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Elucidation of the synthetic mechanism, disorders, and physiological functions of very long-chain fatty acids

Research Project

Project/Area Number 23370057
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionHokkaido University

Principal Investigator

KIHARA Akio  北海道大学, 薬学研究科(研究院), 教授 (50333620)

Co-Investigator(Kenkyū-buntansha) SASSA Takayuki  北海道大学, 大学院・薬学研究院, 講師 (20342793)
Co-Investigator(Renkei-kenkyūsha) OBARA Keisuke  北海道大学, 大学院・薬学研究院, 助教 (30419858)
OHNO Yusuke  北海道大学, 大学院・薬学研究院, 助教 (50611498)
Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥19,890,000 (Direct Cost: ¥15,300,000、Indirect Cost: ¥4,590,000)
Fiscal Year 2013: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Fiscal Year 2012: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2011: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywords脂質 / 代謝 / 脂肪酸 / 生体膜 / 極長鎖脂肪酸 / 皮膚バリア / スフィンゴ脂質 / 代謝異常 / ノックアウトマウス / 小胞輸送 / 皮膚 / 小胞輪送 / 皮膚バリア機能 / エンドソーム / リポソーム
Research Abstract

Although cellular level of very long-chain fatty acids (VLCFAs), which have carbon chain-length greater than 20 (>C20), is less abundant than that of long-chain fatty acids (LCFAs; C11-C20), VLCFAs possess important functions that cannot be substituted for by LCFAs and related to some disorders. In this research project, we revealed the functions of VLCFAs in skin barrier formation, relationship between metabolism of VLCFAs and several disorders such as adrenoleucodystrophy, myopathy, and mental retardation, regulatory mechanism of the VLCFA synthetic enzymes by the ceramide synthases, and the roles of VLCFAs in the vesicular transport via endosomes, by physiological and cell biological analyses using knockout mice and cultured cells, by biochemical assays using purified VLCFA synthetic enzymes, and by yeast genetical approach.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (52 results)

All 2014 2013 2012 2011 Other

All Journal Article (16 results) (of which Peer Reviewed: 15 results,  Open Access: 1 results) Presentation (27 results) (of which Invited: 3 results) Book (2 results) Remarks (7 results)

  • [Journal Article] Lorenzo's oil inhibits ELOVL1 and lowers the level of sphingomyelin with a saturated very long-chain fatty acid2014

    • Author(s)
      Sassa T, Wakashima T, Ohno Y, Kihara A
    • Journal Title

      J. Lipid Res.

      Volume: 55 Pages: 524-530

    • NAID

      120005457018

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Metabolism of very long-chain fatty acids : genes and pathophysiology2014

    • Author(s)
      Sassa T, Kihara A
    • Journal Title

      Biomol. Ther

      Volume: 22 Issue: 2 Pages: 83-92

    • DOI

      10.4062/biomolther.2014.017

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lorenzo's oil inhibits ELOVL1 and lowers the level of sphingomyelin with a saturated very long-chain fatty acid2014

    • Author(s)
      Sassa T, Wakashima T, Ohno Y, Kihara A
    • Journal Title

      Journal of lipid research

      Volume: 55 Issue: 3 Pages: 524-530

    • DOI

      10.1194/jlr.m044586

    • NAID

      120005457018

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impaired epidermal permeability barrier in mice lacking the Elovl1 gene responsible for very long-chain fatty acid production.2013

    • Author(s)
      Sassa T, Ohno Y, Suzuki S, Nomura T, Nishioka C, Kashiwagi T, Hirayama T, Akiyama M, Taguchi R, Shimizu H, Itohara S, Kihara A.
    • Journal Title

      Mol Cell Biol

      Volume: 33 Issue: 14 Pages: 2787-2796

    • DOI

      10.1128/mcb.00192-13

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Unperverted synthesis of complex sphingolipids is essential for cell survival under nitrogen starvation2013

    • Author(s)
      Yamagata M, Obara K, Kihara A
    • Journal Title

      Genes Cells

      Volume: 18 Issue: 8 Pages: 650-659

    • DOI

      10.1111/gtc.12062

    • NAID

      120005367401

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mutation for nonsyndromic mental retardation in the trans-2-enoyl-CoA reductase TER gene involved in fatty acid elongation impairs the enzyme activity and stability, leading to change in sphingolipid profile2013

    • Author(s)
      Abe K, Ohno Y, Sassa T, Taguchi R, Çali şkan, M, Ober C, Kihara A
    • Journal Title

      J. Biol. Chem.

      Volume: 288 Issue: 51 Pages: 36741-36749

    • DOI

      10.1074/jbc.m113.493221

    • NAID

      120005385316

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Congenital myopathy is caused by mutation of HACD12013

    • Author(s)
      Muhammad E, Reish O, Ohno Y, Scheetz T, Deluca A, Searby C, Regev M, Benyamini L, Fellig Y, Kihara A, Sheffield VC, Parvari R
    • Journal Title

      Hum. Mol. Genet.

