Hypoxia-induced Alterations in Cytoskeleton Coincide with Collagenase Expression in Cultured Neonatal Rat Cardiomyocytes,

Incubation of cultured neonatal rat cardiomyocytes in hypoxic conditions, mimicking the deprivation of O2which occurs duringin situmyocardial ischemia, leads to a progressive change in cardiomyocytes cytoskeletal components. Confocal scanning laser immunofluorescence microscopy (CSLIM) reveals that the typical striated costameric distribution of vinculin gradually disappears to be replaced by circular, vinculin-containing sarcolemmal rosettes. There is little change in distribution of vinculin in the focal adhesions or in the intercalated disks. This cytoskeletal alteration, like that observed in virally transformed fibroblasts and phorbol ester-treated skeletal myoblasts, is inhibited by genistein, a tyrosine kinase inhibitor. Increased exposure to hypoxic conditions also produces an increase in a 92-kDa collagenase which is immunolocalized only to cardiomyocytes. As with the rosette formation, genistein also inhibits the increased expression of the 92-kDa collagenase. We suggest that this cytoskeletal change with attendant release of 92 kDa collagenase may represent a defensive mechanism on the part of the cardiomyocyte to reduce damage by reducing the cellular coupling to the extracellular collagenous matrix, thereby lessening the stresses imposed by contractile forces.