Analysis in the regulation mechanism of oxidative stress by sphingolipid

• Project/Area Number: 23590340
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Kumamoto Health Science University (2013-2014); Kumamoto University (2011-2012)
• Principal Investigator: YANO Masato 熊本保健科学大学, 保健科学部, 准教授 (60315299)
• Co-Investigator(Renkei-kenkyūsha): OIKE Yuichi 熊本大学, 大学院医学薬学研究部, 教授 (90312321)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: スフィンゴミエリン合成酵素 / ミトコンドリア / 酸化ストレス / ミトコンドリアストレス応答 / ABCB10 / TMEM65 / 脂肪萎縮 / 呼吸鎖複合体 / リポタンパク質リパーゼ / ブルーネイティブゲル電気泳動 / スフィンゴ脂質 / 電子伝達系 / ストレス応答 / スフィンゴミエリン / セラミド

Outline of Final Research Achievements

Although it has been suggested that disorder of sphingolipid metabolism is involved in the pathogenesis of a variety of disease, the mechanism has not been fully elucidated. In this study, we analyzed sphingomyelin synthase 1 (SMS1, a sphingolipid metabolizing enzyme) deficient mice, and found that lipodystrophy observed in this mice was probably caused not only by increased oxidative stress, but also by reduction of mitochondrial function, reduced activity of lipoprotein lipase, and a decrease in fatty acid uptake. Moreover, we found that the mitochondrial stress response pathway was activated in the adipocytes of SMS1-deficient mice, and performed functional analysis of the candidate factors involved in this pathway.

Research Products

• [Journal Article] TMEM65 is a mitochondrial inner-membrane protein. (2014)
  • Author(s): Naotaka Nishimura, Tomomi Gotoh, Yuichi Oike, Masato Yano
  • Journal Title: PeerJ Volume: 2 Pages: e349-e349
  • DOI: 10.7717/peerj.349
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Increased oxidative stress impairs adipose tissue function in sphingomyelin synthase 1 null mice (2013)
  • Author(s): Masato Yano, Tadashi Yamamoto, Naotaka Nishimura, Tomomi Gotoh, Ken Watanabe, Kazutaka Ikeda, Yohei Garan, Ryo Taguchi, Koichi Node, Toshiro Okazaki, Yuichi Oike
  • Journal Title: PLOS ONE Volume: 8 Issue: 4 Pages: 1-12
  • DOI: 10.1371/journal.pone.0061380
  • Peer Reviewed
• [Presentation] スフィンゴミエリン合成酵素1欠損マウスにおける脂肪萎縮と酸化ストレスの解析 (2012)
  • Author(s): 矢野正人、山本格士、西村尚剛、加覧洋平、渡辺研、後藤知己、野出孝一、岡崎俊朗、尾池雄一.
  • Organizer: 日本生化学会
  • Place of Presentation: 博多（福岡国際会議場・マリンメッセ福岡）
• [Presentation] スフィンゴミエリン合成酵素1欠損マウスにおける脂肪肝の抑制 (2012)
  • Author(s): 山本格士、矢野正人、西村尚剛、渡辺研、後藤知己、野出孝一、岡崎俊朗、尾池雄一.
  • Organizer: 日本生化学会
  • Place of Presentation: 博多（福岡国際会議場・マリンメッセ福岡）
• [Presentation] スフィンゴ脂質代謝異常による病態発症機序の解析 (2012)
  • Author(s): 矢野正人
  • Organizer: 日本生化学会
  • Place of Presentation: 京都（国立京都国際会館）