| Project/Area Number |
05454271
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
KUZUYA Tsunehiko Osaka Univ., Medical School., Associate Prof., 医学部, 助教授 (80150340)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIDA Masashi Osaka Univ., Medical School., Resident, 医学部・附属病院, 医員
HOSHIDA Shiro Osaka Univ., Medical School., Associate Prof., 医学部, 助手 (80238732)
HORI Masatsugu Osaka Univ., Medical School., Associate Prof., 医学部, 講師 (20124779)
TADA Michiko Osaka Univ., Medical School., Professor, 医学部, 教授 (90093434)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1994: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1993: ¥5,200,000 (Direct Cost: ¥5,200,000)
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| Keywords | hypoxia / alpha adrenergic stimulation / tolerance to ischemia / Mn-SOD / antisense oligodeoxyribonucleotides / α1‐アドレナリン刺激 / アンチセンスオリゴヌクレオチド |
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| Research Abstract |
We reported the acquisition of the tolerance to ischemia at 24 hours after sub lethal ischemia in a canine model of myocardial infarction. To examined the hypothesis that the de novo synthesis of cardiac antioxidative enzymes is the mechanism of the ischemic tolerance at late phase, We applied hypoxia-reoxygenation to cultured cardiac myocytes.
1) Hypoxia induced manganese superoxide dismutase (Mn-SOD) mRNA,protein and activity at 24 hours after hypoxia in cultured neonatal rat cardiac myocytes. Tolerance to hypoxia was also induced in the myocytes 24 hours after preceding hypoxia.
2) Antisense oligodeoxyribonucleotides to Mn-SOD mRNA inhibited the induction of Mn-SOD in the cells, in coordinated with the inhibition of the acquisition of tolerance to hypoxia.
3) alpha-1 adrenergic stimulation of cultured myocytes also induced the tolerance to hypoxia coincident with the induction of Mn-SOD.
4) Mn-SOD induction in the cells by hypoxia and alpha-1 adrenergic stimulation was abolished by the addition of c-kinase inhibitor.
These results indicate that cardiac myocytes respond to stresses such as hypoxia or alpha-1 adrenergic stimulation by de novo synthesis of intrinsic antioxidative enzyme, Mn-SOD,through c-kinase mediated mechanism.
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