Functional analysis of DJ-1, a causative gene product for familial Parkinson's disease

• Project/Area Number: 17590049
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: University of Yamanashi
• Principal Investigator: TAIRA Takahiro University of Yamanashi, Interdisciplinary Graduate School of Medicine and Engineering, Professor, 大学院医学工学総合研究部, 教授 (70197036)
• Project Period (FY): 2005 – 2006
• Project Status: Completed (Fiscal Year 2006)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000); Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
• Keywords: DJ-1 / Parkinson's disease / Oxidative stress / reactive oxygen species / 病態モデル / 神経変成疾患 / 病態モデル動物

Research Abstract

DJ-1 has recently been shown to be responsible for onset of familial Parkinson's disease (PD), PARK7. DJ-1 has been shown to play roles in transcriptional regulation and anti-oxidative stress, and loss of its function is thought to trigger onset of PD. In this study, a recombinant DJ-1 protein was administrated into the brain of PD model rats that had been injected to 6-hydroxydopamine (6-OHDA) in the left substantia nigra. PD phenotypes, including dopaminergic neuron death both in the substantia nigra and striatum, decrease in dopamine and dopamine transporter levels in the striatum, and motor abnormality, were dramatically improved by wild-type DJ-1 but not L166P DJ-1, a mutant form of DJ-1 found in PD patients. Furthermore, production of reactive oxygen species and cell death induced by 6-OHDA in SH-SY5Y cells were inhibited by addition of the recombinant DJ-1. These findings suggest that DJ-1 is a therapeutic target for PD.

