Screening and gene analysis for the protection from muscle damage by statin drugs

• Project/Area Number: 21390179
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Gifu University
• Principal Investigator: SEISHIMA Mitsuru 岐阜大学, 医学系研究科, 医学系研究科 (10171315)
• Co-Investigator(Kenkyū-buntansha): ITO Hiroyasu 岐阜大学, 大学院・医学系研究科, 講師 (80373075) ; OSAWA Yousuke 岐阜大学, 大学院・医学系研究科, 助教 (60447787) ; MORI Ichiro 岐阜大学, 大学院・医学系研究科, 助教 (40444327) ; KANAMORI Hiromitsu 岐阜大学, 医学部附属病院, 助教 (20456502) ; SAITO Kuniaki 京都大学, 医学研究科, 教授 (80262765)
• Project Period (FY): 2009 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000); Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2011: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2010: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2009: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
• Keywords: スタチン製剤 / 筋障害 / 細胞内カルシウム / リアノジン受容体 / 遺伝子解析 / フローサイトメトリー / FACS / CPTII遺伝子

Research Abstract

We determined Ca2+increase in CD19+ cells by FCM. Rosuvastatin user patients with CK elevation showed a significant increase in Ca2+ within CD19+ cells compared with that in patients without CK elevation. Out of 18 patients with an elevated Ca2+, we found out one case with a mutation in exon 34 in RyR1 gene and two cases with amutation in exon 4 in CPTII gene. These findings show that this method is useful for the screening of a mutation in genes that relate to Ca2+transport and for the prediction of muscle damage by statins.

Research Products

• [Journal Article] Resveratrol reverses remodeling in hearts with large, old myocardial infarctions through enhanced autophagy-activating AMP kinase pathway (2013)
  • Author(s): Kanamori H, Takemura G, Goto K, Tsujimoto A, Ogino A, Takeyama G, Kawaguchi T, Watanabe T, Morishita K, Kawasaki M, Mikami A, Fujiwara T, Fujiwara H, Seishima M, Minatoguchi S.
  • Journal Title: Am J Pathol Volume: 182 Issue: 3 Pages: 701-13
  • DOI: 10.1016/j.ajpath.2012.11.009
  • Peer Reviewed
• [Journal Article] Liver acid sphingomyelinase inhibits growth of metastatic colon cancer (2013)
  • Author(s): Osawa Y
  • Journal Title: J Clin Invest Volume: in press
  • Peer Reviewed
• [Journal Article] Reseveratrol reverses remodeling in hearts with large, old myocardial infarctions through enhanced autophagy-activating AMP kinase pathway (2012)
  • Author(s): Kanamori H
  • Journal Title: Am J Pathol Volume: 182 Issue: 4 Pages: 701-7013
  • DOI: 10.1016/j.jaad.2012.09.037
  • Peer Reviewed
• [Journal Article] Anti-endothelial cell antibodies in patients with cerebral small vessel diseae (2012)
  • Author(s): Kimura A
  • Journal Title: Curr Neurovasc Res Volume: 9 Pages: 296-301
  • Peer Reviewed
• [Journal Article] Pre-administration of L-tryptophan improved ADR-induced early renal failure in mice (2012)
  • Author(s): Arioka Y
  • Journal Title: Life Sci Volume: 59 Issue: 3-4 Pages: 100-106
  • DOI: 10.1016/j.lfs.2012.06.018
  • Peer Reviewed
• [Journal Article] L-tryptophan-kynurenine pathway metabolites regulate type 1 IFNs of acute viral myocarditis in mice (2012)
  • Author(s): Hoshi M
  • Journal Title: J Immunol Volume: 188 Issue: 8 Pages: 3980-3987
  • DOI: 10.4049/jimmunol.1100997
  • Peer Reviewed
• [Journal Article] L-tryptophan-mediated enhancement of susceptibility to nonalcoholic fatty liver disease is dependent on the mammalian target of rapamycin (2011)
  • Author(s): Osawa Y, Kanamori H, Seki E, Hoshi M, Ohtaki H, Yasuda Y, Ito H, Suetsugu A, Nagaki M, Moriwaki H, Saito K, Seishima M
  • Journal Title: Journal of Biological Chemistry Volume: 286 Issue: 40 Pages: 34800-34808
  • DOI: 10.1074/jbc.m111.235473
  • Peer Reviewed
• [Journal Article] Acid sphingomyelinase regulates glucose and lipid metabolism in hepatocytes through AKT activation and AMP-activated protein kinase suppression. (2011)
