MODULATION OF GAP-JUNCTIONS IN SENESCENT ENDOTHELIAL-CELLS

Gap junction-mediated intercellular communication (GJIC) was decreased in senescent human umbilical vein endothelial cells (HUVEC), as detec ted by Gap-Frap studies. The molecular basis of this reduction and the effects of the calcium ionophore A23187 and epidermal growth factor ( EGF) on young and old HUVEC have been investigated. Northern and Weste rn analyses reveal that the levels of both cx43 (connexin 43) messenge r RNA and protein decline as HUVEC age in vitro. While both young and senescent cells responded immediately to increases in intracellular ca lcium concentrations, only young cells produced a dose-dependent decre ase in cell coupling in response to the addition of exogenous EGF. The down-regulation of cx43 mRNA and protein levels in senescent endothel ial cells suggests that GJIC might play a role in the aging process. T he inability of senescent cells to down-regulate gap junctions in resp onse to EGF reflects a defect in the regulatory mechanism of gap junct ion activity in senescent cells. (C) Academic Press, Inc.