Dhalla N S, Xu Y J, Sheu S S, Tappia P S, Panagia V
St Boniface General Hospital Research Center, and Departments of Physiology and Anatomy, Faculty of Medicine University of Manitoba, Winnipeg, Manitoba, Canada.
J Mol Cell Cardiol. 1997 Nov;29(11):2865-71. doi: 10.1006/jmcc.1997.0522.
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.
磷脂酸（PA）主要由磷脂酶D（PLD）激活导致磷脂酰胆碱水解形成。PA也可由二酰基甘油（DAG）激酶作用使二酰基甘油磷酸化产生，并在PA磷酸水解酶作用下转化为DAG。已知大多数能刺激心肌肥大的正性肌力药物可使心肌肌膜中PA水平升高。尽管PA的生长因子样作用已在多种组织中得到认可，但在成年心肌细胞中缺乏类似信息。通过使用单个心肌细胞，我们现已表明PA可增加基础[Ca2+]i水平，而对Ca2+瞬变幅度无显著影响。PA（10 - 50 μM）也可增加心肌细胞悬液中的[Ca2+]i。PA还被证明可刺激心肌细胞中的蛋白质合成，这一作用可被PKC抑制剂以及Ca2+螯合剂抑制。观察到浓度为1 - 50 μM的PA可刺激心肌肌膜中PLC的活性；该作用可被PLC抑制剂减弱。由于PLC激活产生的DAG被认为在调节蛋白激酶C（PKC）活性中起关键作用，PA对该途径的正反馈作用可能对于心肌肥大发展过程中PKC活性的持续升高至关重要。鉴于这些观察结果以及文献中的其他事实，提示PA可能是心肌肥大发展的潜在信号转导分子。
