c-Abl mediates endothelial apoptosis induced by inhibition of integrins αvβ3 and αvβ5 and by disruption of actin

摘要: Inhibition of integrins αvβ3 and αvβ5 in human brain microvascular endothelial cells (HBMECs) by the function-blocking peptide RGDfV induces loss spreading on vitronectin, cell detachment, apoptosis. We demonstrate that detachment is not required for apoptosis because plating bovine serum albumin–blocked poly-L-lysine (allows attachment, but integrin ligation spreading) also induced Latrunculin B (LatB), which inhibits F-actin polymerization, transient HBMEC their despite recovery spreading. However, LatB did cause 5 tumor lines. In HBMECs, both Y412 Y245 phosphorylation endogenous c-Abl, a nonreceptor tyrosine kinase reciprocally regulates F-actin. nuclear translocation c-Abl HBMECs. STI-571 (imatinib), targeted therapy BCR-ABL1+ leukemias inhibitor platelet-derived growth factor receptor, c-Kit, decreased LatB-induced apoptosis, its inhibition occurred 3-dimensional collagen model, supporting physiologic relevance. Last, siRNA to (but nonspecific siRNA) inhibited RGDfV- Thus, mediates αvβ3/αvβ5 or disruption