      Volume: 22 Issue: 25 Pages: 5229-5236

    • DOI

      10.1093/hmg/ddt380

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cooperative synthesis of ultra long-chain fatty acid and ceramide during keratinocyte differentiation2013

    • Author(s)
      Mizutani Y, Sun H, Ohno Y, Sassa T, Wakashima T, Obara M, Yuyama K, Kihara A, Igarashi Y
    • Journal Title

      PLos One

      Volume: 8 Issue: 6 Pages: e67317-e67317

    • DOI

      10.1371/journal.pone.0067317

    • NAID

      120005322424

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects on vesicular transport pathways at the late endosome in cells with limited very long-chain fatty acids2013

    • Author(s)
      Obara K, Kojima R, Kihara A
    • Journal Title

      J. Lipid Res.

      Volume: 54 Issue: 3 Pages: 831-842

    • DOI

      10.1194/jlr.m034678

    • NAID

      120005228358

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of residues important for the catalysis, structure maintenance, and substrate specificity of yeast 3-hydroxyacyl-CoA dehydratase Phs12013

    • Author(s)
      Yazawa T, Naganuma T, Yamagata M, Kihara A
    • Journal Title

      FEBS Lett.

      Volume: 587 Issue: 6 Pages: 804-809

    • DOI

      10.1016/j.febslet.2013.02.006

    • NAID

      120005228604

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A shift in sphingolipid composition from C24 to C16 increases susceptibility to apoptosis in HeLa cells2012

    • Author(s)
      Sassa T, Suto S, Okayasu Y, Kihara A
    • Journal Title

      Biochim. Biophys. Acta

      Volume: 1821 Issue: 7 Pages: 1031-1037

    • DOI

      10.1016/j.bbalip.2012.04.008

    • NAID

      120005946698

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sphingolipids regulate the yeast high osmolarity-responsive HOG pathway2012

    • Author(s)
      Tanigawa M, Kihara A, Terashima M, Takahara T, Maeda T
    • Journal Title

      Mol. Cell. Biol

      Volume: 32 Issue: 14 Pages: 2861-2870

    • DOI

      10.1128/mcb.06111-11

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Very long-chain fatty acids : elongation, physiology and related disorders2012

    • Author(s)
      Kihara A
    • Journal Title

      J. Biochem.

      Volume: 152 Issue: 5 Pages: 387-395

    • DOI

      10.1093/jb/mvs105

    • NAID

      10031166154

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sphingolipid synthesis is involved in autophagy in Saccharomyces cerevisiae2011

    • Author(s)
      Yamagata M, Obara K, Kihara A
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 410 Issue: 4 Pages: 786-791

    • DOI

      10.1016/j.bbrc.2011.06.061

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biochemical characterization of the very long-chain fatty acid elongase ELOVL72011

    • Author(s)
      Naganuma T, Sato Y, Sassa T, Ohno Y, Kihara A
    • Journal Title

      FEBS Lett

      Volume: 585 Issue: 20 Pages: 3337-3341

    • DOI

      10.1016/j.febslet.2011.09.024

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of sphingolipids in autophagy in Saccharomyces cerevisiae2011

    • Author(s)
      Yamagata M, Obara K, Kihara A
    • Journal Title

      Chem. Phys. Lipids

      Volume: 164 Pages: S34-S35

    • DOI

      10.1016/j.chemphyslip.2011.05.110

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
  • [Presentation] The fatty acid elongase ELOVL1 and the P450 family member CYP4F22 are involved in the production of epidermal acylceramide2014

    • Author(s)
      Kihara, A
    • Organizer
      Gordon Research Conference (Glycolipid & Sphingolipid Biology)
    • Place of Presentation
      Ventura, USA
    • Year and Date
      2014-01-16
    • Related Report
      2013 Final Research Report
  • [Presentation] Fatty acid elongase Elovl1 is essential for the synthesis of ≧C26 ceramides and epidermal permeability barrier formation2014

