MolPharm

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ishida, A.
Right arrow Articles by Abumiya, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ishida, A.
Right arrow Articles by Abumiya, T.

Vol. 56, Issue 5, 938-946, November 1999

Tumor Suppressor p53 But Not cGMP Mediates NO-Induced Expression of p21Waf1/Cip1/Sdi1 in Vascular Smooth Muscle Cells

Akio Ishida, Toshiyuki Sasaguri, Yoshikazu Miwa, Chiya Kosaka, Yoji Taba, and Takeo Abumiya

Departments of Bioscience (A.I., T.S., Y.M., Y.T.) and Epidemiology (T.A.), National Cardiovascular Center Research Institute; Third Department of Internal Medicine (A.I., Y.T.), University of the Ryukyus School of Medicine; Second Department of Internal Medicine (Y.M.), Faculty of Medicine, Kyushu University; and Department of Clinical Sciences and Laboratory Medicine (C.K.), Kansai Medical University, Osaka, Japan

Cyclin-dependent kinase inhibitor p21Waf1/Cip1/Sdi1 has been suggested to be involved in the antiproliferative effect of nitric oxide (NO) in vascular smooth muscle cells (VSMCs). To elucidate the mechanism underlying NO-induced p21 expression, we investigated the roles of tumor suppressor p53 and the guanylate cyclase-cGMP pathway. The induction of p21 by the NO donor S-nitroso-N-acetylpenicillamine (SNAP) seemed to be due to transactivation because SNAP elevated the activity of p21 promoter but did not stabilize p21 mRNA and protein. Because SNAP did not stimulate the deletion mutant of p21 promoter that lacked p53 binding sites, we tested the involvement of p53. The expression level of p53 was down-regulated after mitogenic stimulation, whereas it was sustained in the presence of SNAP. SNAP markedly stimulated DNA binding activity of p53. Furthermore, SNAP failed to induce p21 in VSMCs obtained from p53-knock out mice and in A431 cells that contained mutated p53. The antiproliferative effect of SNAP also was attenuated in these cells. NO stimulates guanylate cyclase and its product cGMP has been shown to inhibit VSMC proliferation. However, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a guanylate cyclase inhibitor, did not prevent SNAP-induced p21 expression. 8-Bromo-cGMP, 3-isobutyl-1-methylxanthine, and their combination did not induce p21. Although 8-bromo-cGMP had a small antiproliferative effect, the elevation of cGMP concentration induced by SNAP was little throughout the G1 phase. The antiproliferative effect of SNAP was not attenuated by Rp-8-bromoguanosine-3',5'-monophosphorothioate, an inhibitor of cGMP-dependent protein kinase. These results suggested that NO induces p21 through a p53-dependent but cGMP-independent pathway.

Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
J. Zhang, S. Wang, S. Kern, X. Cui, and R. L. Danner
Nitric Oxide Down-regulates Polo-like Kinase 1 through a Proximal Promoter Cell Cycle Gene Homology Region
J. Biol. Chem., January 12, 2007; 282(2): 1003 - 1009.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
M. Miyagi, Y. Miwa, F. Takahashi-Yanaga, S. Morimoto, and T. Sasaguri
Activator Protein-1 Mediates Shear Stress-Induced Prostaglandin D Synthase Gene Expression in Vascular Endothelial Cells
Arterioscler. Thromb. Vasc. Biol., May 1, 2005; 25(5): 970 - 975.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
S. Mizuno, M. Kadowaki, Y. Demura, S. Ameshima, I. Miyamori, and T. Ishizaki
p42/44 Mitogen-Activated Protein Kinase Regulated by p53 and Nitric Oxide in Human Pulmonary Arterial Smooth Muscle Cells
Am. J. Respir. Cell Mol. Biol., August 1, 2004; 31(2): 184 - 192.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
F. M. D'Souza, R. L. Sparks, H. Chen, P. J. Kadowitz, and J. R. Jeter Jr.
Mechanism of eNOS gene transfer inhibition of vascular smooth muscle cell proliferation
Am J Physiol Cell Physiol, January 1, 2003; 284(1): C191 - C199.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
T. Abumiya, T. Sasaguri, Y. Taba, Y. Miwa, and M. Miyagi
Shear Stress Induces Expression of Vascular Endothelial Growth Factor Receptor Flk-1/KDR Through the CT-Rich Sp1 Binding Site
Arterioscler. Thromb. Vasc. Biol., June 1, 2002; 22(6): 907 - 913.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
P. M. Bauer, G. M. Buga, and L. J. Ignarro
Role of p42/p44 mitogen-activated-protein kinase and p21waf1/cip1 in the regulation of vascular smooth muscle cell proliferation by nitric oxide
PNAS, October 5, 2001; (2001) 211443198.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
Y. Miwa, T. Sasaguri, H. Inoue, Y. Taba, A. Ishida, and T. Abumiya
15-Deoxy-Delta 12,14-prostaglandin J2 Induces G1 Arrest and Differentiation Marker Expression in Vascular Smooth Muscle Cells
Mol. Pharmacol., October 1, 2000; 58(4): 837 - 844.
[Abstract] [Full Text]

Home page
 Circ. Res.Home page
Y. Taba, T. Sasaguri, M. Miyagi, T. Abumiya, Y. Miwa, T. Ikeda, and M. Mitsumata
Fluid Shear Stress Induces Lipocalin-Type Prostaglandin D2 Synthase Expression in Vascular Endothelial Cells
Circ. Res., May 12, 2000; 86(9): 967 - 973.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
D. Champlin and J. Truman
Ecdysteroid coordinates optic lobe neurogenesis via a nitric oxide signaling pathway
Development, January 8, 2000; 127(16): 3543 - 3551.
[Abstract] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
P. M. Bauer, G. M. Buga, and L. J. Ignarro
Role of p42/p44 mitogen-activated-protein kinase and p21waf1/cip1 in the regulation of vascular smooth muscle cell proliferation by nitric oxide
PNAS, October 23, 2001; 98(22): 12802 - 12807.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1999 by the American Society for Pharmacology and Experimental Therapeutics