The role of ubiquitin proteasome system in cardioprotection by volatile anesthetics

• Project/Area Number: 26463081
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Osaka Kyoiku University (2015-2017); Osaka Dental University (2014)
• Principal Investigator: Miyamae Masami 大阪教育大学, 保健センター, 教授 (20298821)
• Co-Investigator(Kenkyū-buntansha): 竹村 元三 朝日大学, 歯学部, 教授 (40283311) ; 金田 一弘 大阪歯科大学, 歯学部, 講師(非常勤) (90533886)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: sevoflurane / ischemia-reperfusion / heart / ubiquitin-proteasome / guine pig / ubiquitin proteasome / guinea pig / autophagy / ubiquitin / proteasome / sevofllurane / ubiqitin system / volatile anesthetics / ischemia / reperfusion

Outline of Final Research Achievements

Administration of sevoflurane prior to ischemia-reperfusion confers cardioprotective effects (sevoflurane preconditioning). We examined the role of ubiquitin proteasome system in this protective effects. Isolated guinea pigs hearts were subjected to 30 min ischemia, followed by 120 min reperfusion (CTL). Anesthetic preconditioning was elicited with 2% sevoflurane for ten minutes prior to ischemia (SEVO). Infarct size was reduced in SEVO compared with CTL. Immunohistochemical analysis revealed that there were less myoglobin-negative cells and ubiquitin and LC 3 stain were increased in SEVO. Electron microscopic study showed that there were more abundant autophagosomes in SEVO. These results suggests that ubiquitin proteasome system plays a role in cardioprotective effects of sevoflurane associated with autophagy.

