Identification of a cAMP-response Element in the Regulator of G-protein Signaling-2 (RGS2) Promoter as a Key Cis-regulatory Element for RGS2 Transcriptional Regulation by Angiotensin II in Cultured Vascular Smooth Muscles

被引:47
作者
Xie, Zhongwen [1 ]
Liu, Dexiang [1 ]
Liu, Shu [2 ]
Calderon, Lindsay [1 ]
Zhao, Guogang [2 ]
Turk, John [3 ]
Guo, Zhenheng [1 ]
机构
[1] Univ Kentucky, Sch Med, Dept Physiol, Lexington, KY 40536 USA
[2] Univ Kentucky, Sch Med, Dept Internal Med, Lexington, KY 40536 USA
[3] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA
基金
美国国家卫生研究院;
关键词
INDEPENDENT PHOSPHOLIPASE A(2); MEDIATES CREB PHOSPHORYLATION; BLOOD-PRESSURE REGULATION; UP-REGULATION; HYPERTENSIVE PATIENTS; RHO KINASE; EXPRESSION; GENE; CPI-17; ACTIVATION;
D O I
10.1074/jbc.M111.265462
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mice deficient in regulator of G-protein signaling-2 (RGS2) have severe hypertension, and RGS2 genetic variations occur in hypertensive humans. A potentially important negative feedback loop in blood pressure homeostasis is that angiotensin II (Ang II) increases vascular smooth muscle cell (VSMC) RGS2 expression. We reported that Group VIA phospholipase A(2) (iPLA(2)beta) is required for this response (Xie, Z., Gong, M. C., Su, W., Turk, J., and Guo, Z. (2007) J. Biol. Chem. 282, 2527825289), but the specific molecular causes and consequences of iPLA(2)beta activation are not known. Here we demonstrate that both protein kinases C (PKC) and A (PKA) participate in Ang II-induced VSMC RGS2 mRNA up-regulation, and that actions of PKC and PKA precede and follow iPLA(2)beta activation, respectively. Moreover, we identified a conserved cAMP-response element (CRE) in the murine RGS2 promoter that is critical for cAMP-response element-binding protein (CREB) binding and RGS2 promoter activation. Forskolin-stimulated RGS2 mRNA up-regulation is inhibited by CREB sequestration or specific disruption of the CREB-RGS2 promoter interaction, and Ang II-induced CREB phosphorylation and nuclear localization are blocked by iPLA(2)beta pharmacologic inhibition or genetic ablation. Ang II-induced intracellular cyclic AMP accumulation precedes CREB phosphorylation and is diminished by inhibiting iPLA2, cyclooxygenase, or lipoxygenase. Moreover, three single nucleotide polymorphisms identified in hypertensive patients are located in the human RGS2 promoter CREB binding site. Point mutations corresponding to these single nucleotide polymorphisms interfere with stimulation of human RGS2 promoter activity by forskolin. Our studies thus delineate a negative feedback loop to attenuate Ang II signaling in VSMC with potential importance in blood pressure homeostasis and the pathogenesis of human essential hypertension.
引用
收藏
页码:44646 / 44658
页数:13
相关论文
共 47 条
[1]   Involvement of group VICa2+-independent phospholipase A2 in protein kinase C-dependent arachidonic acid liberation in zymosan-stimulated macrophage-like P388D1 cells [J].
Akiba, S ;
Mizunaga, S ;
Kume, K ;
Hayama, M ;
Sato, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (28) :19906-19912
[2]  
Antonarakis SE, 1998, HUM MUTAT, V11, P1
[3]   Increased expression of regulator of G protein signaling-2 (RGS-2) in Bartter's/Gitelman's syndrome.: A role in the control of vascular tone and implication for hypertension. [J].
Calò, LA ;
Pagnin, E ;
Davis, PA ;
Sartori, M ;
Ceolotto, G ;
Pessina, AC ;
Semplicini, A .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2004, 89 (08) :4153-4157
[4]   CREB-Mediated IL-6 Expression Is Required for 15(S)-Hydroxyeicosatetraenoic Acid-Induced Vascular Smooth Muscle Cell Migration [J].
Chava, Koteswara R. ;
Karpurapu, Manjula ;
Wang, Dong ;
Bhanoori, Manjula ;
Kundumani-Sridharan, Venkatesh ;
Zhang, Qiuhua ;
Ichiki, Toshihiro ;
Glasgow, Wayne C. ;
Rao, Gadiparthi N. .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2009, 29 (06) :809-+
[5]   Characterization of the Transcriptional Regulation of the Regulator of G Protein Signaling 2 (RGS2) Gene During 3T3-L1 Preadipocyte Differentiation [J].
Cheng, Ya-Shan ;
Lee, Tzong-Shyuan ;
Hsu, Hui-Chi ;
Kou, Yu Ru ;
Wu, Yuh-Lin .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2008, 105 (03) :922-930
[6]   The aorta and heart differentially express RGS (regulators of G-protein signalling) proteins that selectively regulate sphingosine 1-phosphate, angiotensin II and endothelin-1 signalling [J].
Cho, H ;
Harrison, K ;
Schwartz, O ;
Kehrl, JH .
BIOCHEMICAL JOURNAL, 2003, 371 :973-980
[7]   Involvement of cAMP-response element binding protein-1 in arachidonic acid-induced vascular smooth muscle cell motility [J].
Dronadula, N ;
Rizvi, F ;
Blaskova, E ;
Li, QY ;
Rao, GN .
JOURNAL OF LIPID RESEARCH, 2006, 47 (04) :767-777
[8]   Cyclic AMP-independent activation of protein kinase A by vasoactive peptides [J].
Dulin, NO ;
Niu, JX ;
Browning, DD ;
Ye, RD ;
Voyno-Yasenetskaya, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (24) :20827-20830
[9]   A noncommercial dual luciferase enzyme assay system for reporter gene analysis [J].
Dyer, BW ;
Ferrer, FA ;
Klinedinst, DK ;
Rodriguez, R .
ANALYTICAL BIOCHEMISTRY, 2000, 282 (01) :158-161
[10]   Critical role of cAMP-response element-binding protein for angiotensin II-induced hypertrophy of vascular smooth muscle cells [J].
Funakoshi, Y ;
Ichiki, T ;
Takeda, H ;
Tokuno, T ;
Iino, N ;
Takeshita, A .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (21) :18710-18717