    • Author(s)
      Sassa T, Ohno Y, Suzuki S, Nomura T, Akiyama M, Taguchi R, Shimizu H, Itohara S, Kihara A
    • Organizer
      Gordon Research Conference (Glycolipid & Sphingolipid Biology)
    • Place of Presentation
      Four Points Sheraton, Ventura, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] The condensation reaction by the fatty acid elongase ELOVL6 is stimulated by the following reduction reaction by KAR in fatty acid elongation cycle2014

    • Author(s)
      Naganuma T, Kihara A
    • Organizer
      Gordon Research Conference (Glycolipid & Sphingolipid Biology)
    • Place of Presentation
      Four Points Sheraton, Ventura, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] The fatty acid elongase ELOVL1 and the P450 family member CYP4F22 are involved in the production of epidermal acylceramide2014

    • Author(s)
      Kihara A
    • Organizer
      Gordon Research Conference (Glycolipid & Sphingolipid Biology)
    • Place of Presentation
      Four Points Sheraton, Ventura, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] 皮膚アシルセラミド産生における脂肪酸伸長酵素と水酸化酵素の解析2013

    • Author(s)
      木原章雄
    • Organizer
      第6回セラミド研究会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2013-11-07
    • Related Report
      2013 Final Research Report
  • [Presentation] 家族性精神遅滞に見られるTER P182L変異体の生化学的解析2013

    • Author(s)
      安部健介, 大野祐介, 佐々貴之, 木原章雄
    • Organizer
      日本薬学会北海道支部140回例会
    • Place of Presentation
      札幌コンベンションセンター(札幌市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 常染色体劣性遺伝精神遅滞に見られるTER P182L変異体の生化学的解析2013

    • Author(s)
      安部健介, 大野祐介, 佐々貴之, 木原章雄
    • Organizer
      第55回日本脂質生化学会
    • Place of Presentation
      ホテル松島大観荘(仙台市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] The cytochrome P450 4F subfamily protein CYP4F22 catalyzes omega-hydroxylation of ultra long-chain-containing ceramides in the epidermis2013

    • Author(s)
      Ohno Y, Ohkuni A, Kamiyama N, Kihara A
    • Organizer
      FASEB Summer Research conferences (Lysophospholipid and Other Related Mediators - From Bench to Clinic)
    • Place of Presentation
      ヒルトンニセコビレッジ(北海道)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Mice lacking the Elovl1 gene responsible for very long-chain fatty acid production exhibit neonatal lethality due to impaired epidermal permeability barrier2013

    • Author(s)
      Sassa T, Ohno Y, Suzuki S, Nomura T, Akiyama M, Taguchi R, Shimizu H, Itohara S, Kihara A
    • Organizer
      FASEB Summer Research conferences (Lysophospholipid and Other Related Mediators - From Bench to Clinic)
    • Place of Presentation
      ヒルトンニセコビレッジ(北海道)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 極長鎖脂肪酸伸長酵素Elovl1は表皮において層特異的な制御を受け皮膚バリアに必須の役割を果たす2013

    • Author(s)
      佐々貴之, 大野祐介, 鈴木翔多朗, 乃村俊史, 秋山真志, 田口良, 清水宏, 糸原重美, 木原章雄
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] アシルセラミドの合成に関与するシトクロムP450の同定2013

    • Author(s)
      大國礼, 大野祐介, 神山望, 木原章雄
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 極長鎖脂肪酸伸長酵素ELOVL6の生化学的解析2013

    • Author(s)
      永沼達郎, 木原章雄
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 家族性精神遅滞原因遺伝子TER P182L変異体の生化学的解析とスフィンゴ脂質代謝への影響について2013

    • Author(s)
      安部健介, 大野祐介, 佐々貴之, 木原章雄
    • Organizer
      第6回セラミド研究会学術集会
    • Place of Presentation
      北海道大学学術交流会館(札幌市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 皮膚アシルセラミド産生における脂肪酸伸長酵素と水酸化酵素の解析2013

    • Author(s)
      木原章雄
    • Organizer
      第6回セラミド研究会学術集会
    • Place of Presentation
      北海道大学学術交流会館(札幌市)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 極長鎖脂肪酸の生理機能の解明2012

    • Author(s)
      木原章雄
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡
    • Year and Date
      2012-12-14
    • Related Report
      2013 Final Research Report
  • [Presentation] 極長鎖脂肪酸の皮膚バリア, 小胞輸送における役割2012

    • Author(s)
      木原章雄
    • Organizer
      第54回日本脂質生化学会
    • Place of Presentation
      福岡
    • Year and Date
      2012-06-08
    • Related Report
      2013 Final Research Report
  • [Presentation] C24スフィンゴ脂質とC16スフィンゴ脂質はHeLa細胞におけるアポトーシスへ異なる影響を及ぼす2012

