| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
The signaling triggered by several neurohumoral factors such as angiotensin II and endothelin-1 is followed by the activation of phospholipase C which results in the production of a lipid second messenger, 1,2-diacylglycerol. 1,2-diacylglycerol serves as an activator of phospholipid-dependent protein kinase C (PKC), which elicits several cellular responses in the heart, including cardiac hypertrophy and protection of cardiomyocytes in ischemic preconditioning. Therefore, 1,2 diacyoglycerol signaling must be strictly regulated for the appropriate response. diacylglycerol kinase (DGK) is an enzyme that is responsible for controlling the 1,2-diacylglycerol cellular level by converting it to phosphatidic acid (PA), thus acting as a regulator of PKC.
To examine the involvement of diacylglycerol kinase (DGK) and phosphatidic acid phosphatase (PAP) in pressure overloaded cardiac hypertrophy, rats were subjected to either ascending aortic banding for 3, 7, and 28 days or sham operation. In comparison with sham-operated rats, the left ventricular (LV) weight of the aortic-banded rats increased progressively. At 28 days after surgery, the expression of DGKε mRNA but not DGKζ or PAP2b mRNA in the LV myocardium significantly decreased in the aortic-banded rats compared with the sham-operated rats. DGKζ protein in the LV myocardium translocated from the particulate to the cytosolic compartment in the aortic-banded rats. Furthermore, the myocardial content of 1,2-diacylglycerol and PKCδ protein expression in the particulate fraction of the LV myocardium significantly increased in aortic-banded rats compared with sham-operated rats. These results suggest that DGKε and DGKζ play distinct roles in the development of pressure overloaded cardiac hypertrophy and that the two isozymes are differentially regulated.
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