Baldini P M, De Vito P, D'aquilio F, Vismara D, Zalfa F, Bagni C, Fiaccavento R, Di Nardo P
Department of Biology, University of Rome Tor Vergata, Rome, Italy.
Mol Cell Biochem. 2005 Apr;272(1-2):19-28. doi: 10.1007/s11010-005-4779-0.
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.
溶血磷脂酸（LPA）是一种具有多种生物学功能的脂质介质。在本研究中，我们探究了心房利钠肽（ANP），一种影响心血管稳态并在不同细胞类型中诱导抗有丝分裂作用的激素，对LPA诱导的大鼠主动脉平滑肌（RASM）细胞生长和活性氧（ROS）产生的可能作用。生理浓度的ANP完全消除了LPA对细胞生长和ROS水平的影响，而未改变LPA受体的过表达。这些作用也受到渥曼青霉素（一种磷脂酰肌醇3激酶（PI3K）抑制剂）预处理细胞的影响。此外，生理浓度的ANP完全抑制了LPA诱导的Akt（PI3K的下游靶点）激活，其也能够抑制p42/p44磷酸化。综上所述，我们的数据表明PI3K可能是LPA信号转导通路中负责RASM细胞中ROS生成和DNA合成的重要一步。同时，该酶也可能是ANP抗增殖作用的关键靶点。
