9 research outputs found
Thrombin-activated calcium signaling in the mechanism of increased endothelial permeability.
Thrombin-activated calcium signaling in the mechanism of increased endothelial permeability
The WD Motif-Containing Protein RACK-1 Functions as a Scaffold Protein Within the Type I IFN Receptor-Signaling Complex
Reversibility of increased microvessel permeability in response to VE-cadherin disassembly
Ca2+ signalling and PKCĪ± activate increased endothelial permeability by disassembly of VEācadherin junctions
The role of intracellular Ca2+ mobilization in the mechanism of increased endothelial permeability was studied. Human umbilical vein endothelial cells (HUVECs) were exposed to thapsigargin or thrombin at concentrations that resulted in similar increases in intracellular Ca2+ concentration ([Ca2+]i). The rise in [Ca2+]i in both cases was due to release of Ca2+ from intracellular stores and influx of extracellular Ca2+.Both agents decreased endothelial cell monolayer electrical resistance (a measure of endothelial cell shape change) and increased transendothelial 125I-albumin permeability. Thapsigargin induced activation of PKCĪ± and discontinuities in VE-cadherin junctions without formation of actin stress fibres. Thrombin also induced PKCĪ± activation and similar alterations in VE-cadherin junctions, but in association with actin stress fibre formation.Thapsigargin failed to promote phosphorylation of the 20 kDa myosin light chain (MLC20), whereas thrombin induced MLC20 phosphorylation consistent with formation of actin stress fibres.Calphostin C pretreatment prevented the disruption of VE-cadherin junctions and the decrease in transendothelial electrical resistance caused by both agents. Thus, the increased [Ca2+]i elicited by thapsigargin and thrombin may activate a calphostin C-sensitive PKC pathway that signals VE-cadherin junctional disassembly and increased endothelial permeability.Results suggest a critical role for Ca2+ signalling and activation of PKCĪ± in mediating the disruption of VE-cadherin junctions, and thereby in the mechanism of increased endothelial permeability