| Polyamines, NO and cGMP mediate stimulation of DNA synthesis by tumor necrosis factor and lipopolysaccharide in chick embryo cardiomyocytes. | |
| | |
MedLine Citation:
|
PMID: 11164851 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
OBJECTIVE: We have recently shown that tumor necrosis factor-alpha (TNFalpha) and lipopolysaccharide (LPS) stimulate DNA synthesis in chick embryo cardiomyocytes (CMs). The aim of the present research was to investigate the pathways involved in this mitogenic response. METHODS: CMs were isolated from 10-day-old chick embryos and grown to confluence. After 20 h of serum starvation the cells were treated with TNFalpha and LPS, and/or specific agonists and antagonists to manipulate the levels of polyamines, NO, cGMP and their biosynthetic enzymes ornithine decarboxylase (ODC), nitric oxide synthase (NOS) and soluble guanylate cyclase (sGC). ODC, NOS, sGC activities and cGMP contents were determined by radiochemical procedures. DNA synthesis was determined by incorporation of [3H]-thymidine. RESULTS: Treatment of CMs with TNFalpha and LPS increased cell number and [3H]-thymidine incorporation. Addition of TNFalpha and LPS provoked an induction of ODC, with consequent polyamine accumulation, and a more delayed enhancement of NOS activity, which appeared to be independent of the activation of the ODC-polyamine system. TNFalpha and LPS treatment also enhanced cGMP level in CMs and both polyamine and NO biosyntheses appeared to be required. Experiments with specific inhibitors of ODC and NOS, as well as with inhibitors of sGC and cGMP-dependent protein kinase (PKG), showed that polyamine-, NO- and cGMP-dependent pathways are required for the mitogenic action of TNFalpha and LPS. Moreover, addition of exogenous polyamines to untreated cells raised the cGMP level in a NO-dependent fashion, and enhanced [3H]-thymidine incorporation. The latter effect was inhibited by sGC or PKG inhibitors. Treatment of quiescent cells with NO donors, 8-bromo-cGMP or YC-1, an sGC activator, also promoted DNA synthesis. Furthermore, putrescine and NO donor can additively activate sGC in cell-free extracts. CONCLUSION: TNFalpha and LPS stimulate DNA synthesis in chick embryo CMs and this effect is mediated by polyamines, NO and intracellular cGMP. |
| | |
Authors:
|
B Tantini; F Flamigni; C Pignatti; C Stefanelli; M Fattori; A Facchini; E Giordano; C Clô; C M Caldarera |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Cardiovascular research Volume: 49 ISSN: 0008-6363 ISO Abbreviation: Cardiovasc. Res. Publication Date: 2001 Feb |
Date Detail:
|
Created Date: 2001-02-22 Completed Date: 2001-04-12 Revised Date: 2006-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: Netherlands |
Other Details:
|
Languages: eng Pagination: 408-16 Citation Subset: IM |
Affiliation:
|
Department of Biochemistry "G.Moruzzi", School of Medicine, University of Bologna, via Irnerio, 48 40126, Bologna, Italy. tantini@biocfarm.unibo.it |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Alkaloids
/
pharmacology Aminoquinolines / pharmacology Animals Carbazoles* Cells, Cultured Chick Embryo Cyclic GMP / metabolism* DNA / biosynthesis* Eflornithine / pharmacology Enzyme Activation Enzyme Inhibitors / pharmacology Guanylate Cyclase / antagonists & inhibitors, metabolism Indoles* Lipopolysaccharides / pharmacology Methylene Blue / pharmacology Myocardium / metabolism* Nitric Oxide / metabolism* Nitric Oxide Synthase / antagonists & inhibitors, metabolism Ornithine Decarboxylase / antagonists & inhibitors, metabolism Polyamines / metabolism* Protein Kinase Inhibitors Stimulation, Chemical Tumor Necrosis Factor-alpha / pharmacology omega-N-Methylarginine / pharmacology |
| Chemical | |
Reg. No./Substance:
|
0/Alkaloids; 0/Aminoquinolines; 0/Carbazoles; 0/Enzyme Inhibitors; 0/Indoles; 0/Lipopolysaccharides; 0/Polyamines; 0/Protein Kinase Inhibitors; 0/Tumor Necrosis Factor-alpha; 10102-43-9/Nitric Oxide; 126643-37-6/KT 5823; 17035-90-4/omega-N-Methylarginine; 61-73-4/Methylene Blue; 70052-12-9/Eflornithine; 7665-99-8/Cyclic GMP; 9007-49-2/DNA; 91300-60-6/6-anilino-5,8-quinolinedione; EC 1.14.13.39/Nitric Oxide Synthase; EC 4.1.1.17/Ornithine Decarboxylase; EC 4.6.1.2/Guanylate Cyclase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Mouse model of myocardial remodelling after ischemia: role of intercellular adhesion molecule-1.
Next Document: Molecular characterization of the ventricular conduction system in the developing mouse heart: topog...