PHOSPHATIDIC-ACID - A POTENTIAL SIGNAL TRANSDUCER FOR CARDIAC-HYPERTROPHY

Phosphatidic acid (PA) is mainly formed by the hydrolysis of phosphati dylcholine due to the activation of phospholipase D (PLD), PA is also generated by phosphorylation of diacylglycerol (DAG) due to the action of DAG kinase and is converted to DAG under the action of PA phosphoh ydrolase. Most of the positive inotropic agents which are known to sti mulate cardiac hypertrophy, have been shown to increase the level of P A in cardiac sarcolemma. Although the growth factor-like effect of PA has been recognized in a wide variety of tissues, there is a lack of s imilar information in adult cardiomyocytes. By using single cardiomyoc ytes, we have now shown that PA increased the basal [Ca2+](i) level wi thout significant effect on the amplitude of Ca2+ transients, PA (10-5 0 mu M) also increased the [Ca2+](i) in cardiac cell suspension. PA ha s also been shown to stimulate protein synthesis in cardiomyocytes, wh ich is inhibited by a PKC inhibitor as well as a Ca2+ chelator. PA at the concentration of 1-50 mu M was observed to stimulate the activity of PLC in cardiac sarcolemma; this effect was attenuated by a PLC inhi bitor. Since DAG, formed due to the activation of PLC, is considered t o play a crucial role in regulating the activity of protein kinase C ( PKC), the positive feedback effect of PA on this pathway may be essent ial for maintaining the sustained elevation in the activity of PKC dur ing the development of cardiac hypertrophy. In view of these observati ons and other facts available in the literature, it is suggested that PA may be a potential signal transducer for the development of cardiac hypertrophy. (C) 1997 Academic Press Limited.