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    
Abstract/OtherAbstract:
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.
Authors:
K Guo; V Andrés; K Walsh
Related Documents :
10066068 - Cyclin d1 in breast cancer.
12221098 - Increased hepatic forkhead box m1b (foxm1b) levels in old-aged mice stimulated liver re...
15659578 - Conserved and specific functions of mammalian ssu72.
17404108 - Menatetrenone, a vitamin k2 analogue, inhibits hepatocellular carcinoma cell growth by ...
12390528 - Adenosine a(2a) receptor-mediated inhibition of rod opsin mrna expression in tiger sala...
21965718 - Ebp1 inhibits translation of androgen receptor mrna in castration resistant prostate ca...
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    
Affiliation:
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
Descriptor/Qualifier:
Animals
CDC2-CDC28 Kinases*
Cyclin A / genetics*
Cyclin-Dependent Kinase 2
Cyclin-Dependent Kinases / metabolism*
Down-Regulation
Muscle, Smooth, Vascular / metabolism*
Nitric Oxide / physiology*
Nitroprusside / pharmacology
Penicillamine / analogs & derivatives,  pharmacology
Promoter Regions, Genetic
Protein-Serine-Threonine Kinases / metabolism*
Rats
Transcription, Genetic
Grant Support
ID/Acronym/Agency:
AR-40197/AR/NIAMS NIH HHS; HL-50692/HL/NHLBI NIH HHS
Chemical
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 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.22/CDC2-CDC28 Kinases; EC 2.7.11.22/Cdk2 protein, rat; EC 2.7.11.22/Cyclin-Dependent Kinase 2; EC 2.7.11.22/Cyclin-Dependent 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...