Document Detail

Dominant negative mutant of c-Jun inhibits cardiomyocyte hypertrophy induced by endothelin 1 and phenylephrine.
MedLine Citation:
PMID:  11799083     Owner:  NLM     Status:  MEDLINE    
The activator protein 1 (AP-1) transcriptional complex, containing Jun and Fos proteins, is involved in regulating many cellular processes such as proliferation and differentiation. However, little is known about a direct relationship between AP-1 activities and cardiomyocyte hypertrophy. To elucidate the roles of myocardial AP-1 activities, dominant negative mutant of c-Jun (DNJun) was overexpressed in cultured rat neonatal ventricular myocytes by adenovirus vector to abrogate endogenous AP-1 activation. Cardiomyocytes were treated with 100 nmol/L endothelin 1 (ET) and 10 micromol/L phenylephrine (PE) to induce myocardial cell hypertrophy. Both ET and PE significantly enhanced AP-1 DNA binding activities (3.4-fold by ET and 4.8-fold by PE at 3 hours, P<0.01). At 48 hours after stimulation, ET and PE significantly increased incorporation of (3)H-phenylalanine (1.4-fold by ET and 1.5-fold by PE, P<0.01), cell size (2.3-fold and 2.5-fold, P<0.01), and mRNA expression of atrial natriuretic peptide (ANP; 1.9-fold and 1.8-fold, P<0.01) and brain natriuretic peptide (BNP; 1.6-fold and 1.6-fold, P<0.01). Adenovirus carrying DNJun prevented the transcriptional activation of the AP-1 by ET and PE, using AP-1 reporter enzyme firefly luciferase assay. Moreover, DNJun prevented the increase in incorporation of (3)H-phenylalanine, cell size, and the mRNA expression of ANP and BNP by ET and PE. In conclusion, we provide the first evidence that DNJun inhibits cardiomyocyte hypertrophy through inhibition of AP-1 transcriptional activity.
Takashi Omura; Minoru Yoshiyama; Ken Yoshida; Yasuhiro Nakamura; Shokei Kim; Hiroshi Iwao; Kazuhide Takeuchi; Junichi Yoshikawa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Hypertension     Volume:  39     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2002 Jan 
Date Detail:
Created Date:  2002-01-18     Completed Date:  2002-02-20     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  81-6     Citation Subset:  IM    
Department of Internal Medicine and Cardiology, Osaka City University Medical School, Osaka, Japan.
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MeSH Terms
Adenoviridae / genetics
Atrial Natriuretic Factor / biosynthesis
Cardiomegaly / chemically induced,  genetics*,  metabolism,  prevention & control
Cell Size / drug effects
Cells, Cultured
DNA, Complementary / genetics,  metabolism
Endothelin-1 / antagonists & inhibitors*,  pharmacology
Genes, Dominant / genetics
Genes, jun / genetics*
Heart Ventricles / cytology,  drug effects,  metabolism
Lac Operon / genetics
Myocardium / metabolism
Natriuretic Peptide, Brain / biosynthesis
Phenylephrine / antagonists & inhibitors*,  pharmacology
Proto-Oncogene Proteins c-jun / biosynthesis,  genetics
Rats, Wistar
Transcription Factor AP-1 / antagonists & inhibitors,  metabolism
Transcriptional Activation / genetics
Reg. No./Substance:
0/DNA, Complementary; 0/Endothelin-1; 0/Proto-Oncogene Proteins c-jun; 0/Transcription Factor AP-1; 114471-18-0/Natriuretic Peptide, Brain; 59-42-7/Phenylephrine; 85637-73-6/Atrial Natriuretic Factor

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