Molecular mechanism of age-related muscle atrophy: The role of deacetylation against muscle atrophy

2013 Fiscal Year Final Research Report

• Project/Area Number: 24700753
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied health science
• Research Institution: Nagasaki University (2013); The University of Tokushima (2012)
• Principal Investigator: HIRASAKA Katsuya 長崎大学, 大学院水産・環境科学総合研究科, 助教 (70432747)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 加齢 / ユビキチンリガーゼ / 脱アセチル化

Research Abstract

Proinflammatory cytokines are factors that induce ubiquitin-proteasome-dependent proteolysis in skeletal muscle, causing age-related muscle atrophy. However, a molecular mechanism of muscle atrophy caused by aging remains unclear. In the present study, we examined the role of ubiquitin-proteasome-dependent proteolysis on aging. In C2C12 myotubes, TNF-alpha treatment markedly elevated the expression of the muscle-specific ubiquitin ligase MuRF1, leading to myotube atrophy. We found that MuRF1 promoter activity was mediated by acetylation of p65, a subunit of NFkB, a downstream target of the TNF-alpha signaling pathway. In addition, the acetylation of p65 was observed in skeletal muscle of aged mice. Interestingly, we found that MuRF1 deficient mice were resistant to aged-related muscle atrophy. Thus, the inhibition of NFkB-MuRF1 signaling by deacetylation could provide a novel therapeutic approach against age-related muscle atrophy.

