Document Detail


Role of phosphatidylinositol 3-kinase activation in the hypertrophic growth of adult ventricular cardiomyocytes.
MedLine Citation:
PMID:  9876330     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: The present study investigated whether activation of phosphatidylinositol 3-kinase (PI3-kinase) is involved in the stimulation of hypertrophic growth of adult ventricular cardiomyocytes under alpha- or beta-adrenoceptor stimulation. METHODS: Adult ventricular rat cardiomyocytes were used either directly after isolation (day 1 culture) or after cultivation for 6 days in presence of 20% fetal calf serum (day 7 culture). PI3-kinase activity was determined in extracts of cardiomyocytes after immunoprecipitation with an antibody against the p85 subunit of PI3-kinase. The influence of PI3-kinase inhibition on myocardial growth was determined using the specific PI3-kinase inhibitors wortmannin and LY294002. RESULTS: In day 1 cultures alpha-adrenoceptor stimulation, but not beta-adrenoceptor stimulation caused activation of PI3-kinase. In response to alpha-adrenoceptor stimulation but not beta-adrenoceptor stimulation an acceleration of protein synthesis (incorporation of 14C-phenylalanine) and an increase in the total masses of cellular protein and RNA was observed. In these cultures inhibition of PI3-kinase attenuated the acceleration of protein synthesis and the increase in cellular masses of protein or RNA in response to alpha-adrenoceptor stimulation. In day 7 cultures alpha- and beta-adrenoceptor stimulation caused activation of PI3-kinase and increased protein synthesis. In these cultures inhibition of PI3-kinase attenuated the growth response to alpha- and beta-adrenoceptor stimulation. CONCLUSIONS: PI3-kinase activation via protein kinase C-dependent or cAMP-dependent pathways is required for hypertrophic growth of adult cardiomyocytes.
Authors:
K D Schlüter; Y Goldberg; G Taimor; M Schäfer; H M Piper
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cardiovascular research     Volume:  40     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  1998 Oct 
Date Detail:
Created Date:  1999-02-02     Completed Date:  1999-02-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  174-81     Citation Subset:  IM    
Affiliation:
Physiologisches Institut, Universität Giessen, Giessen, Germany. klaus-dieter.schlucter@physiologic.med.uni-giessen.de
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / antagonists & inhibitors,  physiology*
Adrenergic alpha-Agonists / pharmacology
Adrenergic beta-Agonists / pharmacology
Androstadienes / pharmacology
Animals
Cardiomegaly / enzymology*,  metabolism,  pathology
Cells, Cultured
Chromatography, Thin Layer
Chromones / pharmacology
DNA / analysis
Enzyme Activation
Enzyme Inhibitors / pharmacology
Isoproterenol / pharmacology
Male
Morpholines / pharmacology
Myocardium / enzymology,  metabolism,  pathology*
Phenylalanine / metabolism
Phenylephrine / pharmacology
Protein Biosynthesis
RNA / analysis
Rats
Rats, Wistar
Signal Transduction*
Stimulation, Chemical
Time Factors
Uridine / metabolism
Chemical
Reg. No./Substance:
0/Adrenergic alpha-Agonists; 0/Adrenergic beta-Agonists; 0/Androstadienes; 0/Chromones; 0/Enzyme Inhibitors; 0/Morpholines; 154447-36-6/2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; 19545-26-7/wortmannin; 58-96-8/Uridine; 59-42-7/Phenylephrine; 63-91-2/Phenylalanine; 63231-63-0/RNA; 7683-59-2/Isoproterenol; 9007-49-2/DNA; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase

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


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