Identification and characterization of a novel endoplasmic reticulum molecule involved in cardiomyogenic differentiation and cardiac dysfunction

2011 Fiscal Year Final Research Report

• Project/Area Number: 21590937
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: TAKAHASHI Tomosaburo 京都府立医科大学, 医学研究科, 客員講師 (20381973)
• Co-Investigator(Kenkyū-buntansha): ISODONO Koji 京都府立医科大学, 医学研究科, 助教 (50515294)
• Project Period (FY): 2009 – 2011
• Keywords: 心筋細胞 / PARM-1 / 心不全 / ERストレス / 心筋細胞分化

Research Abstract

We identified PARM-1 as a novel endoplasmic reticulum(ER)-localized protein whose expression was induced by ER stress. In cardiomyocytes, knockdown of PARM-1 increased ER stress-induced apoptosis. In P19CL6 cells, overexpression of PARM-1 increased expression of BMP and phosphorylation of Smad1/5/8, resulting in acceleration of cardiomyogenic differentiation. These results indicate that PARM-1 is an ER-localized protein which plays a protective role against ER stress in postnatal cardiomyocytes, and that PARM-1 promotes cardiomyogenic differentiation through regulating the BMP-Smad signaling pathway.

Research Products

• [Journal Article] Endothelial FGF receptor signaling accelerates atherosclerosis (2011)
  • Author(s): Che J, Okigaki M, Takahashi T, Katsume A, Adachi Y, Yamaguchi S, Matsunaga S, Takeda M, Matsui A, Kishita E, Ikeda K, Yamada H, Matsubara H
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 300 Pages: 154-161
  • DOI: DOI:10.1152/ajpheart.00075.2010
  • Peer Reviewed
• [Journal Article] PARM-1 is an endoplasmic reticulum molecule involved in endoplasmic reticulum stress-induced apoptosis in rat cardiac myocytes (2010)
  • Author(s): Isodono K, Takahashi T, Imoto H, Nakanishi N, Ogata T, Asada S, Adachi A, Ueyama T, Oh H, Matsubara H
  • Journal Title: PLoS ONE Volume: 5 Pages: e9746
  • DOI: DOI:10.1371/journal.pone.0009746
  • Peer Reviewed
• [Journal Article] Paracrine osteogenic signals via bone morphogenetic protein-2 accelerate the atherosclerotic intimal calcification in vivo (2010)
  • Author(s): Nakagawa Y, Ikeda K, Akakabe Y, Koide M, Uraoka M, Yutaka KT, Kurimoto-Nakano R, Takahashi T, Matoba S, Yamada H, Okigaki M, Matsubara H
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 30 Pages: 1908-1915
  • DOI: DOI:10.1161/ATVBAHA.110.206185
  • Peer Reviewed
• [Journal Article] Bone marrow AT1 augments neointima formation by promoting mobilization of smooth muscle progenitors via platelet-derived SDF-1α (2010)
  • Author(s): Yokoi H, Yamada H, Tsubakimoto Y, Takata H, Kawahito H, Kishida S, Kato T, Matsui A, Hirai H, Ashihara E, Maekawa T, Iwai M, Horiuchi M, Ikeda K, Takahashi T, Okigaki M, Matsubara H
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 30 Pages: 60-67
  • DOI: DOI:10.1161/ATVBAHA.109.192161
  • Peer Reviewed
• [Journal Article] Replicative senescence of vascular smooth muscle cells enhances the calcification through initiating the osteoblastic transition (2009)
  • Author(s): Nakano-Kurimoto R, Ikeda K, Uraoka M, Nakagawa Y, Yutaka K, Koide M, Takahashi T, Matoba S, Yamada H, Okigaki M, Matsubara H
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 297 Pages: 1673-1684
  • DOI: DOI:10.1152/ajpheart.00455.2009
  • Peer Reviewed
• [Journal Article] Bone marrow angiotensin AT1 receptor regulates differentiation of monocyte lineage progenitors from hematopoietic stem cells (2009)
  • Author(s): Tsubakimoto Y, Yamada H, Yokoi H, Kishida S, Takata H, Kawahito H, Matsui A, Urao N, Nozawa Y, Hirai H, Imanishi J, Ashihara E, Maekawa T, Takahashi T, Okigaki M, Matsubara H
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 29 Pages: 1529-1536
  • DOI: DOI:10.1161/ATVBAHA.109.187732
  • Peer Reviewed
• [Journal Article] Altered expression of Na^+transporters at the mRNA level in rat normal and hypertrophic myocardium (2009)
