Fluid Shear Stress Stimulates Phosphorylation of Akt in Human Endothelial Cells : Involvement in Suppression of Apoptosis

@article{citeulike:883504, abstract = {Abstract--Fluid shear stress alters the morphology and function of the endothelium by activating several kinases. Furthermore, shear stress potently inhibits apoptosis of endothelial cells. Since activation of Akt kinase has been shown to prevent cell death, we investigated the effects of shear stress on Akt phosphorylation. To test the hypothesis that shear stress interacts with the Akt kinase pathway, human umbilical venous endothelial cells were exposed to laminar shear stress (15 dyne/cm2). Western blotting with specific antibodies against the phosphorylated Akt demonstrated a time-dependent stimulation of Akt phosphorylation by shear stress with a maximal increase up to 6-fold after 1 hour of shear stress exposure. The stimulation of Akt phosphorylation by shear stress thereby seemed to be mediated by the phosphoinositide 3-OH kinase (PI3K), as evidenced by the significant inhibition of shear stress-induced Akt phosphorylation by the PI3K inhibitors wortmannin (20 nmol/L) and Ly294002 (10 {micro}mol/L). In addition, pharmacological inhibition of PI3K reduced the antiapoptotic effect of shear stress against growth factor depletion-induced apoptosis. Most important, overexpression of a dominant-negative Akt mutant significantly inhibited the apoptosis-suppressive effect of shear stress against serum depletion-induced apoptosis, thus indicating the direct involvement of shear stress-induced Akt phosphorylation for inhibition of endothelial cell apoptosis. These results define a novel shear stress-stimulated signal transduction pathway, namely, activation of the serine/threonine kinase Akt, which may contribute to the profound changes in endothelial morphology and function by shear stress.}, author = {Dimmeler, Stefanie and Assmus, Birgit and Hermann, Corinna and Haendeler, Judith and Zeiher, Andreas M. }, citeulike-article-id = {883504}, journal = {Circ Res}, keywords = {akt, apoptosis, integrin, shear}, month = {August}, number = {3}, pages = {334--341}, posted-at = {2006-10-04 08:34:15}, priority = {2}, title = {Fluid Shear Stress Stimulates Phosphorylation of Akt in Human Endothelial Cells : Involvement in Suppression of Apoptosis}, url = {http://circres.ahajournals.org/cgi/content/abstract/83/3/334}, volume = {83}, year = {1998} }

TY - JOUR ID - citeulike:883504 L3 - citeulike-article-id:883504 TI - Fluid Shear Stress Stimulates Phosphorylation of Akt in Human Endothelial Cells : Involvement in Suppression of Apoptosis JF - Circ Res VL - 83 IS - 3 SP - 334 EP - 341 N2 - Abstract--Fluid shear stress alters the morphology and function of the endothelium by activating several kinases. Furthermore, shear stress potently inhibits apoptosis of endothelial cells. Since activation of Akt kinase has been shown to prevent cell death, we investigated the effects of shear stress on Akt phosphorylation. To test the hypothesis that shear stress interacts with the Akt kinase pathway, human umbilical venous endothelial cells were exposed to laminar shear stress (15 dyne/cm2). Western blotting with specific antibodies against the phosphorylated Akt demonstrated a time-dependent stimulation of Akt phosphorylation by shear stress with a maximal increase up to 6-fold after 1 hour of shear stress exposure. The stimulation of Akt phosphorylation by shear stress thereby seemed to be mediated by the phosphoinositide 3-OH kinase (PI3K), as evidenced by the significant inhibition of shear stress-induced Akt phosphorylation by the PI3K inhibitors wortmannin (20 nmol/L) and Ly294002 (10 {micro}mol/L). In addition, pharmacological inhibition of PI3K reduced the antiapoptotic effect of shear stress against growth factor depletion-induced apoptosis. Most important, overexpression of a dominant-negative Akt mutant significantly inhibited the apoptosis-suppressive effect of shear stress against serum depletion-induced apoptosis, thus indicating the direct involvement of shear stress-induced Akt phosphorylation for inhibition of endothelial cell apoptosis. These results define a novel shear stress-stimulated signal transduction pathway, namely, activation of the serine/threonine kinase Akt, which may contribute to the profound changes in endothelial morphology and function by shear stress. KW - akt KW - apoptosis KW - integrin KW - shear AU - Dimmeler, Stefanie AU - Assmus, Birgit AU - Hermann, Corinna AU - Haendeler, Judith AU - Zeiher, Andreas PY - 1998/08/10/ UR - http://circres.ahajournals.org/cgi/content/abstract/83/3/334 ER -