Role of glycosylation on the functions of cardiac calcium regulating proteins and ion channels

• Project/Area Number: 25460397
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Osaka Medical College
• Principal Investigator: Asahi Michio 大阪医科大学, 医学部, 教授 (10397614)
• Co-Investigator(Kenkyū-buntansha): 中山 博之 大阪大学, 薬学研究科, 准教授 (40581062)
• Co-Investigator(Renkei-kenkyūsha): Azuma Naoto 大阪医科大学, 医学部, 教授 (40231914)
• Research Collaborator: Ii Masaaki ; Nakagawa Takatoshi ; Moriwaki Kazumasa ; Ai Tomohiko
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: O-GlcNAc修飾 / O-GlcNAc転移酵素 / 大動脈縮窄術 / NFAT / GSK3β / ホスホランバン / STIM-1 / 糖鎖 / 心筋小胞体タンパク質

Outline of Final Research Achievements

The cardiac function in diabetic patients is often reduced, although coronary areteries are intact. Metabolic abnormality of cardiac muscle might be involved in the etiology, and the pathologic condition is named diabetic cardiomyopathy. However, the mechanism was not fully understood. In this study, we focused on O-GlcNAcylation which was augmented in diabetes, and examined how the modification affected the cardiac function. As a result, we found that some proteins related to cardiac function were inactivated by O-GlcNAcylation. The downregulation of cardiac function by O-GlcNAcylation might be one of the cause of diabetic cardiomyopathy. In the future, based on this basic research, I would like to connect it with new drug development.

