Document Detail

Nitric oxide-induced downregulation of Cdk2 activity and cyclin A gene transcription in vascular smooth muscle cells.
MedLine Citation:
PMID:  9610538     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Nitric oxide (NO) inhibits vascular smooth muscle cell (VSMC) proliferation and neointima formation after balloon injury. However, the molecular mechanisms underlying NO-mediated growth arrest are poorly understood. In the present study, we examined the effects of the NO donors sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP) on cell cycle activity in VSMCs.
METHODS AND RESULTS: Stimulation of quiescent rat VSMCs with serum leads to an increase in cyclin-dependent kinase (cdk)2 kinase activity that correlates with a marked induction of cyclin A protein expression. The addition of SNP or SNAP to VSMC cultures at the time of serum stimulation abrogates the induction of cdk2 activity without suppressing protein levels of cdk2 or cyclin E. These NO donors block serum-stimulated upregulation of cyclin A mRNA and protein and repress the serum induction of cyclin A promoter activity in VSMCs.
CONCLUSIONS: The addition of the nitric oxide donors SNP or SNAP to mitogen-stimulated VSMCs prevents activation of cdk2, a key regulator of the G1 and S phases of the cell cycle. These NO donors do not affect the expression of cdk2 protein but block the mitogen-induced expression of cyclin A, an activating subunit of cdk2. SNP and SNAP also repress the mitogen-stimulated activation of the cyclin A promoter. These data suggest that the antiproliferative effect of NO on VSMCs results, at least in part, from the repression of cyclin A gene transcription.
K Guo; V Andrés; K Walsh
Related Documents :
20332458 - Cadpe suppresses cyclin d1 expression in hepatocellular carcinoma by blocking il-6-indu...
14517308 - Tor regulates the subcellular localization of ime1, a transcriptional activator of meio...
9664138 - Genistein-induced g2/m arrest is associated with the inhibition of cyclin b1 and the in...
8815878 - P53-independent cyclin g expression in a group of mature neurons and its enhanced expre...
24895988 - Microrna-222 promotes the proliferation and migration of cervical cancer cells.
15083518 - Keratin 14 cre transgenic mice authenticate keratin 14 as an oocyte-expressed protein.
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  97     ISSN:  0009-7322     ISO Abbreviation:  Circulation     Publication Date:  1998 May 
Date Detail:
Created Date:  1998-06-11     Completed Date:  1998-06-11     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2066-72     Citation Subset:  AIM; IM    
Division of Cardiovascular Research, St Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Mass 02135-2997, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
CDC2-CDC28 Kinases*
Cyclin A / genetics*
Cyclin-Dependent Kinase 2
Cyclin-Dependent Kinases / metabolism*
Muscle, Smooth, Vascular / metabolism*
Nitric Oxide / physiology*
Nitroprusside / pharmacology
Penicillamine / analogs & derivatives,  pharmacology
Promoter Regions, Genetic
Protein-Serine-Threonine Kinases / metabolism*
Transcription, Genetic
Grant Support
Reg. No./Substance:
0/Cyclin A; 0/S-nitro-N-acetylpenicillamine; 10102-43-9/Nitric Oxide; 15078-28-1/Nitroprusside; 52-67-5/Penicillamine; EC Kinases; EC Kinases; EC protein, rat; EC Kinase 2; EC Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Exacerbated transplant arteriosclerosis in inducible nitric oxide-deficient mice.
Next Document:  Influence of phase duration of biphasic waveforms on defibrillation energy requirements with a 70-mi...