Role of atrial natriuretic peptide in the suppression of lysophosphatydic acid-induced rat aortic smooth muscle (RASM) cell growth
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Lysophosphatidic acid (LPA) is a lipid mediator with multiple biological functions. In the present study we investigated the possible role of atrial natriuretic peptide (ANP), a hormone affecting cardiovascular homeostasis and inducing antimitogenic effects in different cell types, on LPA-induced cell growth and reactive oxygen species (ROS) production in rat aortic smooth muscle (RASM) cells. Both LPA effects on cell growth and levels of ROS were totally abrogated by physiological concentrations of ANP, without modifying the overexpression of LPA-receptors. These effects were also affected by cell pretreatment with wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K). Moreover, the LPA-induced activation of Akt, a downstream target of PI3K, was completely inhibited by physiological concentrations of ANP, which were also able to inhibit p42/p44 phosphorylation. Taken together, our data suggest that PI3K may represent an important step in the LPA signal transduction pathway responsible for ROS generation and DNA synthesis in RASM cells. At same time, the enzyme could also represent an essential target for the antiproliferative effects of ANP.
Keywordsatrial natriuretic peptide lysophosphatidic acid phosphatidylinositol 3 kinase reactive oxygen species
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- 1.Anand-Srivastava MB, Trachte GJ: Atrial natriuretic factor receptors and signal transduction. Pharmacol Rev 454: 455–497, 1993Google Scholar
- 8.Levin ER, Frank HJL: Natriuretic peptides inhibit rat astroglial proliferation: Mediation by C receptor. Am J Physiol 261: 453–457, 1991Google Scholar
- 13.Jalink K, Hordijk PL, Moolenaar WH: Growth factor-like effects of lysophosphatidic acid, a novel lipid mediator. Biophys Biochim Acta 1198: 185–196, 1994Google Scholar
- 17.Yart A, Chap H, Raynal P: Phosphoinositide 3-kinases in lysophosphatidic acid signalling: Regulation and cross-talk with Ras/mitogen-activated protein kinase pathway. Biochim Biophys Acta ([0-9]+): 107–111, 2002Google Scholar
- 22.Ross RJ: The smooth muscle cell II. Growth of muscle in culture and formation of elastic fibers. J Cell Physiol 50: 171–186, 1971Google Scholar
- 23.Sambrook J, Fritsch E F, Maniatis T: Laboratory Manual. Molecular Cloning. A Second Edition, Cold Spring Harbor Laboratory Press, New York, 1989Google Scholar
- 24.Baldini PM, De Vito P, Martino A, Fraziano M, Grimaldi C, Luly P, Zalfa F, Colizzi V: Differential sensitivity of human monocytes and macrophages to ANP: A role of intracellular pH on reactive oxygen species production through the phospholipases involvement. J Leukoc Biol 73: 502–510, 2003CrossRefPubMedGoogle Scholar
- 35.Bilzer M, Jaeschke H, Vollmar AM, Paumgartner C, Gerbers AL: Prevention of Kupffer cell-induced oxidant injury in rat liver by atrial natriuretic peptide. Am J Physiol 276: 1137–1144, 1999Google Scholar