title: Induction of giant endothelial cells in culture by K-252a, a protein kinase inhibitor.
abstract: K-252a, a protein kinase inhibitor with a wide spectrum of activity, inhibited the serum-stimulated proliferation of cultured bovine carotid endothelial cells dose-dependently, and all the cells became remarkably large, with a diameter of more than 150 microns at K-252a concentrations of 0.3-1 microgram/ml. This effect of the agent was reproducible under the conditions described in this article. When the endothelial cells became abnormally large by K-252a, the surface area of the cell became wider, and the F-actin molecules increased in both number and length. Despite their abnormal size, K-252a-induced giant cells maintained at least three physiological functions characteristic to normal endothelial cells: 1) ability to take up acetylated low density lipoprotein, 2) ability to produce and secrete endothelin and 3) ability to respond via an increase of [Ca2+]i to the stimulation by bradykinin. These observations suggest that K-252a-induced giant cells are useful tools for examining the function of endothelial cells because it is very reproducible and can be produced by an easy treatment.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ohmi
authors.forename: S
authors.initials: S
authors.lastname: Yamashita
authors.forename: Y
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Nonomura
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology*; D002339:Carotid Arteries / Q000187:drug effects; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D016232:Endothelins / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D026121:Indole Alkaloids; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*
chemical_list: D000199:Actins; D002227:Carbazoles; D016232:Endothelins; D026121:Indole Alkaloids; C049985:staurosporine aglycone; D011493:Protein Kinase C; D002118:Calcium