Induction of tenascin-C in cardiac myocytes by mechanical deformation. Role of reactive oxygen species

• Published in: The Journal of biological chemistry Vol. 274; no. 31; pp. 21840 - 21846
• Main Authors: Yamamoto, K, Dang, Q N, Kennedy, S P, Osathanondh, R, Kelly, R A, Lee, R T
• Format: Journal Article
• Language: English
• Published: United States 30-07-1999
• Subjects: 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt - pharmacology; Acetylcysteine - pharmacology; Alternative Splicing; Angiotensin Receptor Antagonists; Animals; Animals, Newborn; Antioxidants - pharmacology; Catalase - pharmacology; Cells, Cultured; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Fibronectins - genetics; Gene Expression Regulation - drug effects; Genes, Reporter; Heart Ventricles; I-kappa B Kinase; I-kappa B Proteins; Indazoles - pharmacology; Myocardium - cytology; Myocardium - metabolism; NF-KappaB Inhibitor alpha; Osteonectin - genetics; Promoter Regions, Genetic; Protein Isoforms - genetics; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; RNA, Messenger - genetics; Stress, Mechanical; Tenascin - biosynthesis; Tenascin - genetics; Transcription, Genetic - drug effects; Transfection
• ISSN: 0021-9258
• DOI: 10.1074/jbc.274.31.21840

Mechanical overload may change cardiac structure through angiotensin II-dependent and angiotensin II-independent mechanisms. We investigated the effects of mechanical strain on the gene expression of tenascin-C, a prominent extracellular molecule in actively remodeling tissues, in neonatal rat cardiac myocytes. Mechanical strain induced tenascin-C mRNA (3.9 +/- 0.5-fold, p < 0.01, n = 13) and tenascin-C protein in an amplitude-dependent manner but did not induce secreted protein acidic and rich in cysteine nor fibronectin. RNase protection assay demonstrated that mechanical strain induced all three alternatively spliced isoforms of tenascin-C. An angiotensin II receptor type 1 antagonist inhibited mechanical induction of brain natriuretic peptide but not tenascin-C. Antioxidants such as N-acetyl-L-cysteine, catalase, and 1, 2-dihydroxy-benzene-3,5-disulfonate significantly inhibited induction of tenascin-C. Truncated tenascin-C promoter-reporter assays using dominant negative mutants of IkappaBalpha and IkappaB kinase beta and electrophoretic mobility shift assays indicated that mechanical strain increases tenascin-C gene transcription by activating nuclear factor-kappaB through reactive oxygen species. Our findings demonstrate that mechanical strain induces tenascin-C in cardiac myocytes through a nuclear factor-kappaB-dependent and angiotensin II-independent mechanism. These data also suggest that reactive oxygen species may participate in mechanically induced left ventricular remodeling.