Extracellular signal-regulated kinases 1 and 2 activation in endothelial cells exposed to cyclic strain

The aim of this study was to determine whether extracellular signal-regulat ed kinases 1/2 (ERK1/ERK2) are activated and might play a role in enhanced proliferation and morphological change induced by strain. Bovine aortic end othelial cells (BAEC) were subjected to an average of 6 or 10% strain at a rate of 60 cycles/min for up to 4 h. Cyclic strain caused strain- and time- dependent phosphorylation and activation of ERK1/ERK2. Peak phosphorylation and activation of ERK1/ERK2 induced by 10% strain were at 10 min. A specif ic ERK1/ERK2 kinase inhibitor, PD-98059, inhibited phosphorylation and acti vation of ERK1/ERK2 but did not inhibit the increased cell proliferation an d cell alignment induced by strain. Treatment of BAEC with 2,5-di-tert-buty l-1,4-benzohydroquinone, to deplete inositol trisphosphate-sensitive calciu m storage, and gadolinium chloride, a Ca2+ channel blocker, did not inhibit the activation of ERK1/ ERK2. Strain-induced ERK1/ERK2 activation was part ly inhibited by the protein kinase C inhibitor calphostin C and completely inhibited by the tyrosine kinase inhibitor genistein. These data suggest th at 1) ERK1/ERK2 are not critically involved in the strain-induced cell prol iferation and orientation, 2) strain-dependent activation of ERK1/ERK2 is i ndependent of intracellular and extracellular calcium mobilization, and 3) protein kinase C activation and tyrosine kinase regulate strain-induced act ivation of ERK1/ERK2.