Research Products

• [Journal Article] DJ-1 degrades transthyretin and inactive form of DJ-1 is secreted in familial amyloidotic polyneuropathy. (2007)
  • Author(s): Koide-Yoshida, S., et al.
  • Journal Title: Int. J. Molc. Med. 19 Pages: 885-893
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Neurodegenecation of mouse nigrostriatal dopaminergic system induced by repeated oral administration of rotenone is preventel by 4-phenylbutyrate, a chemical chaperone. (2007)
  • Author(s): Inden, M., et al.
  • Journal Title: J. Neurochem. (In press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] DJ-1 degrades transthyretin and an inactive form of DJ-1 is secreted in familial amyloidotic polyneuropathy. (2007)
  • Author(s): Koide-Yoshida, S., Niki, T., Ueda, M., Himeno, S., Taira, T., Iguchi-Ariga, S.M.M., Ando, Y., Ariga, H.
  • Journal Title: Int. J. Mol. Med. 19 Pages: 885-893
  • NAID: 120005350114
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Neurodegeneration of mouse nigrostriatal dopaminergic system induced by repeated oral administration of rotenone is prevented by 4-phenylbutyrate, a chemical chaperone. (2007)
  • Author(s): Inden, M., Kitamura, Y., Takeuchi, H., Yanagida, T., Takata, K., Kobayashi, Y., Taniguchi, T., Yoshimoto, K., Kaneko, M., Okuma, Y., Taira, T., Ariga, H., Shimohama, S.
  • Journal Title: J. Neurochem. (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Proper SUMO-1 conjugation is essential to DJ-1 to exert its full activities. (2006)
  • Author(s): Shinbo, Y., et al.
  • Journal Title: Cell Death. Differ. 13 Pages: 96-108
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Induction of reactive oxygen species by bisphenol A and abrogation of bisphenol A-induced cell injury by DJ-1 (2006)
  • Author(s): Ooe, H., et al.
  • Journal Title: Toxicol. Sci. 88 Pages: 114-126
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Distinct localizations and repression activities of MM-1 isoforms toward c-Myc. (2006)
  • Author(s): Hagio, Y., et al.
  • Journal Title: J. Cell. Biochem. 97 Pages: 145-155
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Association of DJ-1 with chaperones and enhanced association and colocalozation with mitochondorial HSP70 by oxidative stress. (2006)
  • Author(s): Li, HM., et al.
  • Journal Title: Free Radic. Res. 39 Pages: 1091-1099
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] DJ-1 interacts with HIPK1 and affects H202-inducede cell death (2006)
  • Author(s): Sekito, A., et al.
  • Journal Title: Free Radic. Res. 40 Pages: 155-165
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] PARK7 DJ-1 protects against degeneration of nigral dopaminergic neurons in Parkinson' s disease rat model. (2006)
  • Author(s): Inden, M., et al.
  • Journal Title: Neurobiol. Dis. 24 Pages: 144-158
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Protection against nonylphenol-induced cell death by DJ-1 in cultured Japanese medaka(Oryzias latipes) cell. (2006)
  • Author(s): Li, HM., et al.
  • Journal Title: Toxicology 228 Pages: 229-238
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Distribution of DJ-1, Parkinson's disease-related protein PARK7, and its alteration in 6-hydoroxydopamine-treated hemiparkinsonian rat brain. (2006)
  • Author(s): Yanagida, T., et al.
  • Journal Title: J. Pharmacol. Sci. 102 Pages: 243-247
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Distribution of DJ-1, Parkinson's disease-related protein PARK7, and its alteration in 6-hydroxydopamine-treated hemiparkinsonian rat brain. (2006)
  • Author(s): Yanagida, T., Takada, K., Inden, M., Kitamura, Y., Taniguchi, T., Yoshimoto, K., Taira, T., Ariga, H.
  • Journal Title: J. Pharmacol. Sci. 102 Pages: 243-247
  • NAID: 10020345801
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Protection against nonylphenol-induced cell death by DJ-1 in cultured Japanese medaka (Oryzias latipes) cells (2006)
  • Author(s): Li, H.M., Taira, T., Maita, C., Ariga, H., Iguchi-Ariga, S.M.M.
  • Journal Title: Toxicology 228 Pages: 229-238
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] PARK7 DJ-1 protects against degeneration of nigral dopaminergic neurons in Parkinson's disease rat model. (2006)
  • Author(s): Inden, M., Taira, T., Kitamura, Y., Yanagida, T., Tsuchiya, D., Takata, K., Yanagisawa, D., Nishimura, K., Taniguchi, T., Kiso, Y., Yoshimoto, Y., Wagatsuma, T., Koide-Yoshida, S., Iguchi-Ariga, S.M.M., Shimohama, S., Ariga, H.
  • Journal Title: Neurobiol. Dis. 24 Pages: 144-158
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] DJ-1 interacts with HIPK1 and affects H202-induced cell death. (2006)
  • Author(s): Sekito, A., Koide-Yoshida, S., Niki, T., Taira, T., Iguchi-Ariga, S.M.M., Ariga, H.
  • Journal Title: Free Radic. Res. 40 Pages: 155-165
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Distinct Localizations and Repression Activities of MM-1 Isoforms toward c-Myc (2006)
  • Author(s): Hagio, Y., Kimura, Y., Taira, T., Fujioka, Y., Iguchi-Ariga, S.M.M., Ariga, H.
  • Journal Title: J. Cell. Biochem. 97 Pages: 145-155
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Proper SUMO-1 conjugation is essential to DJ-1 to exert its full activities. (2006)
