The regulatory mechanism on cardiac SR proteins by O-linked N-acetyl glucosamine

• Project/Area Number: 19590306
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Osaka Medical College (2008); Osaka University (2007)
• Principal Investigator: ASAHI Michio Osaka Medical College, 医学部, 教授 (10397614)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2007: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: 糖鎖 / 筋小胞体タンパク質 / 循環器疾患 / ストレス / タンパク質 / 心筋小胞体

Research Abstract

筋小胞体カルシウムポンプ(SERCA)は、心筋の機能に重要な働きをしており、収縮、弛緩に深く関わっている。その制御タンパク質であるホスホランバン(PLN)やサルコリピン(SLN)によるSERCAの制御は心機能に重要な役割を演じている。本研究では、O型糖鎖であるO結合型NアセチルグルコサミンがPLNと結合し、そのリン酸化を制御することによりSERCAに対するその阻害活性を制御し、心機能に影響していることを見出した。

Research Products

• [Journal Article] Alterations of phospholamban function can exhibit cardiotoxic effects independent of excessive sarcoplasmic reticulum Ca2+-ATPase inhibition (2009)
  • Author(s): Schmitt JP, Ahmad F, Lorenz K, Hein L, Schulz S, Asahi M, Maclennan DH, Seidman CE, Seidman JG, Lohse MJ.
  • Journal Title: Circulation 119(3) Pages: 436-44
  • Peer Reviewed
• [Journal Article] Alterations of phospholamban function can exhibit cardiotoxic effects independent of excessive sarcoplasmic reticuium Ca2+-ATPase inhibition. (2009)
  • Author(s): Schmitt JP
  • Journal Title: Circulation 119(3) Pages: 436-44
  • Peer Reviewed
• [Journal Article] Interaction sites among phospholamban, sarcolipin, and the sarco(endo)plasmic reticulum Ca^<2+>-ATPase (2008)
  • Author(s): Morita T, Hussain D, Asahi M, Tsuda T, Kurzydlowski K, Toyoshima C, Maclennan DH
  • Journal Title: Biochem. Biophys. Res. Commun 369(1) Pages: 188-94
  • Peer Reviewed
• [Journal Article] N-glycan of ErbB family plays a crucialrole in dimer formation and tumor promotion (2008)
  • Author(s): Takahashi M, Yokoe S, Asahi M, Lee SH, Li W, Osumi D, Miyoshi E, Taniguchi N
  • Journal Title: Biochim. Biophys. Acta 1780(3) Pages: 520-4
  • Peer Reviewed
• [Journal Article] Interaction sites among phospholmban, sarcolipin, and the sarco (endo) plasmic reticulum Ca^<2+>-ATPase (2008)
  • Author(s): Morita T
  • Journal Title: Biochem. Biophys. Res. Commun. 369(1) Pages: 188-94
  • Peer Reviewed
• [Journal Article] Identification of an inducible factor secreted by pancreatic cancer ceell lines that stimulates the production of fucosylated haptoglobin in hepatoma cells. (2008)
  • Author(s): Narisada M
  • Journal Title: Biochem Biophvs Res Commun. 377(3) Pages: 792-6
  • Peer Reviewed
• [Journal Article] N-glycan of ErbB family plays a crucial role in dimer formation and tumor promotion. (2008)
  • Author(s): Motoko Takahashi
  • Journal Title: Biochim. Biophys. Acta. (In press)
  • Peer Reviewed
• [Journal Article] Interaction sites among phospholamban, sarcolipin, and the sarco (endo) plasmic reticulum Ca^<2+>-ATPase (2008)
  • Author(s): Takashi Morita
  • Journal Title: Biochem. Biophys. Res. Commun. (In press)
  • Peer Reviewed
• [Journal Article] A high expression of GDP-fucose transporter in hepatocellular carcinoma is a key factor for in creases in fucosylation (2007)
  • Author(s): Moriwaki K, Noda K, Nakagawa T, Asahi M, Yoshihara H, Taniguchi N, Hayashi N, Miyoshi E
  • Journal Title: Glycobiology 17 Pages: 131-20
  • Peer Reviewed
• [Journal Article] Progression of heart failure was suppressed by inhibition of apoptosis signal-regulating kinase 1 via transcoronary gene transfer (2007)
  • Author(s): Hikoso S, Ikeda Y, Yamaguchi O, Takeda T, Higuchi Y, Hirotani S, Kashiwase K, Yamada M, Asahi M, Matsumura Y, Nishida K, Matsuzaki M, Hori M, Otsu K.
