Heparin Responses in Vascular Smooth Muscle Cells Involve cGMP-Dependent Protein Kinase (PKG)

被引:23
作者
Gilotti, Albert C. [1 ]
Nimlamool, Wutigri [1 ]
Pugh, Raymond [2 ]
Slee, Joshua B. [1 ]
Barthol, Trista C. [1 ]
Miller, Elizabeth A. [1 ]
Lowe-Krentz, Linda J. [1 ]
机构
[1] Lehigh Univ, Dept Biol Sci, Bethlehem, PA 18015 USA
[2] Lehigh Univ, Dept Chem, Bethlehem, PA 18015 USA
关键词
CYCLIC-GMP; NITRIC-OXIDE; ENDOTHELIAL-CELLS; UP-REGULATION; EXPRESSION; PROLIFERATION; ACTIVATION; INHIBITION; PHOSPHATASE; PDGF;
D O I
10.1002/jcp.24677
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Published data provide strong evidence that heparin treatment of proliferating vascular smooth muscle cells results in decreased signaling through the ERK pathway and decreases in cell proliferation. In addition, these changes have been shown to be mimicked by antibodies that block heparin binding to the cell surface. Here, we provide evidence that the activity of protein kinase G is required for these heparin effects. Specifically, a chemical inhibitor of protein kinase G, Rp-8-pCPT-cGMS, eliminates heparin and anti-heparin receptor antibody effects on bromodeoxyuridine incorporation into growth factor-stimulated cells. In addition, protein kinase G inhibitors decrease heparin effects on ERK activity, phosphorylation of the transcription factor Elk-1, and heparin-induced MKP-1 synthesis. Although transient, the levels of cGMP increase in heparin treated cells. Finally, knock down of protein kinase G also significantly decreases heparin effects in growth factor-activated vascular smooth muscle cells. Together, these data indicate that heparin effects on vascular smooth muscle cell proliferation depend, at least in part, on signaling through protein kinase G. J. Cell. Physiol. 229: 2142-2152, 2014. (c) 2014 Wiley Periodicals, Inc.
引用
收藏
页码:2142 / 2152
页数:11
相关论文
共 49 条
[1]   Atrial natriuretic factor inhibits mitogen-induced growth in aortic smooth muscle cells [J].
Baldini, PM ;
De Vito, P ;
Fraziano, M ;
Mattioli, P ;
Luly, P ;
Di Nardo, P .
JOURNAL OF CELLULAR PHYSIOLOGY, 2002, 193 (01) :103-109
[2]   Vascular smooth muscle cell growth and insulin regulation of mitogen-activated protein kinase in hypertension [J].
Begum, N ;
Song, Y ;
Rienzie, J ;
Ragolia, L .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 1998, 275 (01) :C42-C49
[3]   Heparin Treatment of Vascular Smooth Muscle Cells Results in the Synthesis of the Dual-Specificity Phosphatase MKP-1 [J].
Blaukovitch, Cheryl Isleib ;
Pugh, Raymond ;
Gilotti, Albert C. ;
Kanyi, Daniela ;
Lowe-Krentz, Linda J. .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2010, 110 (02) :382-391
[4]   Nuclear translocation of p42/p44 mitogen-activated protein kinase is required for growth factor-induced gene expression and cell cycle entry [J].
Brunet, A ;
Roux, D ;
Lenormand, P ;
Dowd, S ;
Keyse, S ;
Pouysségur, J .
EMBO JOURNAL, 1999, 18 (03) :664-674
[5]   BINDING AND INTERNALIZATION OF HEPARIN BY VASCULAR SMOOTH-MUSCLE CELLS [J].
CASTELLOT, JJ ;
WONG, K ;
HERMAN, B ;
HOOVER, RL ;
ALBERTINI, DF ;
WRIGHT, TC ;
CALEB, BL ;
KARNOVSKY, MJ .
JOURNAL OF CELLULAR PHYSIOLOGY, 1985, 124 (01) :13-20
[6]   HEPARIN SELECTIVELY INHIBITS A PROTEIN-KINASE C-DEPENDENT MECHANISM OF CELL-CYCLE PROGRESSION IN CALF AORTIC SMOOTH-MUSCLE CELLS [J].
CASTELLOT, JJ ;
PUKAC, LA ;
CALEB, BL ;
WRIGHT, TC ;
KARNOVSKY, MJ .
JOURNAL OF CELL BIOLOGY, 1989, 109 (06) :3147-3155
[7]   CULTURED ENDOTHELIAL-CELLS PRODUCE A HEPARIN-LIKE INHIBITOR OF SMOOTH-MUSCLE CELL-GROWTH [J].
CASTELLOT, JJ ;
ADDONIZIO, ML ;
ROSENBERG, R ;
KARNOVSKY, MJ .
JOURNAL OF CELL BIOLOGY, 1981, 90 (02) :372-379
[8]   Evidence for the existence of a constitutive nitric oxide synthase in vascular smooth muscle [J].
Cheah, LS ;
Gwee, MCE ;
Das, R ;
Ballard, H ;
Yang, YF ;
Daniel, EE ;
Kwan, CY .
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 2002, 29 (08) :725-727
[9]   Inhibition of TRPC1/TRPC3 by PKG contributes to NO-mediated vasorelaxation [J].
Chen, Jie ;
Crossland, Randy F. ;
Noorani, Muzamil M. Z. ;
Marrelli, Sean P. .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2009, 297 (01) :H417-H424
[10]   cGMP-dependent protein kinase and the regulation of vascular smooth muscle cell gene expression: possible involvement of Elk-1 sumoylation [J].
Choi, ChungSik ;
Sellak, Hassan ;
Brown, Felricia M. ;
Lincoln, Thomas M. .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2010, 299 (05) :H1660-H1670