Review

Molecular mechanisms of thrombin-induced endothelial cell permeability

N. V. Bogacheva, Joe GN Garcia, A. D. Verin

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Confluent endothelium serves as a selective barrier between the vascular space of blood vessels and underlying tissues. Compromised barrier function of the endothelium in response to inflammation mediators, such as thrombin, is accompanied by reversible cell rounding and interendothelial gap formation. Endothelial barrier integrity substantially depends on the cytoskeleton, which ensures actin stress fiber formation and via actomyosin-driven contraction regulates cell shape and adhesion. Recent studies have shown the sequence of events that mediate signal transduction in endothelial cells. Binding of thrombin with its receptor initiates activation of heterotrimeric G-proteins, which, in turn, entails a decrease in cAMP level in the cell, increase in intracellular Ca2+ and diacylglycerol concentration, and activation of the small G-protein Rho. Phosphorylation of myosin light chains as a result of activation of myosin light chain kinase and inactivation of myosin phosphatases stimulates stress fiber formation and triggers actomyosin contraction. In addition, thrombin-induced rearrangement in the endothelial cytoskeleton is regulated by Ca2+/calmodulin-dependent protein kinase, protein kinase C, and tyrosine protein kinases. This review focuses on presently known biochemical mechanisms of cell response to thrombin and their role in endothelial barrier dysfunction.

Original languageEnglish (US)
Pages (from-to)88-98
Number of pages11
JournalBiokhimiya
Volume67
Issue number1
StatePublished - 2002
Externally publishedYes

Fingerprint

Endothelial cells
Thrombin
Actomyosin
Chemical activation
Myosin-Light-Chain Phosphatase
Myosin-Light-Chain Kinase
Heterotrimeric GTP-Binding Proteins
Inflammation Mediators
Signal transduction
Calcium-Calmodulin-Dependent Protein Kinases
Myosin Light Chains
Phosphorylation
Monomeric GTP-Binding Proteins
Fibers
Diglycerides
Blood vessels
Protein-Tyrosine Kinases
Protein Kinase C
Actins
Adhesion

Keywords

  • Barrier function
  • Endothelium
  • Thrombin

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Review : Molecular mechanisms of thrombin-induced endothelial cell permeability. / Bogacheva, N. V.; Garcia, Joe GN; Verin, A. D.

In: Biokhimiya, Vol. 67, No. 1, 2002, p. 88-98.

Research output: Contribution to journalArticle

Bogacheva, N. V. ; Garcia, Joe GN ; Verin, A. D. / Review : Molecular mechanisms of thrombin-induced endothelial cell permeability. In: Biokhimiya. 2002 ; Vol. 67, No. 1. pp. 88-98.
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