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

1，2-二酰基甘油(DG)激活的蛋白激酶C在心肌肥厚的发生发展中起着重要作用。心肌中DG的含量受DG激酶(DGK)和磷脂酸磷酸酶的调节。我们首次报道了DGKε和DGKζ是在正常大鼠心肌中表达的主要同工酶，这两种同工酶在心肌梗死后的心室重构过程中起着不同的作用。术后28天，与假手术组相比，主动脉结扎大鼠左室心肌中DGKεζ的表达水平显著降低，而DGK mRNA的表达水平没有显著下降。主动脉结扎大鼠心肌DGKζ蛋白由颗粒移位至胞浆。此外，与假手术组大鼠相比，主动脉结扎大鼠心肌DG含量和心肌颗粒物中PKCδ蛋白表达显著增加。这些结果表明，Dgkε和Dgkζ在压力超负荷所致心肌肥厚的发生发展过程中起着不同的作用，并且这两种同工酶具有不同的调节作用。在心脏特异性过表达Dgkζ的转基因小鼠中，主动脉缩窄所致心肌肥厚的程度与野生型小鼠没有差别。血管紧张素II持续输注引起的压力超负荷也是如此。这些发现与压力超负荷诱导的大鼠心肌肥厚模型中的结果不一致。结果不一致的可能原因可能是在我们的转基因模型中，DGKζ转基因表达水平较低。要解决这个问题还需要进一步的研究。

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.