Angiotensin II Induces Nuclear Factor- κ B Activation in Cultured Neonatal Rat Cardiomyocytes Through Protein Kinase C Signaling Pathway

doi:10.1006/jmcc.2000.1211

Journal of Molecular and Cellular Cardiology

Volume 32, Issue 10, October 2000, Pages 1767-1778

https://doi.org/10.1006/jmcc.2000.1211 Get rights and content

Abstract

Rat neonatal ventricular cardiomyocytes (RNVM) possess G protein-coupled AT₁receptors for angiotensin II (AngII) that activate multiple intracellular pathways. To elucidate potential signaling mechanisms involved, we focussed on the nuclear transcription factor-kappa B (NF- κ B) in RNVM culture. Using specific antibody to NF-κ Bp65, immunolocalization of NF- κ B was cytoplasmic in unstimulated cardiomyocytes, whereas NF-κ B was translocated into the RNVM nucleus in response to AngII. This translocation was inhibited in the presence of calphostin C, a specific inhibitor of protein kinase C (PKC). Western blot analysis showed an increase of NF- κ B in AngII-stimulated cardiomyocyte nuclear extracts as compared to controls. Biomolecular interaction analysis (BIA analysis) of NF-κ B activation showed that only AngII-nuclear extracts bound to NF- κ B consensus sequence with a high degree of affinity. This DNA-binding capacity was completely lost in calphostin C-treated cells. At transcriptional level in RNVM, AngII mediates the upregulation of matrix gelatinase (MMP-9), which is totally inhibited by calphostin C treatment. In conclusion, cardiomyocyte nuclear NF- κ B translocation in response to Ang II via PKC pathway activates cardiomyocyte-specific transcription of MMP-9 and may activate transcription from responsive genes which are involved in cardiac hypertrophy process and/or cardiac remodeling.

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^f1: Please address all correspondence to: Patricia Rouet-Benzineb, INSERM U 492/Faculté de Médecine, 8, rue du Général Sarrail, 94010 CRETEIL Cedex, France. E-mail: [email protected]

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Regular ArticleAngiotensin II Induces Nuclear Factor- κ B Activation in Cultured Neonatal Rat Cardiomyocytes Through Protein Kinase C Signaling Pathway

Abstract

J Mol Cell Cardiol

Curr Opinion Cell Biol

Immunol Today

J Biol Chem

Anal Biochem

Methods Enzymol

Biochem Biophysic Res Comm

Cardiac hypertrophy: mechanical, neural, and endocrine dependence

Circulation

Cellular mechanism of cardiac hypertrophy

Br Heart J

Mechanical stretch induces enhanced expression of angiotensin II receptor subtypes in neonatal rat cardiac myocytes

Circ Res

Molecular mechanisms of angiotensin II in modulating cardiac function: intracardiac effects and signal transduction pathways

J Mol Cell Cardiol

Molecular characterization of angiotensin II-induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts: a critical role of the AT1 receptor subtype

Circ Res

Regular Article
Angiotensin II Induces Nuclear Factor- κ B Activation in Cultured Neonatal Rat Cardiomyocytes Through Protein Kinase C Signaling Pathway