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

Mechanical overload may change cardiac structure through angiotensin II-dep endent and angiotensin II-independent mechanisms. We investigated the effec ts of mechanical strain on the gene expression of tenascin-C, a prominent e xtracellular molecule in actively remodeling tissues, in neonatal rat cardi ac 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 bu t did not induce secreted protein acidic and rich in cysteine nor fibronect in, RNase protection assay demonstrated that mechanical strain induced all three alternatively spliced isoforms of tenascin-C, An angiotensin II recep tor type 1 antagonist inhibited mechanical induction of brain natriuretic p eptide but not tenascin-C. Antioxidants such as N-acetyl-L-cysteine, catala se, and 1,2-dihydroxy-benzene-3,5-disulfonate significantly inhibited induc tion of tenascin-C. Truncated tenascin-C promoter-reporter assays using dom inant negative mutants of I kappa B alpha and I kappa B kinase beta and ele ctrophoretic mobility shift assays indicated that mechanical strain increas es tenascin-C gene transcription by activating nuclear factor-kappa B throu gh reactive oxygen species. Our findings demonstrate that mechanical strain induces tenascin-C in cardiac myocytes through a nuclear factor-kappa B de pendent and angiotensin II-independent mechanism. These data also suggest t hat reactive oxygen species may participate in mechanically induced left ve ntricular remodeling.