Physiological functions of secreted phospholipase A_2 enzymes

2011 Fiscal Year Final Research Report

• Project/Area Number: 21390027
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: 財団法人東京都医学総合研究所 (2011); Tokyo Metropolitan Organization for Medical Research (2009-2010)
• Principal Investigator: MURAKAMI Makoto 財団法人東京都医学総合研究所, 生体分子先端研究分野, 副参事研究員 (60276607)
• Co-Investigator(Renkei-kenkyūsha): YAMAMOTO Kei 財団法人東京都医学総合研究所, 生体分子先端研究分野, 主席研究員 (30304504) ; TAKETOMI Yoshitaka 財団法人東京都医学総合研究所, 生体分子先端研究分野, 主任研究員 (40365804)
• Project Period (FY): 2009 – 2011
• Keywords: 脂質 / ホスホリパーゼ / ノックアウトマウス

Research Abstract

To explore the in vivo functions of secreted phospholipase A_2s(sPLA_2s), we analyzed knockout and transgenic mice for individual sPLA_2 isoforms. We found that(1) the two sPLA_2s, III and X, respectively regulates sperm maturation and activation in male genital tracts ;(2) sPLA_<2-> X regulates hair homeostasis, gastrointestinal lipid digestion, and neuronal functions ;(3) sPLA_<2-> IID, a dendritic cell-specific isoform, participates in resolution of contact hypersensitivity ; and(4) sPLA_<2-> V, a diet-inducible adipocyte-derived sPLA_2, plays a role in amelioration of metabolic syndrome.

