Phosphatidic acid: a potential signal transducer for cardiac hypertrophy.
Phosphatidic acid (PA) is mainly formed by the hydrolysis of phosphatidylcholine 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 phosphohydrolase. Most of the positive inotropic agents which are known to stimulate cardiac hypertrophy, have been shown to increase the level of PA 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 similar information in adult cardiomyocytes. By using single cardiomyocytes, we have now shown that PA increased the basal [Ca2+]i level without significant effect on the amplitude of Ca2+ transients. PA (10-50 mu M) also increased the [Ca2+]i in cardiac cell suspension. PA has also been shown to stimulate protein synthesis in cardiomyocytes, which 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 inhibitor. Since DAG, formed due to the activation of PLC, is considered to play a crucial role in regulating the activity of protein kinase C (PKC), the positive feedback effect of PA on this pathway may be essential for maintaining the sustained elevation in the activity of PKC during the development of cardiac hypertrophy. In view of these observations and other facts available in the literature, it is suggested that PA may be a potential signal transducer for the development of cardiac hypertrophy.
Dhalla
N S
NS
St Boniface General Hospital Research Center, and Departments of Physiology and Anatomy, Faculty of Medicine University of Manitoba, Winnipeg, Manitoba, Canada.
Xu
Y J
YJ
Sheu
S S
SS
Tappia
P S
PS
Panagia
V
V
D000818:Animals; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000378:metabolism / Q000503:physiopathology*; D002455:Cell Division / Q000502:physiology; D009200:Myocardial Contraction / Q000502:physiology; D010712:Phosphatidic Acids / Q000502:physiology*; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D010712:Phosphatidic Acids; D011506:Proteins; D002118:Calcium