Molecular mechanisms of thrombin-induced endothelial cell permeability.

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

Research output: Contribution to journalArticle

141 Citations (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)75-84
Number of pages10
JournalBiochemistry (Moscow)
Volume67
Issue number1
StatePublished - Jan 2002
Externally publishedYes

Fingerprint

Endothelial cells
Thrombin
Permeability
Endothelial Cells
Actomyosin
Stress Fibers
Chemical activation
Cytoskeleton
Endothelium
Blood Vessels
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
Cell Shape

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

Cite this

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

In: Biochemistry (Moscow), Vol. 67, No. 1, 01.2002, p. 75-84.

Research output: Contribution to journalArticle

Bogatcheva, N. V. ; Garcia, Joe GN ; Verin, A. D. / Molecular mechanisms of thrombin-induced endothelial cell permeability. In: Biochemistry (Moscow). 2002 ; Vol. 67, No. 1. pp. 75-84.
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