The effect of aging and pressure overload on the heart of SERCA2a mutant mice
| Project/Area Number |
18590782
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Yokohama City University |
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Principal Investigator |
MINAMISAWA Susumu Yokohama City University, School of Medicine, Professor (40257332)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥2,470,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | cardiology / heypertension / gene / stress / heart failure / calcium |
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| Research Abstract |
Ca^<2+> cycling via the sarcoplasmic reticulum (SR), an extensive intracellular membrane system of Ca^<2+> store, plays a critical role in maintaining normal cardiac function as well as in development of heart diseases. Cardiac SR Ca^<2+> ATPase (SERCA2a) primarily regulates the rate of Ca^<2+> re-uptake from the cytosole to the SR lumen during relaxation in the heart. A considerable number of studies have demonstrated that the decrease in SERCA2a activity is a common feature of heart failure and that restoring SERCA2a activity prevents the development of heart failure. Phospholamban is a main endogenous inhibitor that suppresses the activity of SERCA2a. Recent studies including ours have demonstrated that mutations in the phospholamban gene are associated with human cardiomyopathy. We found a heterozygous single nucleotide transitions of the SERCA2 gene in one patients with hypertrophic cardiomyopathy. Then, we generated transgenic mice harboring V540A mutant. In addition to phospholamban, a newly identified SR protein, sarcalumenin also regulate Ca^<2+> re-uptake through the interaction with SERCA2a. Sarcalumenin is a Ca^<2+> binding glycoprotein located in the lumen of the SR and thought to regulate Ca^<2+> transport and storage in the SR. Both SERCA2a mutant TG and sarcalumenin knockout mice exhibit mild relaxation-dominant cardiac dysfunction. Here we examined the effect of aging and pressure overload stresses on these mice. These stresses promoted cardiac dysfunction in sarcalumenin KO mice, and then indicated the important role of sarcalumenin-SERCA2a interaction in maintaining cardiac function.
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Report
(3 results)
Research Products
(53 results)
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[Journal Article] Sarcalumcnin alleviates stress-induced cardiac dysfunction by improving Ca2+ handling of the sarcoplasmic reticulum2008
Author(s)
Shimura, M., Minamisawa, S., Takeshima, H., Jiao, Q., Bai, Y., Umemura, S., Ishikawa, Y
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Journal Title
Cardiovasc Res 77(2)
Pages: 362-70
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Interleukin- 15 inhibits smooth muscle cell proliferation and hyaluronan production in rat ductus arteriosus2007
Author(s)
Iwasaki, S., Minamisawa, S., Yokoyama, U., Akaike, T., Hong, Q., Nagasihima, Y., Nishimaki, S., Ishikawa, Y., Yokota, S
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Journal Title
Ped Res 62(4)
Pages: 392-8
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Maternal vitamin A alters gene profiles and structural maturation of the rat ductus arteriosus2007
Author(s)
Yokoyama, U., Sato, Y., Akaike, T., Ishida, S., Sawada, J., Nagao, T., Quan, H., Jin, M., Iwamoto, M., Yokota, S., Ishikawa, Y., Minamisawa, S
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Journal Title
Physiol Genomics 31(1)
Pages: 139-57
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Developmental changes in gene expression of Epac and its upregulation in myocardial hypertrophy2007
Author(s)
Ulucan, C., Wang, X., Baljinnyam, E., Bai, YZ., Okumura, S., Sato, M., Minamisawa, S., Hirotani, S., Ishikawa, Y
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Journal Title
Am J Physiol Heart Cric Physiol 293(3)
Pages: 1662-72
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Dopamine induces apoptosis in young, but not in neonatal, neurons via Ca^<2+>-dependent signal2007
Author(s)
Iwatsubo, K., Suzuki, S., Li, C., Tsuncmatsu, T., Nakamura, F., Okumura, S., Sato, M., Minamisawa, S., Toya, Y., Umemura, S., Ishikawa, Y
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Journal Title
Am J Physiol Cell Pkysiol 293(5)
Pages: 1498-508
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Multiple transcripts of Ca^<2+> channel subunits and a novel spliced variant of al C subunit in the rat ductus arteriosus2006
Author(s)
Yokoyama, U., Minamisawa, S., Adachi-Akahane, S.,Akaike, T., Naguro, I., Funakoshi, K., Iwamoto, M., Nakagone, M., Uemura, N., Hori, H., Yokota, S., Ishikawa, Y
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Journal Title
Am J Physiol Heart Circ Physiol 290(4)
Pages: 1660-70
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Post-transcriptional down-regulation of sarcolipin mRNA by triiodothyronine in the atrial myocardium2006
Author(s)
Minamisawa, S., Uemura, N., Sato, Y., Yokoyama, U., Yamaguchi, T., Inoue, K., Nakagone, M., Hori, H., Shimizu, M., Mochizuki, S., Ishikawa, Y
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Journal Title
FEBS letters 580(9)
Pages: 2247-2252
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Caveolin-3 inhibits growth signal in cadiac myoblasts in a Ca^<2+>-dependent manner2006
Author(s)
Fujita, T., Otsu, K., Oshikawa, J., Hori, H., Kitamura, H., Ito, T., Umemura, S., Minamisawa, S., Ishikawa, Y
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Journal Title
J Cell Mol Med 10(1)
Pages: 216-24
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Chronic activation of the prostaglandin receptor EP4 promotes hyaluronan-mediated ncointimal formation in the ductus artcriosus2006
Author(s)
Yokoyama, U., Minamisawa, S., Hong, Q., Ghatak, S., Akaikem, T, Segi-Nishida, E., Iwasaki, S., Iwamoto, M., Misra, S., Tamura, K., Hori, H., Yokota, S., Toole, BP., Sugimoto, Y., Ishikawa, Y
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Journal Title
J Clin Invest 116(11)
Pages: 3026-34
Description
「研究成果報告書概要(欧文)」より
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