  • Journal Title: J. Am. Coll. Cardiol 50 Pages: 453-62
  • Peer Reviewed
• [Journal Article] The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress (2007)
  • Author(s): Nakai A, Yamaguchi O, Takeda T, Higuchi Y, Hikoso S, Taniike M, Omiya S, Mizote I, Matsumura Y, Asahi M, Nishida K, Hori M, Mizushima N, Otsu K.
  • Journal Title: Nature Med 13 Pages: 619-24
  • Peer Reviewed
• [Journal Article] The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress. (2007)
  • Author(s): Atsuko Nakai
  • Journal Title: Cancer Res. 13 Pages: 619-24
  • Peer Reviewed
• [Journal Article] Progression of heart failure was suppressed by inhibition of apoptosis signal-regulating kinase 1 via transcoronary gene transfer. (2007)
  • Author(s): Shungo Hikoso
  • Journal Title: J. Am. Coll. Cardiol. 50 Pages: 453-62
  • Peer Reviewed
• [Journal Article] A high expression of GDP-fucose transporter in hepatocellular carcinoma is a key factor for increases in fucosylation. (2007)
  • Author(s): Kenji Moriwaki
  • Journal Title: Glycobiology 17 Pages: 1311-20
  • Peer Reviewed
• [Journal Article] Identification of an inducible factor secreted by pancreatic cancer cell lines that stimulates the production of fucosylated haptoglobin in hepatoma cells (2006)
  • Author(s): Narisada M, Kawamoto S, Kuwamoto K, Moriwaki K, Nakagawa T, Matsumoto H, Asahi M, Koyama N, Miyoshi E.
  • Journal Title: Biochem Biophys Res Commun 377(3) Pages: 792-6
  • Peer Reviewed
• [Presentation] ホスホランバンのO-GlcNAc修飾が糖尿病性心筋症へ及ぼす影響について (2008)
  • Author(s): 横江俊一、藤原範子、江口裕伸、崎山晴彦、吉原大作、朝日通雄、谷口直之、鈴木敬一郎
  • Organizer: 日本メーラード学会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-28
• [Presentation] ホスホラのO-GlcNAc修飾が糖尿病性心筋症へ及ぼす影響について (2008)
  • Author(s): 横江俊一
  • Organizer: 日本メーラード学会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-28
• [Presentation] O-GlcNAcylation of phospholamban induces cardiac dysfunction (2007)
  • Author(s): Yokoe S, Asahi M, Suzuki K, Taniguchi N, Miyoshi E
  • Organizer: 日本生化学会
  • Place of Presentation: Yokohama
  • Year and Date: 2007-12-13
• [Presentation] Abnormality of Glutathione Metabolism in Fut8 Null-mice (2007)
  • Author(s): Mizuno Y, Asahi M, Misumi Y, Yamauchi M, Sano M, Wang X, Taniguchi N, Miyoshi E
  • Organizer: Implic ations for Their Newborn Death
  • Place of Presentation: Yokohama
  • Year and Date: 2007-12-13
• [Presentation] Abnormality of Glutathione Metabolism in Fut8 Null-mice: Implications for Their Newborn Death (2007)
  • Author(s): Yoko Mizuno
  • Organizer: 日本生化学会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] O-GlcNAcylation of phospholamban induces cardiac dysfunction (2007)
  • Author(s): Shunichi Yokoe
  • Organizer: 日本生化学会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] O-GlcNAcylation of phospholamban induces cardiac dysfunction (2007)
  • Author(s): Yokoe S, Asahi M, Suzuki K, Taniguchi N, Miyoshi E
  • Organizer: Glycobiology2007
  • Place of Presentation: Boston
  • Year and Date: 2007-11-13
• [Presentation] Abnormality of Glutathione Metabolism in Fut8 Null-mice : Implications for Their Newborn Death (2007)
  • Author(s): Mizuno Y, Asahi M, Misumi Y, Yamauchi M, Sano M, Taniguchi N, Miyoshi E
  • Organizer: 札幌癌セミナー
  • Place of Presentation: Sapporo
• [Presentation] Abnormality of Glutathione Metabolism in Fut8 Null-mice: Implications for Their Newborn Death (2007)
  • Author(s): Yoko Mizuno
  • Organizer: 札幌癌セミナー
  • Place of Presentation: Boston
• [Book] 酸化ストレスと心血管病 (2007)
  • Author(s): 朝日通雄
  • Publisher: 日本医学出版
• [Book] The Lung Perspective (2007)
  • Author(s): 朝日通雄
  • Publisher: メディカルレビュー社