    • Author(s)
      佐々貴之
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      北海道大学(札幌)
    • Year and Date
      2012-03-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] Functional characterization of very long-chain sphingolipids produced by ELOVL12012

    • Author(s)
      Sassa, T
    • Organizer
      Gordon Research Conference (Glycolipid & Sphingolipid Biology)
    • Place of Presentation
      Renaissance Tuscany Il Ciocco Resort(イタリア)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 極長鎖脂肪酸の皮膚バリア, 小胞輸送における役割2012

    • Author(s)
      木原章雄
    • Organizer
      第54回日本脂質生化学会
    • Place of Presentation
      九州大学(福岡市)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 小胞輸送における極長鎖脂肪酸の機能解析2012

    • Author(s)
      小原圭介
    • Organizer
      酵母遺伝学フォーラム第45回研究報告会
    • Place of Presentation
      京都大学(宇治市)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 極長鎖脂肪酸の生理機能の解明2012

    • Author(s)
      木原章雄
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡国際会議場/マリンメッセ福岡(福岡県)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 常染色体劣性非症候性精神遅滞原因タンパク質TER P182Lの生化学的解析2012

    • Author(s)
      安部健介
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡国際会議場/マリンメッセ福岡(福岡県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 複合スフィンゴ脂質MIPC欠損酵母の窒素飢餓での細胞死とその分子メカニズム2012

    • Author(s)
      山形麻旗
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡国際会議場/マリンメッセ福岡(福岡県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] C24スフィンゴ脂質のアポトーシスにおける役割2011

    • Author(s)
      佐々貴之
    • Organizer
      第4回セラミド研究会 学術集会
    • Place of Presentation
      北海道大学(札幌)
    • Year and Date
      2011-10-28
    • Related Report
      2011 Annual Research Report
  • [Presentation] シスプラチン誘導性アポトーシスにおけるセラミドの脂肪酸鎖長の役割2011

    • Author(s)
      佐々貴之
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都国際会議場(京都)
    • Year and Date
      2011-09-22
    • Related Report
      2011 Annual Research Report
  • [Presentation] Sphingolipids with different fatty acid composition exhibit distinct physiological functions2011

    • Author(s)
      Ohno, Y.
    • Organizer
      The 30th Naito Conference on Membrane Dynamics and Lipid Biology [II]
    • Place of Presentation
      Chateraise Gateaux Kingdom Sapporo (北海道)
    • Year and Date
      2011-06-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] 極長鎖脂肪酸伸長酵素ELOVLの生化学的解析2011

    • Author(s)
      永沼達郎
    • Organizer
      日本薬学会北海道支部例会第136回例会
    • Place of Presentation
      札幌コンベンションセンター(北海道)
    • Year and Date
      2011-05-21
    • Related Report
      2011 Annual Research Report
  • [Book] 「極長鎖脂肪酸伸長とセラミド合成」ここまできたセラミド研究最前線セラミドー基礎と応用ー2011

    • Author(s)
      大野祐介, 木原章雄
    • Publisher
      食品化学新聞社
    • Related Report
      2013 Final Research Report
  • [Book] ここまできたセラミド研究最前線 セラミド-基礎と応用-2011

    • Author(s)
      大野祐介
    • Publisher
      食品化学新聞社
    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.pharm.hokudai.ac.jp/seika/index.html

    • Related Report
      2013 Final Research Report
  • [Remarks] 北海道大学薬学研究院生化学研究室

    • URL

      http://www.pharm.hokudai.ac.jp/seika/index.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] ASMBMブログ「WILD TYPES」

    • URL

      http://wildtypes.asbmb.org/2014/02/07/figuring-out-the-target-for-lorenzos-oil/

    • Related Report
      2013 Annual Research Report
  • [Remarks] Global Medical Discovery

    • URL

      http://globalmedicaldiscovery.com/key-scientific-articles/impaired-epidermal-permeability-barrier-mice-lacking-elovl1-gene-responsible-long-chain-fatty-acidproduction/

    • Related Report
      2013 Annual Research Report
  • [Remarks] 北海道大学生化学研究室

    • URL

      http://www.pharm.hokudai.ac.jp/seika/index.html

    • Related Report
      2012 Annual Research Report
  • [Remarks] MDLinx

    • URL

      http://www.mdlinx.com/cardiology/news-article.cfm/4410244

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.pharm.hokudai.ac.jp/seika/index.html

    • Related Report
      2011 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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