  • Author(s): Shinbo, Y., Niki, T., Taira, T., Ooe, H., Takahashi-Niki, K., Maita, C Seino, C., Iguchi-Ariga, S.M.M., Ariga, H.
  • Journal Title: Cell Death Diff. 13 Pages: 96-108
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Proper SUMO-1 conjugation is essential to DJ-1 to exert its full activities. (2006)
  • Author(s): Shinbo, Y.
  • Journal Title: Cell Death and Differentiation 13 Pages: 96-108
• [Journal Article] Distinct Localizations and Repression Activities of MM-1 Isoforms toward c-Myc (2006)
  • Author(s): Hagio, Y.
  • Journal Title: J.Cell.Biochem 97 Pages: 145-155
• [Journal Article] PARK7 DJ-1 protects against degeneration of nigral dopaminergic neurons in Parkinson's disease rat model. (2006)
  • Author(s): Inden, M.
  • Journal Title: Neurobiol.Dis 24 Pages: 144-158
• [Journal Article] Protection against nonylphenol-induced cell death by DJ-1 in cultured Japanese medaka (Oryzias latipes) cells. (2006)
  • Author(s): Li, H.M.
  • Journal Title: Toxicology 228 Pages: 229-238
• [Journal Article] Distribution of DJ-1, Parkinson's disease-related protein PARK7, and its alteration in 6-hydroxydopamine-treated hemiparkinsonian rat brain. (2006)
  • Author(s): Yanagida, T.
  • Journal Title: Pharmacol.Sci 102 Pages: 243-247
• [Journal Article] Parkinson病原因遺伝子PARK7とDJ-1遺伝子の機能 (2006)
  • Author(s): 有賀寛芳
  • Journal Title: 神経内科 65 Pages: 135-139
• [Journal Article] DJ-1 restores p53 transcription activity by Topors/p53BP3 (2005)
  • Author(s): Shinbo, Y., et al.
  • Journal Title: Int J Oncl. 26 Pages: 641-648
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Stimulation of transforming activity of DJ-1 by Abstract, a DJ-1-binding protein. (2005)
  • Author(s): Sekito, A., et al.
  • Journal Title: Int J Oncl. 26 Pages: 685-689
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Structure and characterization of AAT-1 isoforms. (2005)
  • Author(s): Matsuda, E., et al.
  • Journal Title: Biol. Pharm. Bull. 28 Pages: 898-901
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Expression profiles of genes in DJ-1-knockdown and L166P DJ-1 mutan cells (2005)
  • Author(s): Nishinaga, H., et al.
  • Journal Title: Neurosci. Lett. 16:390 Pages: 54-59
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Association of DJ-1 with chaperones and enhanced association and colocalization with mitochondrial Hsp70 by oxidative stress. (2005)
  • Author(s): Li, H.M., Niki, T., Taira, T., Iguchi-Ariga, S.M.M., Ariga, H.
  • Journal Title: Free Radic. Res. 39 Pages: 1091-1099
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Expression profiles of genes in DJ-1-knockdown and L166P DJ-1 mutant cells. (2005)
  • Author(s): Nishinaga, H., Takahashi-Niki, K., Taira, T., Andreadis, A., Iguchi-Ariga, S.M.M., Ariga, H.
  • Journal Title: Neuroscience Lett. 390 Pages: 54-59
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Induction of reactive oxygen species by bisphenol A and abrogation of bisphenol A-induced cell injury by DJ-1. (2005)
  • Author(s): Ooe, H., Taira, T., Iguchi-Ariga, S.M.M., Ariga, H.
  • Journal Title: Toxicol. Sci. 88 Pages: 114-126
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Structure and characterization of AAT-1 isoforms (2005)
  • Author(s): Matsuda, E., Ishizaki, R., Taira, T., Iguchi-Ariga, S.M.M., Ariga, H.
  • Journal Title: Biol. Pharm. Bull. 28 Pages: 898-901
  • NAID: 120005350119
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Stimulation of transforming activity of DJ-1 by Abstrakt, a DJ-1-binding protein. (2005)
  • Author(s): Sekito A., Taira, T., Niki, T., Iguchi-Ariga, S.M.M., Ariga, H.
  • Journal Title: Int. J. Oncol. 26 Pages: 685-689
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] DJ-1 restores p53 transcription activity inhibited by Topors/p53BP3. (2005)
  • Author(s): Shinbo, Y., Taira, T., Niki, T., Iguchi-Ariga, S.M.M., Ariga, H.
  • Journal Title: Int. J. Oncol. 26 Pages: 641-648
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Stimulation of transforming activity of DJ-1 by Abstrakt, a DJ-1-binding protein. (2005)
  • Author(s): Shinbo, Y., Taira, T., Niki, T., Iguchi-Ariga, S.M.M., Ariga, H.
  • Journal Title: Int.J.Oncol. 26 Pages: 685-689
• [Journal Article] DJ-1 restores p53 transcription activity inhibited by Topors/p53BP3 (2005)
  • Author(s): Sekito A., Taira, T., Niki, T., Iguchi-Ariga, S.M.M., Ariga, H
  • Journal Title: Int.J.Oncol. 26 Pages: 641-648
• [Journal Article] Structure and characterization of AAT-1 isoforms (2005)
  • Author(s): Matsuda, E., Ishizaki, R., Taira, T., Iguchi-Ariga, S.M.M., Ariga, H.
  • Journal Title: Biol.Pharm.Bull. 28 Pages: 898-901
  • NAID: 120005350119
• [Journal Article] Association of DJ-1 with chaperones and enhanced association and colocalization with mitochondrial Hsp70 by oxidative stress (2005)
  • Author(s): Li, H.M., Niki, T., Taira T., Iguchi-Ariga, S.M.M., Ariga, H.
  • Journal Title: Free Radic.Res. 39 Pages: 1091-1099
• [Journal Article] Induction of reactive oxygen species by bisphenol A and abrogation of bisphenol A-induced cell injury by DJ-1. (2005)
  • Author(s): Ooe, H., Taira, T., Iguchi-Ariga, S.M.M., Ariga, H
  • Journal Title: Toxicol.Sci. 88 Pages: 114-126