title: Calpains: a physiological regulator of the endothelial barrier?
abstract: The intracellular protease calpain, abundant in endothelial cells (EC), is assumed to be inactive under physiological conditions but may account for Ca2+ -linked pathophysiological events. However, nonstimulated EC contained autolyzed, activated calpain. Adding 12-48 microM calpain inhibitor I (CI) or 0.5-1 microM of the novel, membrane-permeable conjugate of calpastatin peptide-penetratin (CPP) caused rapid rounding and retraction of cultured EC (phase contrast, capacitance) and translocation of Syk, Rac, and Rho to the membrane, signifying activation upon inhibition of calpain. Isolated hearts (guinea pig) perfused with 12 microM CI or 0.5 muM CPP developed coronary leak. We conclude that calpain is constitutively active in EC and regulates vascular permeability by governing cell-cell attachment.
authors.affiliation: Department of Physiology, University of Munich, Munich, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Gonscherowski
authors.forename: Bernhard F
authors.initials: BF
authors.lastname: Becker
authors.forename: Louis
authors.initials: L
authors.lastname: Moroder
authors.forename: Elena
authors.initials: E
authors.lastname: Motrescu
authors.forename: Shirley
authors.initials: S
authors.lastname: Gil-Parrado
authors.forename: Torsten
authors.initials: T
authors.lastname: Gloe
authors.forename: Matthias
authors.initials: M
authors.lastname: Keller
authors.forename: Stefan
authors.initials: S
authors.lastname: Zahler
mesh_terms: D000818:Animals; D002154:Calpain / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000502:physiology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology*; D006168:Guinea Pigs; D006801:Humans; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D002154:Calpain