Regulatory mechanism of inflammation and mitochondrial function by galactolipids and SM

• Project/Area Number: 26460093
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pharmacology in pharmacy
• Research Institution: Chiba University
• Principal Investigator: Murayama Toshihiko 千葉大学, 大学院薬学研究院, 教授 (90174317)
• Co-Investigator(Renkei-kenkyūsha): NISHIDA Atsushi 千葉大学, 大学院薬学研究院, 教授 (80130029)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: スフィンゴ脂質 / セラミド / 大腸炎モデルマウス / カルジオリピン / ミトコンドリア / ラクトシルセラミド / ホスホリパーゼA2 / セラミドキナーゼ / セラミド-1-リン酸 / 大腸炎 / セラミド－１－リン酸 / スフィンゴミエリン / ガラクト脂質 / アラキドン酸

Outline of Final Research Achievements

Sphingolipids are components of cellular membranes and also act as extra- and intra-cellular signals. In the present study, I examined following problems such as roles of sphingolipids on alpha-cytosolic phospholipase A2 (cPLA2alpha) that regulates inflammatory responses, regulatory mechanisms of ceramide kinase (CerK), and roles of galactose-containing sphingolipids on these enzymes. I showed that 1) caldiolipin that mainly localizes in the mitochondria bind with and activates ceramide kinase directly, 2) a galactose-containing lipid, lactosylceramide, activated cPLA2alpha via NADPH oxidase-mediated formation of reactive oxygen species, 3) progression of experimental colitis was enhanced in CerK-knockout mice.

