Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-6-10
pubmed:abstractText
NO and cGMP have antigrowth and anti-inflammatory effects on the vessel wall in response to injury. It is well established that after vascular injury proinflammatory cytokines are involved in vascular wall remodeling. The purpose of this study was to ascertain the signaling mechanisms involved in cGMP-dependent protein kinase (PKG) suppression by inflammatory cytokines in primary bovine aortic vascular smooth muscle cells (VSMC). Interleukin (IL)-Ibeta, tumor necrosis factor (TNF)-alpha, and LPS decreased the mRNA and protein levels of PKG in VSMC. IL-Ibeta, TNF-alpha, and LPS increased inducible nitric oxide synthase (iNOS) expression and cGMP production. Treatment of cells with selective inhibitors of iNOS or soluble guanylate cyclase (sGC) reversed the downregulation of PKG expression induced by cytokines and LPS. The NO donor (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA NONOate) and 3-(5-hydroxymethyl-2-furyl)-1-benzylindazole (YC-1), a NO-independent sGC activator, decreased PKG mRNA and protein expression in bovine aortic VSMC. Cyclic nucleotide analogs [8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate (CPT-cGMP) and 8-(4-chlorophenylthio)adenosine 3,5'-cyclic monophosphate (CPT-cAMP)] also suppressed PKG mRNA and protein expression. However, CPT-cAMP was more effective than CPT-cGMP in decreasing PKG mRNA levels. Selective inhibition of PKA with the Rp isomer of 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphorothioate (Rp-8p-CPT cAMPS) prevented the downregulation of PKG by LPS. In contrast, the Rp isomer of 8-(4-chlorophenylthio)guanosine 3,5'-cyclic monophosphorothioate (Rp-8p-CPT cGMPS; inhibitor of PKG) had no effect on LPS-induced inhibition of PKG mRNA and protein expression. These studies suggest that cross-activation of PKA in response to iNOS expression by inflammatory mediators downregulates PKG expression in bovine aortic VSMC.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/1H-(1,2,4)oxadiazolo(4,3-a)quinoxali..., http://linkedlifedata.com/resource/pubmed/chemical/2,2'-(hydroxynitrosohydrazono)bis-et..., http://linkedlifedata.com/resource/pubmed/chemical/3-(5'-hydroxymethyl-2'-furyl)-1-benz..., http://linkedlifedata.com/resource/pubmed/chemical/Cyclic GMP-Dependent Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Activators, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Indazoles, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1, http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides, http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Donors, http://linkedlifedata.com/resource/pubmed/chemical/Nitroso Compounds, http://linkedlifedata.com/resource/pubmed/chemical/Nucleotides, Cyclic, http://linkedlifedata.com/resource/pubmed/chemical/Oxadiazoles, http://linkedlifedata.com/resource/pubmed/chemical/Quinoxalines, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0363-6143
pubmed:author
pubmed:issnType
Print
pubmed:volume
287
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
C88-96
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:14985234-Animals, pubmed-meshheading:14985234-Aorta, pubmed-meshheading:14985234-Cattle, pubmed-meshheading:14985234-Cells, Cultured, pubmed-meshheading:14985234-Cyclic GMP-Dependent Protein Kinases, pubmed-meshheading:14985234-Down-Regulation, pubmed-meshheading:14985234-Enzyme Activators, pubmed-meshheading:14985234-Enzyme Inhibitors, pubmed-meshheading:14985234-Humans, pubmed-meshheading:14985234-Indazoles, pubmed-meshheading:14985234-Interleukin-1, pubmed-meshheading:14985234-Lipopolysaccharides, pubmed-meshheading:14985234-Muscle, Smooth, Vascular, pubmed-meshheading:14985234-Myocytes, Smooth Muscle, pubmed-meshheading:14985234-Nitric Oxide Donors, pubmed-meshheading:14985234-Nitroso Compounds, pubmed-meshheading:14985234-Nucleotides, Cyclic, pubmed-meshheading:14985234-Oxadiazoles, pubmed-meshheading:14985234-Quinoxalines, pubmed-meshheading:14985234-Recombinant Proteins, pubmed-meshheading:14985234-Tumor Necrosis Factor-alpha
pubmed:year
2004
pubmed:articleTitle
Downregulation of cGMP-dependent protein kinase expression by inflammatory cytokines in vascular smooth muscle cells.
pubmed:affiliation
Department of Physiology, University of South Alabama, Mobile, AL 36688, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.