Investigation of the mechanism of neuroprotection by neoechinulin A

2011 Fiscal Year Final Research Report

• Project/Area Number: 21580131
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bioproduction chemistry/Bioorganic chemistry
• Research Institution: Tokyo University of Science
• Principal Investigator: WATANABE Nobuo 東京理科大学, 理工学部, 助教 (80396928)
• Co-Investigator(Kenkyū-buntansha): ARAI Takao 東京理科大学, 理工学部・応用生物科学科, 教授 (60107422)
• Co-Investigator(Renkei-kenkyūsha): KURAMOCHI Kouji 京都府立大学, 農学部, 准教授 (90408708) ; KOBAYASHI Susumu 東京理科大学, 薬学部, 教授 (70101102)
• Project Period (FY): 2009 – 2011
• Keywords: 薬理学 / 痴呆 / 老化 / 抗生物質 / 神経科学

Research Abstract

Cytotoxicity by reactive nitrogen species is suggested responsible for various neurodegenerative diseases. Treatment with neoechinulin A renders cells resistant to insults by reactive nitrogen species but the mechanism remained unclear. In this study, we clarified a novel mechanism underlying the cytoprotective action of neoechinulin A treatment ; neoechinulin A engenders an increase in cellular reserve capacity for NAD(P) H generation. We also established for the first time a cellular model of Alzheimer's disease, with which the effectiveness of neoechinulin A would be assessed.

Research Products

• [Journal Article] Prolonged nitric oxide treatment induces tau aggregation in SH-SY5Y cells (2012)
  • Author(s): Takahashi M, Nonaka T, Hasegawa M, Watanabe N, Arai T
  • Journal Title: Neuroscience Letters Volume: 510 Pages: 48-52
• [Journal Article] S-nitrosation of cellular proteins by NO donors in rat embryonic fibroblast 3Y1 cells : factors affecting S-nitrosation (2011)
  • Author(s): Ryuman N, Watanabe N, Arai T
  • Journal Title: Oxidative Medicine and Cellular Longevity Volume: 450317
• [Journal Article] Neoechinulin A impedes the progression of rotenone-induced cytotoxicity in PC12 cells (2011)
  • Author(s): Akashi S, Kimura T, Takeuchi T, Kuramochi K, Kobayashi S, Sugawara F, Watanabe N, Arai T
  • Journal Title: Biological & Pharmaceutical Bulletin Volume: 34 Pages: 243-248
• [Journal Article] Synthesis and Neuroprotective Action of Optically Pure Neoechinulin A and Its Analogs (2010)
  • Author(s): Aoki T, Ohnishi K, Kimoto M, Fujieda S, Kuramochi K, Takeuchi T, Nakazaki A, Watanabe N, Sugawara F, Arai T, Kobayashi S
  • Journal Title: Pharmaceuticals Volume: 3 Pages: 1063-1069
• [Journal Article] SIN-1 cytotoxicity to PC12 cells is mediated by thiol-sensitive short-lived substances generated through SIN-1 decomposition in culture medium (2009)
  • Author(s): Konishi K, Watanabe N, Arai T
  • Journal Title: Nitric Oxide Volume: 4 Pages: 270-278
• [Presentation] Neoechinulin A confers resistance against nitrosative stress despite inducing a significant depletion of cellular GSH (2011)
  • Author(s): Watanabe N, Akashi S, Nakagawa T, Okada T, Takeuchi T, Kuramochi K, Sugawara F, Kobayashi S, Arai T
  • Organizer: 18th Annual Meeting of the Society for Free Radical Biology and Medicine
  • Place of Presentation: Atlanta, GA, USA
  • Year and Date: 2011-12-18
• [Presentation] Prolonged nitric oxide treatment induces tau aggregation in SH-SY5Y cells (2011)
  • Author(s): Takahashi M, Nonaka T, Hasegawa M, Watanabe N, Arai T
  • Organizer: 8th Annual Meeting of the Society for Free Radical Biology and Medicine
  • Place of Presentation: Atlanta, GA, USA
  • Year and Date: 2011-12-18
• [Presentation] Neoechinulin A impedes cell death induced by mitochondrial complex I inhibitor rotenone (2011)
  • Author(s): Akashi S, Kimura T, Takeuchi T, Kuramochi K, Kobayashi S, Sugawara F, Watanabe N, Arai T
  • Organizer: 18th Annual Meeting of the Society for Free Radical Biology and Medicine
  • Place of Presentation: Atlanta, GA, USA
  • Year and Date: 2011-12-18
• [Presentation] The mechanistic study of cytotoxicity induced by SIN-1 in PC12 cells (2011)
  • Author(s): Okada T, Konishi K, Nakashima M, Watanabe N, Arai T
  • Organizer: 5th Biannual Meeting of the Society for Free Radical Research-Asia
  • Place of Presentation: Kagoshima, Japan
  • Year and Date: 2011-09-01
• [Presentation] Nitric oxide induces tau protein aggregation in SY5Y cells (2011)
  • Author(s): Takahashi M, Chin Y, Hasegawa M, Nonaka T, Watanabe N, Arai T
  • Organizer: 5th Biannual Meeting of the Society for Free Radical Research-Asia
  • Place of Presentation: Kagoshima, Japan
  • Year and Date: 2011-09-01
• [Presentation] Neoechinulin A confers cytoprotection against nitrosative stresses in PC12 cells while paradoxically decreasing GSH contents (2011)
  • Author(s): Nakagawa T, Akashi S, Okada T, Konishi K, Ogura Y, Kuramochi K, Kobayashi S, Sugawara F, Takeuchi T, Watanabe N, Arai T
  • Organizer: 5th Biannual Meeting of the Society for Free Radical Research-Asia
  • Place of Presentation: Kagoshima, Japan
  • Year and Date: 2011-09-01
• [Presentation] SIN-1 cytotoxicity to PC12 cells is mediated by thiol-sensitive short-lived substances generated through SIN-1 decomposition in culture medium (2010)
  • Author(s): Watanabe N, Konishi K, Arai T
  • Organizer: The 6th International Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-06-14
• [Presentation] Nitric oxide induces tau protein oligomerization in SY5Y cells (2010)
  • Author(s): Takahashi M, Chin Y, Hasegawa M, Nonaka T, Watanabe N, Arai T
  • Organizer: The 6th International Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-06-14