Research Products

• [Journal Article] Effects of Glycerophospholipids on Ceramide Kinase Activity: Cardiolipin-Affected Cellular Formation of Ceramide-1-phosphate (2016)
  • Author(s): Matsuzaki W, Takahashi H, Nakamura H, Murayama T.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 39 Issue: 10 Pages: 1708-1717
  • DOI: 10.1248/bpb.b16-00535
  • NAID: 130005598502
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cholesterol-dependent increases in glucosylceramide synthase activity in Niemann-Pick disease type C model cells: Abnormal trafficking of endogenously formed ceramide metabolites by inhibition of the enzyme (2016)
  • Author(s): Hashimoto N, Matsumoto I, Takahashi H, Ashikawa H, Nakamura H, Murayama T
  • Journal Title: Neuropharmacology Volume: 110 Pages: 458-469
  • DOI: 10.1016/j.neuropharm.2016.08.011
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Trafficking of acetyl-C16-ceramide-NBD with long-term stability and no cytotoxicity into the Golgi. (2015)
  • Author(s): Makiyama T, Nakamura H, Nagasaka N, Yamashita H, Honda T, Yamaguchi N, Nishida A, Murayama T.
  • Journal Title: Traffic Volume: 16 Pages: 476-492
  • Peer Reviewed
• [Journal Article] Sphingomyelin Regulates the Activity of Secretory Phospholipase A2 in the Plasma Membrane. (2015)
  • Author(s): Nakamura H, Wakita S, Yasufuku K, Makiyama T, Waraya M, Hashimoto N, Murayama T.
  • Journal Title: J Cell Biochem Volume: in press Issue: 9 Pages: 1898-1907
  • DOI: 10.1002/jcb.25145
  • Peer Reviewed
• [Journal Article] Trafficking of acetyl-C16-ceramide-NBD with long-term stability and no cytotoxicity into the Golgi complex. (2015)
  • Author(s): 牧山智彦，中村浩之，長坂伸夫，山下尚大，本田拓也，山口直人，西田篤司，村山俊彦
  • Journal Title: Traffic Volume: In press
  • Peer Reviewed
• [Journal Article] A novel indole compound, AWT-489, inhibits prostaglandin D2-induced CD55 expression by acting on DP prostanoid receptors as an antagonist in LS174T human colon cancer cells. (2014)
  • Author(s): Oyama S, Fujino H, Yamazaki R, Okura I, Regan JW, Awata A, Arai T, Murayama T.
  • Journal Title: Arch. Biochem. Biophys. Volume: 541 Pages: 21-29
  • DOI: 10.1016/j.abb.2013.10.023
  • Peer Reviewed
• [Journal Article] Regulation of alkaline ceramidase activity by the c-Src-mediated pathway. (2014)
  • Author(s): Sasaki H, Toyomura K, Matsuzaki W, Okamoto A, Yamaguchi N, Nakamura H, Murayama T.
  • Journal Title: Arch. Biochem. Biophys. Volume: 550-551 Pages: 12-19
  • DOI: 10.1016/j.abb.2014.03.012
  • Peer Reviewed
• [Journal Article] TRPM8 has a key role in experimental colitis-induced visceral hyperalgesia in mice (2014)
  • Author(s): Hosoya T, Matsumoto K, Tashima K, Nakamura H, Fujino H, Murayama T, Horie S
  • Journal Title: Neurogastroenterol Motil Volume: 印刷中 Issue: 8 Pages: 1112-1121
  • DOI: 10.1111/nmo.12368
  • Peer Reviewed / Open Access
• [Journal Article] Distribution of transient receptor potential cation channel subfamily V member 1-expressing nerve fibers in mouse esophagus. (2014)
  • Author(s): Matsumoto K, Hosoya T, Ishikawa E, Tashima K, Amagase K, Kato S, Murayama T, Horie S.
  • Journal Title: Histochem Cell Biol Volume: 142(6) Issue: 6 Pages: 635-644
  • DOI: 10.1007/s00418-014-1246-6
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Hydrogen sulfide-mediated regulation of contractility in the mouse ileum with electrical stimulation: roles of L-cysteine, cystathionine β-synthase, and K+ channels. (2014)
  • Author(s): Yamane S, Kanno T, Nakamura H, Fujino H, Murayama T.
  • Journal Title: Eur J Pharmacol Volume: 740 Pages: 112-120
  • DOI: 10.1016/j.ejphar.2014.06.054
  • Peer Reviewed
• [Presentation] リン酸化シグナルによるセラミドキナーゼ活性制御機構の解析． (2017)
  • Author(s): 高橋宏昌，中村浩之，村山俊彦．
  • Organizer: 日本薬学会第１３７年会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-24
• [Presentation] セラミド-1-リン酸はスフィンゴシンキナーゼ1 の活性を直接的に制御する． (2017)
  • Author(s): 西野将平，山下尚大，中村浩之，村山俊彦．
  • Organizer: 第９０回日本薬理学会年会
  • Place of Presentation: 長崎
  • Year and Date: 2017-03-15
• [Presentation] Role of phosphorylation signaling on activation of group IVA phospholipase A2 by lactosylceramide. (2016)
  • Author(s): Yamazaki R, Nakamura H, Moriyama Y, Watanabe K, Tomizawa S, Murayama T.
  • Organizer: 57the International Conference on the Bioscience of Lipids.
  • Place of Presentation: Chamonix-Mont Blanc, France,
  • Year and Date: 2016-09-04
  • Int'l Joint Research
• [Presentation] Trafficking of acetyl-C16-ceramide-NBD with long-term stability and no cytotoxicity into the Golgi complex. (2016)
  • Author(s): Nakamura H, Makiyama T, Nagasaka N, Yamashita H, Honda T, Yamaguchi N, Nishida A, Murayama T
  • Organizer: ASBMB-2016
  • Place of Presentation: San Diego, USA
  • Year and Date: 2016-04-02
  • Int'l Joint Research
• [Presentation] スフィンゴミエリンはプラズマメンブランにおいてホスホリパーゼA2の活性化を抑制する (2016)
  • Author(s): 中村浩之、脇田樹男、安福加菜、牧山智彦、藁谷未沙、橋本直宏、村山俊彦
  • Organizer: 第８９回日本薬理学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-03-09
• [Presentation] カルジオリピンによるセラミドキナーゼ活性制御機構の解明 (2015)
  • Author(s): 高橋宏昌、松嵜渉、中村浩之、村山俊彦
  • Organizer: 第１４回次世代を担う若手ファーマバイオフォーラム
  • Place of Presentation: 千葉市
  • Year and Date: 2015-09-12
• [Presentation] スフィンゴミエリンによる分泌型ホスホリパーゼA２活性制御機構の解明 (2015)
  • Author(s): 橋本直宏、中村浩之、脇田樹男、安福加菜、牧山智彦、藁谷美沙、村山俊彦
  • Organizer: 第１３２回日本薬理学会関東部会
  • Place of Presentation: 浦安市
  • Year and Date: 2015-07-04
• [Presentation] ニーマンピック病C型におけるセラミド代謝と細胞内コレステロール輸送との関わり (2015)
  • Author(s): 中村浩之、藤野道、村山俊彦
  • Organizer: 第１４回生命科学研究会
  • Place of Presentation: 神奈川県三浦市
  • Year and Date: 2015-06-26
• [Presentation] ラクトシルセラミドによる細胞質型ホスホリパーゼA2alpha活性化機構の解明 (2015)
  • Author(s): 中村浩之，森山友太，牧山智彦，山下尚大，山崎璃沙，渡邊一祥，村山俊彦
  • Organizer: 日本薬学会第１３５年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] カルジオリピンはセラミドキナーゼと結合し活性化させる． (2015)
  • Author(s): 松嵜渉，中村浩之，村山俊彦
  • Organizer: 第８３回日本薬理学会年会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] リン酸化シグナルによるCerk活性制御機構の解析 (2014)
  • Author(s): 山下尚大，中村浩之，藁谷未沙，成岡詩織，村山俊彦
  • Organizer: 第１３回次世代を担う若手ファーマバイオフォーラム２０１４
  • Place of Presentation: 富山
  • Year and Date: 2014-09-20 – 2014-09-21
• [Presentation] Lactosylceramide interacts with and activates cytosolic phosphilipase A2alpha. (2014)
  • Author(s): 中村浩之，森山友太，牧山智彦，江森俊介，山崎璃沙，村山俊彦
  • Organizer: 55th International Conference on the Bioscience of Lipids
  • Place of Presentation: Aberdeen, UK
  • Year and Date: 2014-06-23 – 2014-06-27
• [Presentation] ラクトシルセラミドによる細胞質型ホスホリパーゼA2alpha活性化機構の解明 (2014)
  • Author(s): 中村浩之，森山友太，藤野裕道，村山俊彦
  • Organizer: 第１３回生命科学研究会
  • Place of Presentation: 札幌
  • Year and Date: 2014-06-20 – 2014-06-21
• [Patent(Industrial Property Rights)] ニーマンピック病C型を予防または治療するための医薬組成物 (2015)
  • Inventor(s): 中村浩之、村山俊彦
  • Industrial Property Rights Holder: 中村浩之、村山俊彦
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2015-199969
  • Filing Date: 2015-10-08