  • Author(s): Yamamoto T, Shirayama T, Takahashi T, Matsubara H
  • Journal Title: Heart Vessels Volume: 24 Pages: 54-62
  • DOI: DOI:10.1007/s00380-008-1071-8
  • Peer Reviewed
• [Journal Article] Prorenin induces ERK activation in endothelial cells to enhance neovascularization independently of the renin-angiotensin system (2009)
  • Author(s): Uraoka M, Ikeda K, Nakagawa Y, Koide M, Akakabe Y, Nakano-Kurimoto R, Takahashi T, Matoba S, Yamada H, Okigaki M, Matsubara H
  • Journal Title: Biochem Biophys Res Commun Volume: 390 Pages: 1202-1207
  • DOI: DOI:10.1016/j.bbrc.2009.10.121
  • Peer Reviewed
• [Presentation] MURC, muscle-restricted coiled-coil protein, regulates caveolae morphology and induces hypertrophy in cardiomyocytes (2010)
  • Author(s): Taniguchi T, Ogata T, Naito D, Nakanishi N, Miyagawa K, Amano K, Isodono K, Imoto H, Tagawa M, Takehara N, Asada S, Adachi A, Morimoto T, Takahashi T, Oh H, Ueyama T, Matsubara H
  • Organizer: American Heart Association(米国心臓病学術会議)
  • Place of Presentation: Chicago, USA
  • Year and Date: 20101113-17
• [Presentation] MURC induces cardiomyocyte hypertrophy through the extracellular signal-regulated kinase pathway (2010)
  • Author(s): Naito D, Ogata T, Amano K, Taniguchi T, Isodono K, Adachi A, Imoto H, Nakanishi N, Kangawa H, Takahashi T, Ueyama T, Matsubara H
  • Organizer: International Symposium on Cardiovascular Endocrinology and Metabolism
  • Place of Presentation: Nara, Japan
  • Year and Date: 20100331-0401
• [Presentation] Bone marrow angiotensin AT1 receptor regulates differentiation of Monocyte lineage progenitors from hematopoietic stem cells (2010)
  • Author(s): Yamada H, Tsubakimoto Y, Yokoi H, Kishida S, Kato T, Kawahito H, Hirai H, Ashihara E, Maekawa T, Ikeda K, Takahashi T, Okigaki M, Matsubara H
  • Organizer: International Symposium on Cardiovascular Endocrinology and Metabolism
  • Place of Presentation: Nara, Japan
  • Year and Date: 20100331-0401
• [Presentation] Bone marrow AT1 augments neointima formation by promoting mobilization of smooth muscle progenitors via platelet-derived SDF-1α (2010)
  • Author(s): Yamada H, Tsubakimoto Y, Yokoi H, Kishida S, Kato T, Kawahito H, Hirai H, Ashihara E, Maekawa T, Iwai M, Horiuchi M, Ikeda K, Takahashi T, Okigaki M, Matsubara H
  • Organizer: International Symposium on Cardiovascular Endocrinology and Metabolism
  • Place of Presentation: Nara, Japan
  • Year and Date: 20100331-0401
• [Presentation] NFAT5 is essential for mesodermal and cardiomyogenic differentiation through regulating the canonical pathway (2010)
  • Author(s): Adachi A, Takahashi T, Imoto H, Nakanishi N, Kangawa H, Ueyama T, Matsubara H
  • Organizer: 第74回日本循環器学会総会
  • Place of Presentation: 京都
  • Year and Date: 20100300
• [Presentation] Serglycin, a novel adipokine highly expressed in epicardial adipose tissue (2010)
  • Author(s): Imoto H, Takahashi T, Adachi A, Nakanishi N, Kangawa H, Ueyama T, Matsubara H
  • Organizer: 第74回日本循環器学会総会
  • Place of Presentation: 京都
  • Year and Date: 20100300
• [Presentation] PARM-1, a novel transmembrane molecule involved in endoplasmic reticulum stress-induced apoptosis in rat cardiac myocytes (2010)
  • Author(s): Isodono K, Takahashi T, Imoto H, Nakanishi N, Ogata T, Asada S, Adachi A, Kangawa H, Ueyama T, Matsubara H
  • Organizer: 第74回日本循環器学会総会
  • Place of Presentation: 京都
  • Year and Date: 20100300
• [Presentation] Downregulation of Dicer Expression by Serum Withdrawal Sensitizes Human Endothelial Cells to Apoptosis (2009)
  • Author(s): Asada S, Takahashi T, Isodono K, Imoto H, Adachi A, Ogata T, Ueyama T, Matsubara H, Oh H
  • Organizer: 第73回日本循環器学会総会
  • Place of Presentation: 大阪
  • Year and Date: 20090300
• [Book] 心筋前駆・幹細胞と臨床応用の可能性、循環器再生医学の現状と展望 (2011)
  • Author(s): 竹原有史, 高橋知三郎, 松原弘明
  • Total Pages: 85-89
  • Publisher: メディカルレビュー社