Research Products

• [Journal Article] Isoflavones derived from soy beans prevent MuRF1-mediated muscle atrophy in C2C12 myotubes through SIRT1 activation (2013)
  • Author(s): Hirasaka K, Maeda T, Ikeda C, Haruna M, Kohno S, Abe T, Ochi A, Mukai R, Oarada M, Teshima-Kondo S, Ohno A, Okumura Y, Terao J, Nikawa T
  • Journal Title: J Nutr Sci Vitaminol Volume: 59(4) Pages: 317-324
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/24064732
  • Peer Reviewed
• [Journal Article] Cbl-b Is a Critical Regulator of Macrophage Activation Associated with Obesity-Induced Insulin Resistance in Mice (2013)
  • Author(s): Abe T, Hirasaka K, Kagawa S, Kohno S, Ochi A, Utsunomiya K, Sakai A, Ohno A, Teshima-Kondo S, Okumura Y, Oarada M, Maekawa Y, Terao J, Mills EM, Nikawa T
  • Journal Title: Diabetes Volume: 62(6) Pages: 1957-1969
  • DOI: 10.2337/db12-0677
  • Peer Reviewed
• [Journal Article] Soy glycinin contains a functional inhibitory sequence against muscle atrophy-associated ubiquitin ligase Cbl-b (2013)
  • Author(s): Abe T, Kohno S, Yama T, Ochi A, Suto T, Hirasaka K, Ohno A, Teshima-Kondo S, Okumura Y, Oarada M, Choi I, Mukai R, Terao J, Nikawa T
  • Journal Title: Int J Endocrinol Pages: 907565
  • DOI: 10.1155/2013/907565
  • Peer Reviewed
• [Journal Article] An intracellular fragment of osteoactivin formed by ectodomain shedding translocated to the nucleoplasm and bound to RNA binding proteins (2012)
  • Author(s): Utsunomiya K, Owaki K, Okumura Y, Yano M, Oto T, Suzuki E, Tamura S, Abe T, Kohno S, Ohno A, Hirasaka K, Teshima-Kondoh S, Nikawa T
  • Journal Title: Biosci Biotechnol Biochem Volume: 76(12) Pages: 2225-2229
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/23221696
  • Peer Reviewed
• [Journal Article] Mitochondrial respiratory uncoupling promotes keratinocyte differentiation and blocks skin carcinogenesis (2012)
  • Author(s): Lago CU, Nowinski SM, Rundhaug JE, Pfeiffer ME, Kiguchi K, Hirasaka K, Yang X, Abramson EM, Bratton SB, Rho O, Colavitti R, Kenaston MA, Nikawa T, Trempus C, Digiovanni J, Fischer SM, Mills EM
  • Journal Title: Oncogene Volume: 31(44) Pages: 4725-4731
  • DOI: 10.1038/onc.2011.630
  • Peer Reviewed
• [Journal Article] Unloading stress disturbs muscle regeneration through perturbed recruitment and function of macrophages (2012)
  • Author(s): Kohno S, Yamashita Y, Abe T, Hirasaka K, Oarada M, Ohno A, Teshima-Kondo S, Higashibata A, Choi I, Mills EM, Okumura Y, Terao J, Nikawa T
  • Journal Title: J Appl Physiol Volume: 112(10) Pages: 1773-1782
  • DOI: 10.1152/japplphysiol.00103
  • Peer Reviewed
• [Journal Article] Refeeding with a high-protein diet after a 48 h fast causes acute hepatocellular injury in mice (2012)
  • Author(s): Oarada M, Tsuzuki T, Nikawa T, Kohno S, Hirasaka K, Gonoi T
  • Journal Title: Br J Nutr Volume: 107(10) Pages: 1435-1444
  • DOI: 10.1017/S0007114511004521
  • Peer Reviewed
• [Presentation] 老化による筋萎縮のメカニズム : MuRF1ノックアウトマウスを用いた解析を中心に、精神・神経疾患研究開発費「臨床試験の開始を目的とした筋ジストロフィーに対する新たな治療法の開発」 (2013)
  • Author(s): 平坂勝也、前田翼、坂下禎宏、春名真里江、安倍知紀、真板綾子、近藤茂忠、谷山茂人、橘勝康、武田伸一、二川健
  • Organizer: 平成25年度研究班会議
  • Place of Presentation: JA共済ビルカンファレンス・ホール(東京都千代田区)
  • Year and Date: 2013-12-09
• [Presentation] サルコペニアに対する筋特異的ユビキチンリガーゼMuRF1の代謝調節機構 (2013)
  • Author(s): 坂下禎宏、平坂勝也、前田翼、春名真里江、中川真莉奈、河野尚平、安倍知紀、越智ありさ、平野俊介、中川香澄、真板綾子、近藤茂忠、二川健
  • Organizer: 第46回日本栄養·食糧学会中国·四国支部大会
  • Place of Presentation: 山口県立大学(山口市)
  • Year and Date: 2013-11-17
• [Presentation] 微小重力環境下における筋萎縮の分子メカニズムの研究 (2013)
  • Author(s): 平坂勝也、安倍知紀、越智ありさ、真板綾子、近藤茂忠、谷山茂人、橘勝康、二川健
  • Organizer: 日本宇宙生物科学会・第27回大会
  • Place of Presentation: 筑波大学・大学会館ホール(つくば)(奨励賞受賞講演)
  • Year and Date: 2013-09-27
• [Presentation] サルコペニアにおけるミトコンドリア内カルシウム取り込み (2013)
  • Author(s): 平坂勝也, Edward.M Mills, 池田千佳, 春名真里江, 前田翼安, 倍知紀, 宇都宮健郎, 越智ありさ, 河野尚平, 真板綾子, 近藤茂忠, 奥村裕司, 二川健
  • Organizer: 第67回日本栄養・食糧学会大会
  • Place of Presentation: 名古屋大学東山キャンパス(名古屋市)
  • Year and Date: 2013-05-26
• [Presentation] UCP3とHax-1の相互作用によるミトコンドリアへのカルシウムイオン流入の調節機構 (2012)
  • Author(s): 池田千佳、平坂勝也、春名真里江、前田翼、越智ありさ、安倍知紀、河野尚平,山岸直子、近藤茂忠、真板綾子、奥村裕司、二川健
  • 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(福岡市)
  • Year and Date: 2012-12-15
• [Presentation] 加齢による筋萎縮におけるミトコンドリア内カルシウム取り込み機構、精神・神経疾患研究開発費「筋ジストロフーに対するトランスレーショナル・リサーチ」 (2012)
  • Author(s): 平坂勝也、池田千佳、春名真里江、前田翼、安倍知紀、宇都宮健郎、越智ありさ、真板綾子、近藤茂忠、奥村裕司、武田伸一、二川健
  • Organizer: 平成24年度武田班班会議
  • Place of Presentation: JA共済ビルカンファレンス・ホール(東京都千代田区)
  • Year and Date: 2012-12-05
• [Presentation] 加齢による筋萎縮に対する大豆ポリフェノールの効果 (2012)
  • Author(s): 前田翼、平坂勝也、池田千佳、春名真里江、河野尚平、安倍知紀、越智ありさ、永野ひかる、近藤茂忠、真板綾子、奥村裕司、二川健
  • Organizer: 第45回日本栄養・食糧学会中国・四国支部大会
  • Place of Presentation: 愛媛大学農学部(松山市)
  • Year and Date: 2012-11-18
• [Presentation] The role of uncouplingprotein 3 on oxidative stress-related muscle atorophy (2012)
  • Author(s): Katsuya Hirasaka, Hironori Yamamoto, Edward Mills, Shohei Kohno, Yomoki Abe, Chika Ikeda, Tasuku Maeda, Shigetada Kondo, Ayaki Ohno, Yuushi Okumura, Takeshi Nikawa
  • Organizer: The American Society for Bone and Mineral Research(ASBMR) Tropical Meeting, 2012
  • Place of Presentation: The Westin Kansas City at Crown Center (カンザスシティ、USA)
  • Year and Date: 2012-07-17
• [Book] 運動と運動器(筋肉・神経・骨など)「運動と栄養健康づくりのための実践指導」 (2013)
  • Author(s): 平坂勝也(分担)
  • Total Pages: 56-68
  • Publisher: 講談社サイエンティフィク
• [Remarks]
  • URL: http://www.tokushima-u.ac.jp/med/culture/seitaieiyou/