Research Products

• [Journal Article] Caveolae-specific activation loop between CaMKII and L-type Ca2+ channel aggravates cardiac hypertrophy in α1-adrenergic stimulation. (2017)
  • Author(s): Tonegawa K, Otsuka W, Kumagai S, Matsunami S, Hayamizu N, Tanaka S, Moriwaki K, Obana M, Maeda M, Asahi M, Kiyonari H, Fujio Y, Nakayama H.
  • Journal Title: Am J Physiol Heart Circ Physiol. Volume: 312
  • Peer Reviewed
• [Journal Article] Phospholamban Degradation Is Induced by Phosphorylation-mediated Ubiquitination and Inhibited by Interaction with Cardiac Type Sarco(endo)plasmic Reticulum Ca2+-ATPase. (2016)
  • Author(s): Nakagawa, T., Yokoe, S., Asahi, M.
  • Journal Title: Biochem Biophys Res Commun. Volume: 472 Issue: 3 Pages: 523-30
  • DOI: 10.1016/j.bbrc.2016.03.009
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Adipose-derived stem cells exhibit high differentiation potential to cardiovascular cells in C57BL/6 mice. (2016)
  • Author(s): Nagata, H., Ii, M.; Kohbayashi, E., Hoshiga, M., Hanafusa, T., Asahi, M.
  • Journal Title: Stem Cells Transl Med. Volume: 5 Issue: 2 Pages: 141-151
  • DOI: 10.5966/sctm.2015-0083
  • Peer Reviewed
• [Journal Article] Crosstalk between PI3K and Ras pathways via protein phosphatase 2A in human ovarian clear cell carcinoma. (2015)
  • Author(s): Takai M, Nakagawa T, Tanabe A, Terai Y, Ohmichi M, Asahi M.
  • Journal Title: Cancer Biol Ther. Volume: 16(2) Issue: 2 Pages: 325-35
  • DOI: 10.1080/15384047.2014.1002362
  • Peer Reviewed / Open Access
• [Journal Article] Sonic Hedgehog signaling regulates vascular differentiation and function in human CD34 positive cells: vasculogenic CD34(+) cells with Sonic Hedgehog. (2015)
  • Author(s): Kanaya K, Masaaki I, Okazaki T, Nakamura T, Horii-Komatsu M, Alev C, Akimaru H, Kawamoto A, Akashi H, Tanaka H, Asahi M, Asahara T.
  • Journal Title: Stem Cell Res Volume: 14(2) Issue: 2 Pages: 165-76
  • DOI: 10.1016/j.scr.2015.01.003
  • Peer Reviewed / Open Access
• [Journal Article] A vascular patch prepared from thai silk fibroin and gelatin hydrogel incorporating simvastatin-micelles to recruit endothelial progenitor cells. (2015)
  • Author(s): Thitiwuthikiat P, Ii M, Saito T, Asahi M, Kanokpanont S, Tabata Y.
  • Journal Title: Tissue Eng Part A. Volume: 21(7-8) Issue: 7-8 Pages: 1309-19
  • DOI: 10.1089/ten.tea.2014.0237
  • Peer Reviewed / Open Access
• [Journal Article] Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing apoptosis. (2014)
  • Author(s): Takahara K, Ii M, Inamoto T, Komura K, Ibuki N, Minami K, Uehara H, Hirano H, Nomi H, Kiyama S, Asahi M, Azuma H.
  • Journal Title: Biochem Biophys Res Commun Volume: 446 Issue: 4 Pages: 1102-7
  • DOI: 10.1016/j.bbrc.2014.03.080
  • Peer Reviewed / Open Access
• [Journal Article] Clinical features and underlying causes of cerebral venous thrombosis in Japanese patients. (2014)
  • Author(s): Shindo A, Wada H, Ishikawa H, Ito A, Asahi M, Ii Y, Ikejiri M, Tomimoto H.
  • Journal Title: Int J Hematol. Volume: 99(4) Issue: 4 Pages: 437-40
  • DOI: 10.1007/s12185-014-1550-x
  • Peer Reviewed / Open Access
• [Journal Article] Genetic modulation of the SERCA activity does not affect the Ca2+ leak from the cardiac sarcoplasmic reticulum. (2014)
  • Author(s): Morimoto S, Hongo K, Kusakari Y, Komukai K, Kawai M, O-Uchi J, Nakayama H, Asahi M, Otsu K, Yoshimura M, Kurihara S.
  • Journal Title: Cell Calcium. Volume: 55 Issue: 1 Pages: 17-23
  • DOI: 10.1016/j.ceca.2013.10.005
  • Peer Reviewed / Open Access
• [Journal Article] Induction of erythropoietin increases the cell proliferation rate in a hypoxia‑inducible factor‑1‑dependent and ‑independent manner in renal cell carcinoma cell lines (2013)
  • Author(s): Fujisue Y, Nakagawa T, Takahara K, Inamoto T, Kiyama S, Azuma H, Asahi M.
  • Journal Title: ONCOLOGY LETTERS Volume: 5 Issue: 6 Pages: 1765-1770
  • DOI: 10.3892/ol.2013.1283
  • Peer Reviewed
• [Journal Article] b1-Adrenergic Receptor Recycles Via a Membranous Organelle, Recycling Endosome, by Binding with Sorting Nexin27 (2013)
