Role of signal transduction mediated by diacylglycerol and phosphatidic acid in cardiac hypertrophy

由1，2-二酰甘油（DG）激活的蛋白激酶C在心肌肥厚的发生发展中起重要作用。心肌中DG的量受DG激酶（DGK）和磷脂酸磷酸酶的调节。本文首次报道正常大鼠心肌组织中DGK ε和DGK β是主要的同工酶，这两种同工酶在心肌梗死后心室重构过程中起着不同的作用，术后28天，结扎大鼠左心室心肌组织中DGK ε mRNA的表达水平较假手术大鼠显著降低，而DGK β mRNA的表达水平无明显变化。心肌中的DGK β蛋白从颗粒移位到胞质隔室中。此外，与假手术组相比，结扎组大鼠心肌DG含量和心肌颗粒组分中PKCδ蛋白表达显著增加。这些结果表明，DGK ε和DGK ε在压力超负荷诱导的心肌肥厚的发展中发挥不同的作用，并且这两种同工酶受到不同的调节。在心脏特异性过表达DGK ε的转基因小鼠中，由主动脉收缩诱导的心肌肥厚的程度与野生型小鼠没有差异。连续血管紧张素II输注诱导的压力超负荷也是如此。这些结果与压力超负荷诱导的大鼠心肌肥厚模型中的结果不一致。不一致结果的一个可能原因可能是在我们的转基因模型中，DGK β的转基因表达水平相对较低。需要进一步研究以解决这一问题。

Protein kinase C that is activated by 1, 2-diacylglycerol (DG) plays an important role in the development of cardiac hypertrophy. Amount of DG in myocardium is regulated by DG kinase (DGK) as well as by phosphatidic acid phosphatase. We for the first time reported that DGK ε and DGK ζ are predominant isozymes that express in normal rat myocardium and that both isozymes play distinct roles in the process of ventricular remodeling after myocardial infarction.At 28 days after operations, expression levels of DGK ε mRNA but not DGK ζ in left-ventricular myocardium significantly decreased in aortic-banded rats as compared with sham-operated rats. DGK ζ protein in the myocardium translocated from the particulate to the cytosolic compartment in aortic-banded rats. Furthermore, myocardial content of DG and PKCδ protein expression in the particulate fraction of the myocardium significantly increased in aortic-banded rats compared with sham-operated rats. These results suggest that DGK ε and DGK ζ play distinct roles in the development of pressure overload-induced cardiac hypertrophy and that the two isozymes are differentially regulated.In transgenic mice with cardiac-specific overexpression of DGK ζ, extent of cardiac hypertrophy induced by aortic constriction did not differ from that in wild-type mice. This was also the case with pressure overload induced by continuous angiotensin II infusion. These findings are not consistent with those in the rat model of pressure overload-induced cardiac hypertrophy. On possible reason for the inconsistent results may be relatively low expression levels of the transgene of DGK ζ, in our transgenic model. A further study is required to solve this issue.