Research Products

• [Journal Article] Ultrastructural aspects of vacuolar degeneration of cardiomyocytes in human endomyocardial biopsies. (2017)
  • Author(s): Takemura G, Kanamori H, Okada H, Tsujimoto A, Miyazaki N, Takada C, Hotta Y, Takatsu Y, Fujiwara H.
  • Journal Title: Cardiovasc Pathol. Volume: 30 Pages: 64-71
  • DOI: 10.1016/j.carpath.2017.06.012
  • Peer Reviewed
• [Journal Article] Mitochondrial cardiomyopathy diagnosed with histological and genetic analyses. (2017)
  • Author(s): Kuno T, Imaeda S, Asakawa Y, Nakamura H, Takemura G, Asahara D, Numasawa Y.
  • Journal Title: Case Rep Cardiol. Volume: 2017 Pages: 9473917-9473917
  • DOI: 10.1155/2017/9473917
  • Peer Reviewed / Open Access
• [Journal Article] Three dimensional ultrastructure of capillary endothelial glycocalyx under normal and septic conditions. (2017)
  • Author(s): Okada H, Takemura G, Suzuki K, Oda K, Takada C, Hotta Y, Miyazaki N, Tsujimoto A, Muraki I, Ando Y, Zaikokuji R, Matsumoto A, Kitagaki H, Tamaoki Y, Usui T, Doi T, Yoshida T, Yoshida S, Ushikoshi H, Toyoda I, Ogura S.
  • Journal Title: Critical Care. Volume: 26 Issue: 1 Pages: 261-261
  • DOI: 10.1186/s13054-017-1841-8
  • Peer Reviewed / Open Access
• [Journal Article] Non-invasive tissue characterization of lung tumors using integrated backscatter intravascular ultrasound: An ex vivo comparative study with pathological diagnosis. (2016)
  • Author(s): Ito F, Kawasaki M, Ohno Y, Toyoshi S, Morishita M, Kaito D, Yanase K, Funaguchi N, Asano M, Endo J, Mori H, Kobayashi K, Nishigaki K, Miyazaki T, Takemura G, Minatoguchi S.
  • Journal Title: Chest. Volume: 149 Issue: 5 Pages: 1276-1284
  • DOI: 10.1378/chest.14-3042
  • Peer Reviewed
• [Journal Article] An oxidative stress biomarker, urinary 8-hydroxy-2'-deoxyguanosine, predicts cardiovascular-related death after steroid therapy for patients with active cardiac sarcoidosis. (2016)
  • Author(s): Myoren T, Kobayashi S, Oda S, Nanno T, Ishiguchi H, Murakami W, Okuda S, Okada M, Takemura G, Suga K, Matsuzaki M, Yano M.
  • Journal Title: Int J Cardiol Volume: 17 Pages: 206-213
  • DOI: 10.1016/j.ijcard.2016.03.003
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Electron microscopic findings are an important aid for diagnosing mitochondrial cardiomyopathy with mitochondrial DNA mutation 3243A>G. (2016)
  • Author(s): Takemura G, Onoue K, Kashimura T, Kanamori H, Okada H, Tsujimoto A, Miyazaki N, Nakano T, Sakaguchi Y, Saito Y.
  • Journal Title: Circulation: Heart Failure. Volume: 9 Issue: 7
  • DOI: 10.1161/circheartfailure.116.003283
  • Peer Reviewed
• [Journal Article] Long-term pathological follow-up of myocardium in a carrier of Duchenne muscular dystrophy with dilated cardiomyopathy. (2016)
  • Author(s): kondo T, Takemura et al.
  • Journal Title: Circ Hert Fail Volume: Mar;10(3)
  • NAID: 120006305563
  • Peer Reviewed
• [Journal Article] Autophagic adaptations in diabetic cardiomyopathy differ between type 1 and type 2 diabetes. (2015)
  • Author(s): Kanamori H, Takemura G, et al.
  • Journal Title: Autophagy Volume: 11 Issue: 7 Pages: 1146-1160
  • DOI: 10.1080/15548627.2015.1051295
  • Peer Reviewed
• [Journal Article] Phenotype and physiological significance of the endocardial smooth muscle cells in human failing hearts. (2015)
  • Author(s): Okada H, Takemura G, et al.
  • Journal Title: Circ Hert Fail Volume: 8 Issue: 1 Pages: 149-155
  • DOI: 10.1161/circheartfailure.114.001746
  • Peer Reviewed
• [Journal Article] Postinfarction cardiac remodeling normally proceeds in granulocyte colony-stimulating factor knockout mice. (2015)
  • Author(s): Morishita K, Takemura G, et al.
  • Journal Title: Am J Pathol Volume: 185 Issue: 7 Pages: 1899-1911
  • DOI: 10.1016/j.ajpath.2015.03.018
  • Peer Reviewed
• [Journal Article] OPC-28326, a selective peripheral vasodilator with angiogenic activity, mitigates postinfarction cardiac remodeling. (2015)
  • Author(s): Ogino A, Takemura G, et al.
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 309 Issue: 1 Pages: H213-H221
  • DOI: 10.1152/ajpheart.00062.2015
  • Peer Reviewed
• [Journal Article] MicroRNA-145 repairs infarcted myocardium by accelerating cardiomyocyte autophagy. (2015)
  • Author(s): Higashi K, Takemura G, et al.
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 309 Issue: 11 Pages: H1813-H1826
  • DOI: 10.1152/ajpheart.00709.2014
  • Peer Reviewed
• [Journal Article] Substitution of chronic insulin therapy with dipeptidyl peptidase-4 inhibitors and sodium-glucose co-transporter-2 inhibitors. (2015)
  • Author(s): Okada H, Takemura G, et al.
  • Journal Title: Diabetes Res Open J Volume: 1 Issue: 3 Pages: 77-78
  • DOI: 10.17140/droj-1-113
  • Open Access
• [Journal Article] Regular dipyridamole therapy produces sustained protection against cardiac ischemia-reperfusion injury: Is it time to revisit PARIS? (2014)
  • Author(s): Figueredo VM, Okusa C, Kaneda K, Inamura Y, Miyamae M.
  • Journal Title: International Journal of Cardiology Volume: 176 Issue: 3 Pages: 822-827
  • DOI: 10.1016/j.ijcard.2014.08.013
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Sevoflurane induces cardioprotection through reactive oxygen species-mediated upregulation of autophagy in isolated guinea pig hearts. (2013)
  • Author(s): Shiomi M, Miyamae M, Takemura G, Kaneda K, Inamura Y, Onishi A, Koshinuma S, Momota Y, Minami T, Figueredo VM.
  • Journal Title: J Anesth Volume: - Issue: 4 Pages: 593-600
  • DOI: 10.1007/s00540-013-1755-9
  • Peer Reviewed / Open Access
• [Presentation] Neutrophil Elastase Plays a Pivotal Role in Sepsis-induced Myocardial Dysfunction. (2017)
  • Author(s): Suzuki K, Okada H, Takemura G, et al.
  • Organizer: Scientific session 2017 of American Heart Association
  • Int'l Joint Research
• [Presentation] Recombinant Thrombomodulin Attenuates Sepsis-induced Myocardial Dysfunction via Protection of Endothelial Glycocalyx Structure. (2017)
  • Author(s): Yamaji F, Okada H, Takemura G, et al.
  • Organizer: Scientific session 2017 of American Heart Association
  • Int'l Joint Research
• [Presentation] リバースリモデリングはどこまで可能か？-分子機構を探るー アポトーシス、オートファジー制御による梗塞後リモデリングの改変 (2016)
  • Author(s): 竹村元三
  • Organizer: 第33回国際心臓研究会日本部会
  • Place of Presentation: 東京
  • Year and Date: 2016-12-16
  • Invited
• [Presentation] Deletion of CD28 gene exacerbates cardiac rupture and dysfunction after myocardial infarction in mice. (2016)
  • Author(s): Hirose M, Takemura G et al
  • Organizer: European Society of Cardiology 2016 annual meeting
  • Place of Presentation: Rome, Italy
  • Year and Date: 2016-08-27
  • Int'l Joint Research
• [Presentation] The role of DPP-4 in pressure overload-induced heart failure. (2016)
  • Author(s): Hirose M, Takemura et al.
  • Organizer: European Society of Cardiology 2016 annual meeting
  • Place of Presentation: Rome, Italy
  • Year and Date: 2016-08-27
  • Int'l Joint Research
• [Presentation] Highly effective treatment of endothelial disorders in sepsis by CAR peptide adjuvant for hydrocortisone therapy. (2016)
  • Author(s): Okada H, Takemura G et al.
  • Organizer: American Thoracic Society 2016 International Conference
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2016-05-13
  • Int'l Joint Research