Disruption of the actin cytoskeleton elicits profound changes in cell survival 
and function. The actin cytoskeleton is regulated in a hierarchical manner by 
Rho GTPases. Rho kinase, a downstream effector of RhoA, regulates the formation 
of stress fibers and focal adhesions. Disruption of the actin cytoskeleton 
causes apoptosis in airway epithelial cells. To examine further the relation of 
cytoskeletal integrity and apoptosis, we tested whether inhibition of Rho kinase 
would elicit apoptosis in airway epithelial cells. Inhibition with either 
Y-27632 or HA1077 induced membrane ruffling and loss of actin stress fibers, and 
apoptosis in airway epithelial cells that was blocked by inhibiting caspase 
function or by inhibiting protein synthesis. Cells overexpressing constitutively 
active Rho kinase, but not native Rho kinase, were resistant to Rho kinase 
inhibitor-induced stress fiber disruption and apoptosis. Inhibition of Rho 
kinase disrupted actin stress fibers but did not induce apoptosis in 3T3 cells. 
We demonstrate that Rho kinase inhibition induces airway epithelial cell 
apoptosis associated with changes in actin filament integrity. Our data suggest 
that Rho kinase may be a regulator of early initiation of apoptosis.