| First Author | Xie Z | Year | 2007 |
| Journal | J Biol Chem | Volume | 282 |
| Issue | 35 | Pages | 25278-89 |
| PubMed ID | 17613534 | Mgi Jnum | J:124654 |
| Mgi Id | MGI:3722199 | Doi | 10.1074/jbc.M611206200 |
| Citation | Xie Z, et al. (2007) Group VIA Phospholipase A2 (iPLA2beta) Participates in Angiotensin II-induced Transcriptional Up-regulation of Regulator of G-protein Signaling-2 in Vascular Smooth Muscle Cells. J Biol Chem 282(35):25278-89 |
| abstractText | Rgs2 (regulator of G-protein signaling-2)-deficient mice exhibit severe hypertension, and genetic variations of RGS2 occur in hypertensive patients. RGS2 mRNA up-regulation by angiotensin II (Ang II) in vascular smooth muscle cells (VSMC) is a potentially important negative feedback mechanism in blood pressure homeostasis, but how it occurs is unknown. Here we demonstrate that group VIA phospholipase A(2) (iPLA(2)beta) plays a pivotal role in Ang II-induced RGS2 mRNA up-regulation in VSMC by three independent approaches, including pharmacologic inhibition with a bromoenol lactone suicide substrate, suppression of iPLA(2)beta expression with antisense oligonucleotides, and genetic deletion in iPLA(2)beta-null mice. Selective inhibition of iPLA(2)beta by each of these approaches abolishes Ang II-induced RGS2 mRNA up-regulation. Furthermore, using adenovirus-mediated gene transfer, we demonstrate that restoration of iPLA(2)beta-expression in iPLA(2)beta-null VSMC reconstitutes the ability of Ang II to up-regulate RGS2 mRNA expression. In contrast, Ang II-induced vasodilator-stimulated phosphoprotein phosphorylation and Ang II receptor expression are unaffected. Moreover, in wild-type but not iPLA(2)beta-null VSMC, Ang II stimulates iPLA(2) enzymatic activity significantly. Both arachidonic acid and lysophosphatidylcholine, products of iPLA(2)beta action, induce RGS2 mRNA up-regulation. Inhibition of lipoxygenases, particularly 15-lipoxygenase, and cyclooxygenases, but not cytochrome P450-dependent epoxygenases inhibits Ang II- or AA-induced RGS2 mRNA expression. Moreover, RGS2 protein expression is also up-regulated by Ang II, and this is attenuated by bromoenol lactone. Disruption of the Ang II/iPLA(2)beta/RGS2 feedback pathway in iPLA(2)beta-null cells potentiates Ang II-induced vasodilator-stimulated phosphoprotein and Akt phosphorylation in a time-dependent manner. Collectively, our results demonstrate that iPLA(2)beta participates in Ang II-induced transcriptional up-regulation of RGS2 in VSMC. |
