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Antisense-Induced Underexpression of Manganese Superoxide Dismutase Extends Myocardial Ischemia-Reperfusion Injury

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Myocardial Ischemia and Preconditioning

Part of the book series: Progress in Experimental Cardiology ((PREC,volume 6))

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Summary

We examined the relationship between reduction of manganese superoxide dismutase (Mn-SOD) expression using an in vivo antisense oligodeoxynucleotide (AS-ODN) technique in various doses and extent of myocardial damage after ischemia-reperfusion in rats. An AS-ODN corresponding to the initiation site for Mn-SOD translation was administered intraperitoneally 24 h or 48 h before measurement of Mn-SOD protein and activity. In an infarct size-measurement study, coronary artery occlusion was performed for 20 min followed by reperfusion for 48 h at 24 h or 48 h after administration of various doses of AS-ODN. Significant decreases in the levels of Mn-SOD protein and activity were observed 48 h, but not 24 h, after administration of AS-ODN in a dose-dependent manner. Neither sense ODN nor scrambled ODN attenuated Mn-SOD activity or content. Infarct size in the groups treated with AS-ODN for 48 h, but not 24 h, was increased in a manner similar to diminution of Mn-SOD content and activity. Sense ODN or scrambled ODN did not change infarct size. In conclusion, reduced expression of Mn-SOD using AS-ODN in myocardium dose-dependently increases susceptibility to ischemia-reperfusion injury, indicating a pivotal role of this enzyme in cardioprotection.

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Authors and Affiliations

  1. Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, 565-0871, Osaka, Japan

    Shiro Hoshida M.D., Ph.D. (Vice Director), Nobushige Yamashita, Kinya Otsu & Masatsugu Hori

  2. Division of Cardiology, Osaka Rosai Hospital, Sakai, 591-8025, Osaka, Japan

    Shiro Hoshida M.D., Ph.D. (Vice Director)

Authors
  1. Shiro Hoshida M.D., Ph.D.
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  2. Nobushige Yamashita
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  3. Kinya Otsu
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  4. Masatsugu Hori
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Corresponding author

Correspondence to Shiro Hoshida M.D., Ph.D. .

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Editors and Affiliations

  1. Institute of Cardiovascular Sciences St. Boniface General Hospital Research Centre Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Naranjan S. Dhalla PhD, MD (Hon), DSc (Hon) (Distinguished Professor and Director) & Anton Lukas PhD (Associate Professor) (Distinguished Professor and Director) &  (Associate Professor)

  2. Aoto Hospital, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan

    Nobuakira Takeda MD, PhD (Associate Professor) (Associate Professor)

  3. Dept. of Pharmaceutical Sciences & Drug Research, Punjabi University, Patiala, India

    Manjeet Singh PhD (Professor & Head) (Professor & Head)

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© 2003 Springer Science+Business Media New York

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Hoshida, S., Yamashita, N., Otsu, K., Hori, M. (2003). Antisense-Induced Underexpression of Manganese Superoxide Dismutase Extends Myocardial Ischemia-Reperfusion Injury. In: Dhalla, N.S., Takeda, N., Singh, M., Lukas, A. (eds) Myocardial Ischemia and Preconditioning. Progress in Experimental Cardiology, vol 6. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0355-2_5

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  • DOI: https://doi.org/10.1007/978-1-4615-0355-2_5

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5036-1

  • Online ISBN: 978-1-4615-0355-2

  • eBook Packages: Springer Book Archive

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