  • Author(s): Osawa Y, Seki E, Kodama Y, Suetsugu A, Miura K, Adachi M, Ito H, Shiratori Y, Banno Y, Olefsky JM, Nagaki M, Moriwaki H, Brenner DA, Seishima M
  • Journal Title: FASEB J Volume: 25 Issue: 4 Pages: 1133-44
  • DOI: 10.1096/fj.10-168351
  • Peer Reviewed
• [Journal Article] Autophagy limits acute myocardial infarction induced permanent coronary artery occlusion (2011)
  • Author(s): Kanamori H, et al, 15名
  • Journal Title: Am J Physiol (Heart Circ Physiol) Volume: 300 Issue: 6 Pages: 2261-2271
  • DOI: 10.1152/ajpheart.01056.2010
  • Peer Reviewed
• [Journal Article] The role of autophagy emerging in postinfarction cardiac remodelling (2011)
  • Author(s): Kanamori H, et al, 12名
  • Journal Title: Cardiovasc Res Volume: 91 Issue: 2 Pages: 330-339
  • DOI: 10.1093/cvr/cvr073
  • Peer Reviewed
• [Journal Article] Comparison of chemiluminescence enzyme immunoassay (CLEIA) with ELISA for the determination of anti-cyclic citrullinated peptide antibodies (2010)
  • Author(s): Tanaka R, Takemura M, Sato M, Yamada Y, Nakagawa T, Horibe T, Hoshi M, Ohtaki H, Ito H, Seishima M, Shimizu K.
  • Journal Title: Clin Chim Acta Volume: 411 Issue: 1-2 Pages: 22-5
  • DOI: 10.1016/j.cca.2009.09.032
  • Peer Reviewed
• [Journal Article] Statin-induced Ca^<2+> release was increased in B lymphocytes in patients who showed elevated serum creatine kinase during statin treatment. (2010)
  • Author(s): Hattori T, et al 9名
  • Journal Title: J.Atherosder Thromb Volume: 16 Pages: 870-877
  • Peer Reviewed
• [Journal Article] Comparison of chemiluminescence enzyme immunoassay (CLEIA) with ELISA for the determination of anti-cyclic citrullinated peptide antibodies. (2010)
  • Author(s): Tanaka R, et al 10名
  • Journal Title: Chn Chim Acta Volume: 411 Pages: 22-25
  • Peer Reviewed
• [Journal Article] Lipocalin-type prostaglandin D synthase and egg white cystatin react with IgE antibodies from children with egg allergy. (2010)
  • Author(s): Suzuki M, et al 9名
  • Journal Title: Allergol Int Volume: 59 Pages: 175-183
  • Peer Reviewed
• [Journal Article] Usefulness of serum cystatin C to determine the dose of vancomycin in critically ill patients (2010)
  • Author(s): Suzuki A, et al 13名
  • Journal Title: J Pharm Paharmacol Volume: 62 Pages: 901-907
  • Peer Reviewed
• [Journal Article] Ability of IDO to attenuate liver injury in alpha-galactosylceramide induced hepatitis model (2010)
  • Author(s): Ito H, et al 10名
  • Journal Title: J Immunol Volume: 185 Pages: 4554-4560
  • Peer Reviewed
• [Journal Article] Sonographic evaluation of the peripheral nerve in diabetic patients (2010)
  • Author(s): Watanabe T, et al 8名
  • Journal Title: J Ultrasound Med Volume: 29 Pages: 697-708
  • Peer Reviewed
• [Journal Article] リポ蛋白X (2010)
  • Author(s): 清島満、伊藤弘康
  • Journal Title: 日本臨床 Volume: 68 Pages: 46-49
• [Journal Article] Lp(a) (2010)
  • Author(s): 清島満、金森寛充、服部高幸
  • Journal Title: Medicina Volume: 47 Pages: 254-256
• [Journal Article] Comparison of chemiluminescence enzyme immunoassay (CLEIA) with ELISA for the determination of anti-cyclic citrullinated peptide antibodies. (2010)
  • Author(s): Tanaka R, et al 10名
  • Journal Title: Clin Chim Acta 411 Pages: 22-25
  • Peer Reviewed
• [Journal Article] Statin-induced Ca^<2+> release was increased in B lymphocytes in patients who showed elevated serum creatine kinase during statin treatment. (2010)
  • Author(s): Hattori T, et al 8名
  • Journal Title: J Atheroscler Thromb 16 Pages: 870-877
  • Peer Reviewed
• [Journal Article] Statin-induced Ca2+release wasincreased in B lymphocytes in patients who showed elevated serum creatine kinase during statin treatment. (2009)
  • Author(s): Hattori T, Saito K, Takemura M, Ito H, Ohta H, Wada H, Sei Y, Kawamura M,Seishima M.
