The cysteine protease inhibitor, E-64, stimulates the polarization and locomotor responses of endothelial cells to wounding.
To clarify the role of proteases and protease inhibitors in the initiation and execution of endothelial cell movement, we observed the effect of several protease inhibitors on the polarization and locomotor responses of an endothelial cell monolayer subjected to experimental wounding. We found that the thiol protease inhibitor, E-64 (L-transepoxysuccinyl-leucylamido-[4-guanidino]butane) stimulated both cellular processes. The stimulatory effect of E-64 on the polarization response of cells to wounding required a preincubation period of at least 1 hr, calcium-calmodulin interaction, protein kinase C activation, and was blocked by cyclic AMP analogs. The chemokinetic action of E-64 appears to be unique among the protease inhibitors tested and may represent a novel role for this cysteine protease inhibitor or its endogenous counterpart in the modulation of cell locomotion.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000494:pharmacology; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors; D004730:Endothelium, Vascular / Q000187:drug effects*; D004789:Enzyme Activation; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D008858:Microscopy, Phase-Contrast; D011493:Protein Kinase C / Q000378:metabolism
D002147:Calmodulin; D015853:Cysteine Proteinase Inhibitors; D000001:Calcimycin; D011493:Protein Kinase C; D007930:Leucine; C024974:E 64; D002118:Calcium