Research Products

• [Journal Article] Analysis of two major intracellular phospholipase A_2s in mast cells reveals crucial contribution of cPLA_2α, not iPLA_2β, to lipid mobilization in proximal mast cells and distal fibroblasts (2011)
  • Author(s): Ueno, N., Taketomi, Y., Yamamoto, K., Hirabayashi, T., Kamei, D., Kita, Y., Shimizu, T., Shinzawa, K., Tsujimoto, Y., Ikeda, K., Taguchi, R., and Murakami, M.
  • Journal Title: J. Biol. Chem Volume: 286 Pages: 37249-37263
  • DOI: DOI:10.1074/jbc.M111.290312
  • Peer Reviewed
• [Journal Article] m-Calpain is induced in vascular endothelial cells on human atheroma and accelerates atherosclerotic lesion development through proteolytic disorganization of VE-cadherin in hypercholesterolemic mice (2011)
  • Author(s): Miyazaki, T., Taketomi, Y., Takimoto, M., Lei, X., Akita, S., Kim-Kaneyama, J., Arata, S., Ohata, H., Ota, H., Murakami, M., and Miyazaki, A.
  • Journal Title: Circulation Volume: 124 Pages: 2522-2532
  • DOI: DOI:10.1161/CIRCULATIONAHA.111.021675
  • Peer Reviewed
• [Journal Article] Hair follicular expression and function of group X secreted phospholipase A_2 in mouse skin (2011)
  • Author(s): Yamamoto, K., Taketomi, T., Isogai, Y., Miki, Y., Sato, H., Masuda, S., Nishito, Y., Morioka, K., Ishimoto, Y., Suzuki, N., Yokoya, Y., Hanasaki, K., Ishikawa, Y., Ishii, T., Kobayashi, T., Fukami, K., Ikeda, K., Nakanishi, H., Taguchi, R., and Murakami, M.
  • Journal Title: J. Biol. Chem Volume: 286 Pages: 11616-11631
  • DOI: DOI:10.1074/jbc.M110.206714
  • Peer Reviewed
• [Journal Article] Physiological roles of group X secreted phospholipase A_2 in reproduction, gastrointestinal phospholipid digestion, and neuronal function (2011)
  • Author(s): Sato, H., Isogai, Y., Masuda, S., Taketomi, Y., Miki, Y., Kamei, D., Hara, S., Kobayashi, T., Ishikawa, Y., Ishii, T., Ikeda, K., Taguchi, R., Ishimoto, Y., Suzuki, N., Yokota, Y., Hanasaki, K., Suzuki-Yamamoto, T., Yamamoto, K., and Murakami, M.
  • Journal Title: J. Biol. Chem Volume: 286 Pages: 11632-11648
  • DOI: DOI:10.1074/jbc.M110.206755
  • Peer Reviewed
• [Journal Article] Secreted phospholipase A_2 revisited (2011)
  • Author(s): Murakami, M., Taketomi, Y., Sato, H., and Yamamoto, K.
  • Journal Title: J. Biochem. Volume: 150 Pages: 233-255
  • DOI: DOI:10.1093/jb/mvr088
  • Peer Reviewed
• [Journal Article] Recent progress in phospholipase A_2 research : from cells to animals to humans (2011)
  • Author(s): Murakami, M., Taketomi, Y., Miki, Y., Sato, H., Hirabayashi, T., and Yamamoto, K.
  • Journal Title: Prog. Lipid Res Volume: 50 Pages: 152-192
  • DOI: DOI:10.1016/j.plipres.2010.12.001
  • Peer Reviewed
• [Journal Article] Mitochondrial dysfunction and reduced prostaglandin synthesis in skeletal muscle of group VIB Ca^<2+>-indpendent phospholipase A_2(iPLA_<2γ>) deficient mice (2010)
  • Author(s): Yoda, E., Hachisu, K., Taketomi, Y., Yoshida, K., Nakamura, M., Ikeda, K., Taguchi, R., Nakatani, Y., Kuwata, H., Murakami, M., Kudo, I., and Hara, S.
  • Journal Title: J. Lipid Res Volume: 51 Pages: 3003-3015
  • DOI: DOI:10.1194/jlr.M008060
  • Peer Reviewed
• [Journal Article] Group III secreted phospholipase A_2 regulates epididymal sperm maturation and fertility in mice (2010)
  • Author(s): Sato, H., Taketomi, Y., Isogai, Y., Miki, Y., Yamamoto, K., Masuda, S., Hosono, T., Arata, S., Ishikawa, Y., Ishii, T., Kobayashi, T., Nakanishi, H., Ikeda, K., Taguchi, R., Hara, S., Kudo, I., and Murakami, M.
  • Journal Title: J. Clin. Invest Volume: 120 Pages: 1400-1414
  • DOI: DOI:10.1172/JCI40494
  • Peer Reviewed
• [Journal Article] Group X phospholipase A_2 is released during sperm acrosome reaction and controls fertility outcome in mice (2010)
  • Author(s): Escoffier, J., Jemel, I., Tanemoto, A., Taketomi, Y., Payre, C., Coatrieux, C., Sato, H., Yamamoto, K., Masuda, S., Pernet-Gallay, K., Pierre, V., Hara, S., Murakami, M., De Waard, M., Lambeau, G., and Arnoult, C.
  • Journal Title: J. Clin. Invest Volume: 120 Pages: 1415-1428
  • DOI: DOI:10.1172/JCI40493
  • Peer Reviewed
