| Project/Area Number |
22791758
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Emergency medicine
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| Research Institution | Kurume University |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2011
|
| Project Status |
Completed (Fiscal Year 2011)
|
| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 敗血症 / 心不全 / JAK/STAT / SOCS3 / ミトコンドリア / 酸化ストレ / STAT3 / 酸化ストレス |
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| Research Abstract |
Lipopolysaccharide(LPS) was injected intraperitoneally in Balb/c and cardiac-specific SOCS3 knockout mice(SOCS3-CKO). SOCS3-CKO mice showed greater survival rate than WT mice after LPS injection. Left ventricular ejection fraction(LVEF) was restored to the baseline in SOCS3-CKO mice after LPS injection. DHE positive cells in cardiomyocytes were reduced in SOCS-CKO mice. The duration and intensity of STAT3 phosphorylation after LPS injection was greater in SOCS3-CKO mice than WT mice. Bcl-xL expression was increased and cleaved caspase3 expression and cytochrome c release were decreased in SOCS3-CKO mice. SOCS3-CKO mice prevents the depletion of Oxphos complexesIandIIIafter LPS injection. We found that expressions of multiple antioxidants genes including superoxide dismutases, catalase, glutathione peroxidase, thioredoxin reductase, peroxide thioredoxin were markedly upregulated in SOCS3-KO hearts after LPS injection. Our data show that the deletion of SOCS3 in cardiomyocytes prevents the LPS-induced LV dysfunction in mice via augmenting the STAT3 signaling and stabilizing mitochondria.
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