toshio ; Nakabeppu, Yusaku ; Mori, Hideo ; Mizuno, Yoshikuni ; Hattori, Nobutaka. / Up-regulation of hMUTYH, a DNA repair enzyme, in the mitochondria of substantia nigra in Parkinson's disease. In: Acta neuropathologica. 2006 ; Vol. 112, No. 2. pp. 139-145.
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