The applicant proposes to test the hypothesis that a cardiac myocyte is sensitive to the direction, or spatial context, when an episode of stretch is applied across the cell. The aligned myocyte cell system will be used to measure how different degrees and directions of stretch regulate the expression and metabolism of alpha and beta myosin heavy chain (aMHC & bMHC), a1 and b1 integrin and b-tubulin.
The specific aims are: 1) to determine the effects of different vectors of stretch on the metabolism of selected cardiac proteins; 2) to determine how selective changes in cardiac metabolism and cytoskeletal organization alter the concentration of specific cardiac proteins; and 3) to experimentally manipulate the profile of integrins present on the surface of cultured myocytes.
Dobson, Allison W; Grishko, Valentina; LeDoux, Susan P et al. (2002) Enhanced mtDNA repair capacity protects pulmonary artery endothelial cells from oxidant-mediated death. Am J Physiol Lung Cell Mol Physiol 283:L205-10 |
Grishko, V; Solomon, M; Wilson, G L et al. (2001) Oxygen radical-induced mitochondrial DNA damage and repair in pulmonary vascular endothelial cell phenotypes. Am J Physiol Lung Cell Mol Physiol 280:L1300-8 |
Killilea, D W; Hester, R; Balczon, R et al. (2000) Free radical production in hypoxic pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 279:L408-12 |
Simpson, D G; Majeski, M; Borg, T K et al. (1999) Regulation of cardiac myocyte protein turnover and myofibrillar structure in vitro by specific directions of stretch. Circ Res 85:e59-69 |