| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2008: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
|
|---|
| 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.
|
