2009 Fiscal Year Final Research Report
Analysis of glucocorticoid hormone action in cardiac myocytes
| Project/Area Number |
20790657
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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 |
Endocrinology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
YOSHIKAWA Noritada The University of Tokyo, 医科学研究所, 助教 (70396878)
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| Project Period (FY) |
2008 – 2009
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| Keywords | 内分泌学 |
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| Research Abstract |
To particularly define the role of glucocorticoid (GC)-GC receptor (GR) signaling in cardiac muscle cells, we applied a ligand-based approach involving the GR-specific agonist cortivazol (CVZ) and the GR antagonist RU-486 and performed microarray analysis using rat neonatal cardiomyocytes. Expression profiles of those genes highlighted numerous roles of glucocorticoids in various aspects of cardiac physiology, especially, cardiac metabolism. At first, we identified that glucocorticoids, via GR, induce mRNA and protein expression of a transcription factor Kruppel-like factor 15 and its downstream target genes. Moreover, we revealed that GC-GR-KLF15 axis modulates cellular branched-chain amino acid concentrations in cardiomyocytes. Second, GC-GR signaling promoted gene expression of the enzymes involved in the prostaglandin biosynthesis, including cyclooxygenase-2, phospholipase A2, and Lipocalin-type prostaglandin D synthase in cardiomyocytes. In the heart, PGD2 was the most prominently induced prostaglandin after exposure to CVZ and protected against cell death induced by anoxia/reoxygenation via the D-type prostanoid receptor and the ERK1/2-mediated pathway. Together, we may conclude that GR signaling should have distinct roles for maintenance of cardiac function, for example, in amino acid catabolism and prostaglandin biosynthesis in the heart.
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[Journal Article] Glucocorticoid protects rodent hearts from ischemia/reperfusion injury by activating lipocalin-type prostaglandin D synthase-derived PGD2 biosynthesis.2009
Author(s)
Tokudome S, Sano M, Shinmura K, Matsuhashi T, Morizane S, Moriyama H, Tamaki K, Hayashida K, Nakanishi H, Yoshikawa N, Shimizu N, Endo J, Katayama T, Murata M, Yuasa S, Kaneda R, Tomita K, Eguchi N, Urade Y, Asano K, Utsunomiya Y, Suzuki T, Taguchi R, Tanaka H, Fukuda K
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Journal Title
J Clin Invest. 119(6)
Pages: 1477-88
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[Journal Article] Ligand-based gene expression profiling reveals novel roles of glucocorticoid receptor in cardiac metabolism.2009
Author(s)
Yoshikawa N, Nagasaki M, Sano M, Tokudome S, Ueno K, Shimizu N, Imoto S, Miyano S, Suematsu M, Fukuda K, Morimoto C, Tanaka H
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Journal Title
Am J Physiol Endocrinol Metab. 296(6)
Pages: 1363-73
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