Calpains: a physiological regulator of the endothelial barrier?
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.
Gonscherowski
Vera
V
Department of Physiology, University of Munich, Munich, Germany.
Becker
Bernhard F
BF
Moroder
Louis
L
Motrescu
Elena
E
Gil-Parrado
Shirley
S
Gloe
Torsten
T
Keller
Matthias
M
Zahler
Stefan
S
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
D002154:Calpain