Ca2+ signalling and PKCα activate increased endothelial permeability by disassembly of VE—cadherin junctions

• DOI: 10.1111/j.1469-7793.2001.0433a.x
• Publication Date: 2004-08-05T10:08:46Z
• Authors: Raudel Sandoval; Asrar B. Malik; Richard D. Minshall; Panos Kouklis; Chad A. Ellis; Chinnaswamy Tirup...
• Keywords: Thapsigargin; Calphostin C; VE-cadherin; Adherens junction

The role of intracellular Ca 2+ mobilization in the mechanism increased endothelial permeability was studied. Human umbilical vein cells (HUVECs) were exposed to thapsigargin or thrombin at concentrations that resulted similar increases concentration ([Ca ] i ) . rise [Ca both cases due release from stores and influx extracellular Both agents decreased cell monolayer electrical resistance (a measure shape change) transendothelial 125 I‐albumin permeability. Thapsigargin induced activation PKCα discontinuities VE‐cadherin junctions without formation actin stress fibres. Thrombin also alterations junctions, but association with fibre formation. failed promote phosphorylation 20 kDa myosin light chain (MLC ), whereas MLC consistent Calphostin C pretreatment prevented disruption decrease caused by agents. Thus, elicited may activate a calphostin C‐sensitive PKC pathway signals junctional disassembly Results suggest critical for signalling mediating thereby