Signaling mechanisms underlying strain-dependent brain natriuretic peptide gene transcription

• Published in: Canadian journal of physiology and pharmacology Vol. 79; no. 8; pp. 640 - 645
• Main Authors: Liang, Faquan, Kovacic-Milivojevic, Branka, Chen, Songcang, Cui, Junfeng, Roediger, Fred, Intengan, Hope, Gardner, David G
• Format: Journal Article
• Language: English
• Published: Ottawa, Canada NRC Research Press 01.08.2001; National Research Council of Canada; Canadian Science Publishing NRC Research Press
• Subjects: Animals; beta-Galactosidase - biosynthesis; beta-Galactosidase - genetics; Biological and medical sciences; Carrier Proteins - metabolism; Cells, Cultured; Fundamental and applied biological sciences. Psychology; Genetics; Heart; Heart disease; Integrins - genetics; JNK Mitogen-Activated Protein Kinases; Luciferases - biosynthesis; Luciferases - genetics; MAP Kinase Kinase 4; Mitogen-Activated Protein Kinase Kinases - metabolism; Mitogen-Activated Protein Kinases - biosynthesis; Mitogen-Activated Protein Kinases - genetics; Mitogen-Activated Protein Kinases - metabolism; Myocardium - cytology; Myocardium - metabolism; Natriuretic Peptide, Brain - biosynthesis; Natriuretic Peptide, Brain - genetics; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Peptides; Plasmids; Precipitin Tests; Rats; Signal Transduction - genetics; Signal Transduction - physiology; Stress, Mechanical; Transcription, Genetic - genetics; Transfection; Vertebrates: cardiovascular system; Heart; Brain natriuretic peptide; Rat; Transcription; Enzyme; Transferases; Rodentia; Heart ventricle; Activation; In vitro; Myocyte; Biomechanics; Signal transduction; Vertebrata; Mammalia; Integrin; Mechanical stress; Protein kinase; Newborn animal; Circulatory system
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/y01-036

Activation of brain natriuretic peptide (BNP) gene promoter activity represents one of the earliest and most reliable markers of ventricular cardiac myocyte hypertrophy. We recently demonstrated that mechanical strain increases immunoreactive BNP secretion, steady-state BNP mRNA levels and BNP gene transcriptional activity in neonatal rat myocyte cultures. We have also shown that strain-dependent BNP gene transcription is critically dependent on the functional integrity of a number of integrins (specfically β1, β3, and αv β5 integrins) present on the surface of cardiac myocytes. When used alone, each of these antibodies resulted in a significant reduction in strain-dependent activation of a transfected hBNP-luciferase reporter and inhibition of a number of signaling pathways that have been linked to stimulation of this reporter (e.g., extracellular signal regulated kinase and c-Jun amino terminal kinase). The present study shows that combinations of these antibodies resulted in further reductions in hBNP gene promoter activity and inhibition of the relevant signaling cascades. These studies provide further support for the importance of integrin-matrix interactions in promoting strain-dependent changes in cardiac myocyte gene transcription.Key words: mechanical strain, brain natriuretic peptide, integrins, mitogen-activated protein kinase, cardiac myocyte.