• [Journal Article] Emerging roles of secreted phospholipase A_2 enzymes : lessons from transgenic and knockout mice (2010)
  • Author(s): Murakami, M., Taketomi, Y., Girard, G., Yamamoto, K., and Lambeau, G.
  • Journal Title: Biochimie Volume: 92 Pages: 561-582
  • DOI: DOI:10.1016/j.biochi.2010.03.015
  • Peer Reviewed
• [Journal Article] Group III secreted phospholipase A_2 transgenic mice spontaneously develop inflammation (2009)
  • Author(s): Sato, H., Taketomi, Y., Isogai, Y., Masuda, S., Kobayashi, T., Yamamoto, K., and Murakami, M.
  • Journal Title: Biochem. J. Volume: 421 Pages: 17-27
  • DOI: DOI:10.1042/BJ20082429
  • Peer Reviewed
• [Presentation] Searching the secrets of secreted phospholipase A_<2s> (2011)
  • Author(s): Murakami, M.
  • Organizer: The 10^<th> JBS Biofrontier Symposium : New Aspect of Phospholipid Biology and Medicine 2011
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 2011-11-15
• [Presentation] アレルギー応答を制御する新しい脂質ネットワーク (2011)
  • Author(s): 村上誠、武富芳隆
  • Organizer: 第61回日本アレルギー学会
  • Place of Presentation: 東京
  • Year and Date: 2011-11-12
• [Presentation] sPLA_2 in epidermal differentiation, acidification, and barrier function (2011)
  • Author(s): Murakami, M., Lambeau, G., Gelb, M. H., and Yamamoto, K.
  • Organizer: The 8^<th> GERLI Lipidomics Meeting
  • Place of Presentation: Lyon, France
  • Year and Date: 2011-10-28
• [Presentation] 皮膚病態生理における分泌性ホスホリパーゼA_2の機能 (2011)
  • Author(s): 山本圭、村上誠
  • Organizer: 第84回日本生化学会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-23
• [Presentation] マスト細胞を制御する新しい脂質マシナリー (2011)
  • Author(s): 武富芳隆、村上誠
  • Organizer: 第84回日本生化学会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-21
• [Presentation] Getting new insights into the functions of sPLA_2s (2011)
  • Author(s): Murakami, M., Sato, H., Taketomi, Y., and Yamamoto, K.
  • Organizer: The 12^<th> International Conference on Bioactive Lipids in Inflammation, Cancer and Related Diseases
  • Place of Presentation: Seattle, WA, USA
  • Year and Date: 2011-09-21
• [Presentation] Phospholipase A_2s in adiposity and metabolic syndrome (2011)
  • Author(s): Murakami, M.
  • Organizer: The 30^<th> Naito Conference on Membrane Dynamics and Lipid Biology
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 2011-06-30
• [Presentation] New insights into the functions of secreted phospholipase A_2s (2010)
  • Author(s): 村上誠
  • Organizer: BMB2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-10
• [Presentation] Secreted phospholipase A_2, lipid mediators, and immunity (2010)
  • Author(s): Murakami, M., Taketomi, Y., and Yamamoto, K.
  • Organizer: 14^<th> International Congress of Inflammation
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-27
• [Presentation] Emerging roles of secreted phospholipase A_2 in atherosclerosis and metabolic disorders (2010)
  • Author(s): 村上誠
  • Organizer: 第42回日本動脈硬化学会
  • Place of Presentation: 岐阜
  • Year and Date: 2010-07-16
• [Presentation] Solving the secrets of secreted phospholipase A_2s (2010)
  • Author(s): Murakami, M.
  • Organizer: FASEB Summer Research Conferences on Phospholipid Metabolism
  • Place of Presentation: Steamboat Springs, USA
  • Year and Date: 2010-06-30
• [Presentation] Biological functions of sPLA_2s (2010)
  • Author(s): Murakami, M.
  • Organizer: Keystone Symposia
  • Place of Presentation: Kyoto
  • Year and Date: 2010-06-07
• [Presentation] マスト細胞生物学における脂質ネットワーク (2010)
  • Author(s): 武富芳隆、村上誠
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-28
• [Presentation] sPLA_2ネットワーク (2009)
  • Author(s): 村上誠
  • Organizer: 日本生化学会第82年会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-24
• [Presentation] Group III phospholipase A_2 in reproduction and allergy (2009)
  • Author(s): Murakami, M.
  • Organizer: The 4^<th> International Conference on Phospholipase A_2s and Lipid Mediators
  • Place of Presentation: Tokyo
  • Year and Date: 2009-05-27
• [Book] Phospholipase A_2 and lipid mediators. Biochimie special issue (2010)
  • Author(s): Lambeau, G. and Murakami, M.
• [Remarks]
  • URL: http://www.rinshoken.or.jp/P/publication_j.html