  • Journal Title: J Atheroscler Thromb Volume: 16 Pages: 870-7
  • URL: https://www.jstage.jst.go.jp/browse/jat
  • Peer Reviewed
• [Journal Article] Sonographic evaluation of the median nerve in diabetic patients : comparison with nerve conduction studies. (2009)
  • Author(s): Watanabe T, et al 9名
  • Journal Title: J Ultrasound Med 28 Pages: 727-734
  • Peer Reviewed
• [Journal Article] Functional significance and morphological characterization of starvation induced autophagy in the adult heart. (2009)
  • Author(s): Kanamori H, et al 14名
  • Journal Title: Am J Pathol 174 Pages: 1705-1714
  • Peer Reviewed
• [Journal Article] Autophagy maintains cardiac function in the starved adult. (2009)
  • Author(s): Takemura G, et al 7名
  • Journal Title: Autophagy 5 Pages: 1034-1036
  • Peer Reviewed
• [Journal Article] 血清中HDL-コレステロールおよびLDL-コレステロール測定の勧告法-実試料の測定値を評価するための二次基準法 (2009)
  • Author(s): 柏森裕三, ほか16名
  • Journal Title: 臨床化学 38 Pages: 308-331
  • Peer Reviewed
• [Presentation] 検査情報を生かすための病態情報解析医学に学ぶ. (2012)
  • Author(s): 清島 満
  • Organizer: 第4回日本臨床一般検査学会学術集会(招待講演)
  • Place of Presentation: 岐阜市
  • Year and Date: 2012-10-27
• [Presentation] 脂質異常症の治療～動脈硬化予防の戦略として～ (2012)
  • Author(s): 清島 満
  • Organizer: 第59回日本臨床検査医学会学術集会(招待講演)
  • Place of Presentation: 京都市
• [Presentation] Is the measurement of Ca2+-release inCD19+ B cells stimulated by statin useful for prediction of muscle damage as a side effect? (2012)
  • Author(s): Mori I, Hattori T, Osawa Y, Kanamori H, Kajita K, Morita H, Ishizuka T, Saito K, Ito H, Seishima M
  • Organizer: 第44回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 福岡市
• [Presentation] 脂質異常症の治療～動脈硬化予防の戦略として～ (2012)
  • Author(s): 清島 満
  • Organizer: 第59回日本臨床検査医学学術集会
  • Place of Presentation: 京都市
  • Invited
• [Presentation] L-Trp administration can be effective in ADR-induced early renal failure through suppressing the TNF-alpha expression (2012)
  • Author(s): Arioka Y
  • Organizer: 13th ISTRY
  • Place of Presentation: Sydney
• [Presentation] Resveratrol displays cardioprotection in postinfarction remodeling through autophagic activation associated with AMPK but not sirt1 pathway (2012)
  • Author(s): Kanamori H
  • Organizer: AHA 2012
  • Place of Presentation: Los Angeles
• [Presentation] 検査情報を活かすための病態情報解析医学に学ぶ (2012)
  • Author(s): 清島 満
  • Organizer: 第4回日本臨床一般検査学会学術集会
  • Place of Presentation: 岐阜市
  • Invited
• [Presentation] 肝レチノイド貯蔵欠如マウスにおけるレチノイド代謝と肝発癌 (2012)
  • Author(s): 白上洋平
  • Organizer: 第54回日本消化器病学会大会
  • Place of Presentation: 神戸市
• [Presentation] Hepatic retinoid signaling in mouse hepatocarcinogenesis models (2012)
  • Author(s): Shirakami Y
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌市
• [Presentation] 化学発光免疫測定法を用いたプロカルシトニン測定試薬「ケミルミBRAHMSプロカルシトニン」の検討 (2012)
  • Author(s): 石田秀和
  • Organizer: 第23回日本臨床化学会東海北陸支部総会
  • Place of Presentation: 富山市