  • Author(s): Takatoshi Nakagawa, Michio Asahi
  • Journal Title: J Membrane Biol Volume: 246 Issue: 7 Pages: 571-579
  • DOI: 10.1007/s00232-013-9571-6
  • Peer Reviewed
• [Journal Article] A small interfering RNA targeting Lnk accelerates bone fracture healing with early neovascularization (2013)
  • Author(s): Kawakami Y, Ii M, Matsumoto T, Kawamoto A, Kuroda R, Akimaru H, Mifune Y, Shoji T, Fukui T, Asahi M, Kurosaka M, Asahara T.
  • Journal Title: Laboratory Investigation Volume: 93 Issue: 9 Pages: 1036-1053
  • DOI: 10.1038/labinvest.2013.93
  • Peer Reviewed
• [Journal Article] Topical application of ex vivo expanded endothelial progenitor cells promotes vascularisation and wound healing in diabetic mice. (2012)
  • Author(s): Asai J
  • Journal Title: Int Wound J. Volume: -- Issue: 5 Pages: 527-33
  • DOI: 10.1111/j.1742-481x.2012.01010.x
  • Peer Reviewed
• [Presentation] Phospholamban is degraded via ubiquitin-proteasome pathway by pVHL in failing hearts (2017)
  • Author(s): 横江俊一, 朝日通雄
  • Organizer: 日本薬理学会学術総会
  • Place of Presentation: 長崎ブリックホール、他
  • Year and Date: 2017-03-15
• [Presentation] O－GlcNAcylation of GSK-3β exacerbates pressure overload-induced heart failure in OGT transgenic mice (2017)
  • Author(s): 松野真人, 横江俊一, 伊井正明, 朝日通雄
  • Organizer: 日本薬理学会学術総会
  • Place of Presentation: 長崎ブリックホール、他
  • Year and Date: 2017-03-15
• [Presentation] Phospholamban is localized in autophagosome in dilated cardiomyopathy mouse model, TgPLNR9C mice (2016)
  • Author(s): Shunichi yokoe, David H.MacLennan, Michio Asahi
  • Organizer: EB San Diego2016
  • Place of Presentation: San Diego Convention Center
  • Year and Date: 2016-04-01
  • Int'l Joint Research
• [Presentation] Phospholamban is located in autophagosome in dilated cardiomyopathy mouse model, TgPLNR9C mice (2016)
  • Author(s): Yokoe,S, MacLennan,DH, Asahi,M
  • Organizer: Experimental Biology
  • Place of Presentation: San Diego
  • Year and Date: 2016-04-01
  • Int'l Joint Research
• [Presentation] 心不全モデルマウス(TgPLNR9Cmice)の心臓においてホスホランバンはオートファジーで分解される」 (2016)
  • Author(s): Yokoe,S, MacLennan,DH, Asahi,M
  • Organizer: 日本薬理学会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-09
• [Presentation] Crosstalk between O-GlcNAcylation and Phosphorylation Regulates Autophagy in Diabetes Mellitus and OGT-Tg Mice Exposed to Intermittent Hypoxia (2015)
  • Author(s): 野田 拓誠、野村篤生、吉村文、加藤隆児、井尻好雄、山口雄大、泉康雄、葭山実、朝日通雄、林哲也
  • Organizer: 日本循環器学会学術集会
  • Place of Presentation: 大阪国際会議場 （グランキューブ大阪）
  • Year and Date: 2015-04-25
• [Presentation] Cross talk between PI3K and Ras pathways via protein phosphatase 2A in human ovarian clear cell carcinoma (2015)
  • Author(s): 高井 雅聡、中川孝俊、田辺晃子、寺井義人、大道正英、朝日通雄
  • Organizer: 日本薬理学会年会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-03-18
• [Presentation] O-Linked N-Acetyl Glucosamine (O-GlcNAc) Regulates Autophagy and Apoptosis in Cardiomyocytes: a Double-Edged Sword in Intermittent Hypoxia-Induced Cardiac Remodeling (2014)
  • Author(s): 中川孝俊,佐々木泉帆、渡辺明、古川裕一、野村篤生、上橋和佳、加藤隆児、井尻好雄、林哲也、朝日通雄
  • Organizer: 日本生化学会近畿支部例会
  • Place of Presentation: 京都産業大学
  • Year and Date: 2014-05-17
• [Presentation] Generation of an inhibitory antibody against claudin- 15 for modulation of intestinal epithelial barrier function (2014)
  • Author(s): 森脇一将、朝日通雄、古瀬幹夫
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 仙台国際センター
• [Presentation] Local/controlled-release statin ameliorates adipose- derived stem cell therapy in limb ischemia (2013)
  • Author(s): Shintani, T, Ii M, Asahi, M, Saito, T, Tabata, Y
  • Organizer: 14th Congress of Asian Society for Vascular Surgery
  • Place of Presentation: トルコ イスタンブール
• [Presentation] 腸管上皮細胞のバリア機能を調節する 機能阻害抗体の作製
  • Author(s): 森脇一将、朝日通雄、月田承一郎、古瀬幹夫
  • Organizer: 第60回日本生化学会近畿支部例会
  • Place of Presentation: 大阪大学吹田キャンパス
• [Remarks] 大阪医科大学生命科学講座 薬理学教室
  • URL: http://www.osaka-med.ac.jp/deps/pha/index.htm
• [Remarks] 大阪医科大学薬理学教室
  • URL: http://www.osaka-med.ac.jp/deps/pha/index.htm
• [Remarks] 大阪医科大学学術情報（英文業績）
  • URL: https://athena.osaka-med.ac.jp/rdb2007/e-select.php