In:
Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 39, No. 1 ( 2002-01), p. 81-86
Abstract:
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 μmol/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.
Type of Medium:
Online Resource
ISSN:
0194-911X
,
1524-4563
DOI:
10.1161/hy0102.100783
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2002
detail.hit.zdb_id:
2094210-2
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