HYPOXIA-INDUCED ALTERATIONS IN CYTOSKELETON COINCIDE WITH COLLAGENASEEXPRESSION IN CULTURED NEONATAL RAT CARDIOMYOCYTES

Incubation of cultured neonatal rat cardiomyocytes in hypoxic conditio ns, mimicking the deprivation of O-2 which occurs during in situ myoca rdial ischemia, leads to a progressive change in cardiomyocytes cytosk eletal components. Confocal scanning laser immunofluorescence microsco py (CSLIM) reveals that the typical striated costameric distribution o f vinculin gradually disappears to be replaced by circular, vinculin-c ontaining 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 fi broblasts and phorbol ester-treated skeletal myoblasts, is inhibited b y genistein, a tyrosine kinase inhibitor. Increased exposure to hypoxi c conditions also produces an increase in a 92-kDa collagenase which i s immunolocalized only to cardiomyocytes. As with the rosette formatio n, genistein also inhibits the increased expression of the 92-kDa coll agenase. We suggest that this cytoskeletal change with attendant relea se of 92 kDa collagenase may represent a defensive mechanism on the pa rt of the cardiomyocyte to reduce damage by reducing the cellular coup ling to the extracellular collagenous matrix, thereby lessening the st resses imposed by contractile forces.