Abnormal genes and myocardial fatty acid metabolism in animal with hart dysfunction.
| Project/Area Number |
15390364
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | Niigata University of Pharmacy and Applied Life Sciences |
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Principal Investigator |
WATANABE Kenichi Niigata University of Pharmacy and Applied Life Sciences, Department of Clinical Pharmacology, Professor, 薬学部, 教授 (70175090)
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| Co-Investigator(Kenkyū-buntansha) |
MA Meilei Niigata University of Pharmacy and Applied Life Sciences, Department of Clinical Pharmacology, Lecturer, 助手 (20333536)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥12,400,000 (Direct Cost: ¥12,400,000)
Fiscal Year 2005: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2004: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2003: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Keywords | heart failure / 14-3-3 protein / cardiac apoptosis / diabetes / hypertrophy / glycogen synthase kinase / drug treatment / angiotensin / 遺伝子治療 / 肥満細胞 / 心筋細胞 / MAPK / p38MAPK / トランスジェニックマウス / シグナル伝達 |
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| Research Abstract |
Dilated cardiomyopathy is a set of heterogeneous diseases of left ventricular dysfunction of unknown etiology, which has a variety of clinical courses and pathological findings. Long-chain fatty acids are one of the major cardiac energy substrates, so understanding long-chain fatty acid metabolism may help in elucidating the mechanisms of various heart diseases. Myocardial long-chain fatty acids metabolism was decreased in rats with heart failure. Although low-dose candesartan can block increases in blood pressure with circulating angiotensin same to the extent as high-close quinapril, it does not confer sufficient protection against injury from the rennin-angiotensin system in heart failure. Carvedilol has beneficial effects and protects cardiac adrenergic neurons in dilated cardiomyopathy.
Glycogen synthase kinase (GSK) 3β is a multifunctional protein that positively regulates myocardial apoptosis and negatively regulates hypertrophy. However, the role of GSK3β in the diabetic myocardium is largely unknown. We found that GSK3β became more active (less phosphorylated at serine 9) via decreased Akt phosphorylation, in parallel to JNK activation, which correlated with increased activated caspase 3 and myocardial apoptosis 3 days after streptozotocin (STZ) injection in mice. However, 28 days after STZ injection, GSK3β became inactive, which correlated with the enhanced protein kinase C β2 and p38 MAPK expression, nuclear translocation of nuclear factor of activated T cells c3, cardiac hypertrophy and fibrosis. All of the above parameters were exacerbated in dominant negative 14-3-3 transgenic mice. Our results suggest that GSK3β together with 14-3-3 protein plays essential roles in the signaling of diabetic cardiomyopathy, and treatment with either losartan or tempol prevents these changes.
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Report
(4 results)
Research Products
(34 results)
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[Journal Article] Role of IFN-γ-inducible protein-10 (IP-10/CXCL10) in the progression of pancreatitis-like injury in mice after murine retroviral infection.2006
Author(s)
Kawauchi Y, Suzuki K, Watanabe S, Yamagiwa S, Yoneyama H, Han G, Suresh SP, Punniyakoti TV, Watanabe K, Kawachi H, Okada Y, Shimizu F, Asakura H, Aoyagi Y, Narumi S.
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Journal Title
Am J Physiol-Gastr L. (in press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Amiodarone Improves cardiac sympathetic nerve function to hold norepinephrine in the heart, prevents left ventricular remodeling, and improves cardiac function in rat dilated cardiomyopathy.2005
Author(s)
Tachikawa H, Kodama M, Watanabe K, Takahashi T, Ma M, Kashimura T, Ito M, Hirono S, Okura Y, Kato K, Hanawa H, Aizawa Y.
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Journal Title
Circulation. 111
Pages: 894-899
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Ventricular fibrillation in two cases with dilated cardiomyopathy and mechanical alternans.2005
Author(s)
Kodama M, Ramadan MM, Mitsuma W, Okamura K, Kashimura T, Tachikawa H, Ito M, Fuse K, Hirono S, Okura Y, Kato K, Hanawa H, Watanabe K, Aizawa Y.
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Journal Title
PACE. 28
Pages: 1347-1349
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Effects of angiotensin II receptor blocker (candesartan) in daunorubicin-induced cardiomyopathic rats.2005
Author(s)
Soga M, Fadia A.K, Watanabe K, Ma M, Gurusamy N, Wen J, Suresh P, Paras P, Punniyakoti V, Mito S, Kunisaki M, Tachikawa H, Kodama M, Aizawa Y.
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Journal Title
Int J Cardiol. (in Press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Comparative effects of pranidipine with amlodipine in rats with heart failure.2005
Author(s)
Punniyakoti V, Watanabe K, Ma M, Gurusamy N, Suresh P, Wen J, Paras P, Wahed Mir, Fadia A.K, Mito S, _Kunisaki M, Kodama M, Aizawa Y.
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