• [Presentation] Acid sphingomielinase regulates glucose and lipid metabolism in hepatocytes (2011)
  • Author(s): Osawa Y, et al, 4名
  • Organizer: DDW
  • Place of Presentation: Chicago, USA
  • Year and Date: 2011-05-10
• [Presentation] Emerging autophagy in post-myocardial infarction plays a protectiverole against progression of cardiac remodeling (2011)
  • Author(s): Kanamori H, et al, 13名
  • Organizer: 第75回日本循環器学会・学術集会
  • Place of Presentation: 横浜市
• [Presentation] Eesveratol mitigates postinfarction left ventricular adverse remodeling and cardiac dysfunction via autophagy activating AMP kinase pathway (2011)
  • Author(s): Kanamori H, et al, 13名
  • Organizer: 第15回日本心不全学会・学術集会
  • Place of Presentation: 鹿児島市
• [Presentation] Ca2+releasing effect of stains on human CD19+primary B cells. (2010)
  • Author(s): Hattori T, Saito K, Takemura M, Ito H, Ohta H, Wada H, Sei Y, Kawamura M, Seishima M
  • Organizer: 第42回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 岐阜市
  • Year and Date: 2010-06-15
• [Presentation] Ca^<2+> releasing effect of statins on human CD19+ primary B cells (2010)
  • Author(s): Hattori T, Saito K, Takemura M, Ito H, Ohta H, Wada H, Sei Y, Kawamura M, Seishima M
  • Organizer: 第42回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 岐阜市
  • Year and Date: 2010-06-15
• [Presentation] Inhibition of acid sphingomyelinasecauses hepatic glucose intolerance and insulin resistance (2010)
  • Author(s): Osawa Y, Ito H, Suetsugu A, Nagaki M, Moriwaki H, Seishima M.
  • Organizer: DDW 2010 New Orleans
  • Place of Presentation: USA
  • Year and Date: 2010-05-03
• [Presentation] Inhibition of acid sphingomyelinase causes hepatic glucose intolerance and insulin resistance (2010)
  • Author(s): Osawa Y, Ito H, Suetusgu A, Nagaki M, Moriwaki H, Seishima M
  • Organizer: DDW 2010
  • Place of Presentation: New Orlealls
  • Year and Date: 2010-05-03
• [Presentation] 高脂血症治療剤による培養細胞に対するCa2+放出効果の基礎的検討 (2010)
  • Author(s): 服部高幸、竹村正男、太田浩敏、 大澤陽介、金森寛充、伊藤弘康、斎藤邦明、清島 満
  • Organizer: 第49回日本臨床検査医学会東海・北陸支部総会 第320回日本臨床化学会東海・北陸支部例会 連合大会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-03-14
• [Presentation] 高脂血症治療剤による培養細胞に対するCa^<2+>放出効果の基礎的検討 (2010)
  • Author(s): 服部高幸、竹村正男、太田浩敏、大澤陽介、金森寛充、伊藤弘康、斎藤邦明、清島満
  • Organizer: 第49回日本臨床検査医学会東海・北陸支部総会第320回日本臨床化学会東海北陸支部例会連合大会
  • Place of Presentation: 名古屋市
  • Year and Date: 2010-03-14
• [Presentation] 高脂血症治療剤による培養細胞に対するCa^<2+>放出効果の基礎的検討 (2010)
  • Author(s): 服部高幸, ほか7名
  • Organizer: 第49回日本臨床検査医学会東海・北陸支部総会
  • Place of Presentation: 名古屋市
  • Year and Date: 2010-03-14
• [Book] 標準臨床検査医 (2012)
  • Author(s): 清島 満 標準臨床検査医学(高木 康・山田康幸編)
  • Publisher: 学医学書院, 東京
• [Book] 標準臨床検査医学 (2012)
  • Author(s): 高木 康（編集）
  • Total Pages: 413
  • Publisher: 医学書院
• [Book] 病理学入門 (2011)
  • Author(s): 清島
  • Publisher: 昭和堂, 京都
• [Book] 病理学入門 (2011)
  • Author(s): 清島満(分担執筆)内藤通孝編
  • Total Pages: 273
  • Publisher: 昭和堂
• [Remarks]
  • URL: http://www1.gifu-.ac.jp/~labmed/