The leading role of microtubules in endothelial barrier dysfunction: Disassembly of peripheral microtubules leaves behind the cytoskeletal reorganization

Irina B. Alieva, Evgeny Alexandrovich Zemskov, Ksenija M. Smurova, Irina N. Kaverina, Alexander Dmitriyevich Verin

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Disturbance of the endothelial barrier is characterized by dramatic cytoskeleton reorganization, activation of actomyosin contraction and, finally, leads to intercellular gap formation. Here we demonstrate that the edemagenic agent, thrombin, causes a rapid increase in the human pulmonary artery endothelial cell (EC) barrier permeability accompanied by fast decreasing in the peripheral microtubules quantity and reorganization of the microtubule system in the internal cytoplasm of the EC within 5 min of the treatment. The actin stress-fibers formation occurs gradually and the maximal effect is observed relatively later, 30 min of the thrombin treatment. Thus, microtubules reaction develops faster than the reorganization of the actin filaments system responsible for the subsequent changes of the cell shape during barrier dysfunction development. Direct microtubules depolymerization by nocodazole initiates the cascade of barrier dysfunction reactions. Nocodazole-induced barrier disruption is connected directly with the degree of peripheral microtubules depolymerization. Short-term loss of endothelial barrier function occurs at the minimal destruction of peripheral microtubules, when actin filament system is still intact. Specifically, we demonstrate that the EC microtubule dynamics examined by time-lapse imaging of EB3-GFP comets movement has changed under these conditions: microtubule plus ends growth rate significantly decreased near the cell periphery. The microtubules, apparently, are the first target in the circuit of reactions leading to the pulmonary EC barrier compromise. Our results show that dynamic microtubules play an essential role in the barrier function in vitro; peripheral microtubules depolymerization is necessary and sufficient condition for initiation of endothelial barrier dysfunction. J. Cell. Biochem. 114: 2258-2272, 2013. © 2013 Wiley Periodicals, Inc.

Original languageEnglish (US)
Pages (from-to)2258-2272
Number of pages15
JournalJournal of Cellular Biochemistry
Volume114
Issue number10
DOIs
StatePublished - Oct 1 2013

Fingerprint

Endothelial cells
Microtubules
Depolymerization
Nocodazole
Actins
Thrombin
Actomyosin
Endothelial Cells
Chemical activation
Actin Cytoskeleton
Imaging techniques
Networks (circuits)
Fibers
Time-Lapse Imaging
Stress Fibers
Cell Shape
Cytoskeleton
Pulmonary Artery
Permeability
Cytoplasm

Keywords

  • ENDOTHELIAL BARRIER DYSFUNCTION
  • ENDOTHELIAL BARRIER FUNCTION
  • HUMAN PULMONARY ENDOTHELIUM
  • MICROTUBULE DYNAMICS
  • MICROTUBULES

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

The leading role of microtubules in endothelial barrier dysfunction : Disassembly of peripheral microtubules leaves behind the cytoskeletal reorganization. / Alieva, Irina B.; Zemskov, Evgeny Alexandrovich; Smurova, Ksenija M.; Kaverina, Irina N.; Verin, Alexander Dmitriyevich.

In: Journal of Cellular Biochemistry, Vol. 114, No. 10, 01.10.2013, p. 2258-2272.

Research output: Contribution to journalArticle

@article{96fd7458c45d4425a33a4fda68a0ce0c,
title = "The leading role of microtubules in endothelial barrier dysfunction: Disassembly of peripheral microtubules leaves behind the cytoskeletal reorganization",
abstract = "Disturbance of the endothelial barrier is characterized by dramatic cytoskeleton reorganization, activation of actomyosin contraction and, finally, leads to intercellular gap formation. Here we demonstrate that the edemagenic agent, thrombin, causes a rapid increase in the human pulmonary artery endothelial cell (EC) barrier permeability accompanied by fast decreasing in the peripheral microtubules quantity and reorganization of the microtubule system in the internal cytoplasm of the EC within 5 min of the treatment. The actin stress-fibers formation occurs gradually and the maximal effect is observed relatively later, 30 min of the thrombin treatment. Thus, microtubules reaction develops faster than the reorganization of the actin filaments system responsible for the subsequent changes of the cell shape during barrier dysfunction development. Direct microtubules depolymerization by nocodazole initiates the cascade of barrier dysfunction reactions. Nocodazole-induced barrier disruption is connected directly with the degree of peripheral microtubules depolymerization. Short-term loss of endothelial barrier function occurs at the minimal destruction of peripheral microtubules, when actin filament system is still intact. Specifically, we demonstrate that the EC microtubule dynamics examined by time-lapse imaging of EB3-GFP comets movement has changed under these conditions: microtubule plus ends growth rate significantly decreased near the cell periphery. The microtubules, apparently, are the first target in the circuit of reactions leading to the pulmonary EC barrier compromise. Our results show that dynamic microtubules play an essential role in the barrier function in vitro; peripheral microtubules depolymerization is necessary and sufficient condition for initiation of endothelial barrier dysfunction. J. Cell. Biochem. 114: 2258-2272, 2013. {\circledC} 2013 Wiley Periodicals, Inc.",
keywords = "ENDOTHELIAL BARRIER DYSFUNCTION, ENDOTHELIAL BARRIER FUNCTION, HUMAN PULMONARY ENDOTHELIUM, MICROTUBULE DYNAMICS, MICROTUBULES",
author = "Alieva, {Irina B.} and Zemskov, {Evgeny Alexandrovich} and Smurova, {Ksenija M.} and Kaverina, {Irina N.} and Verin, {Alexander Dmitriyevich}",
year = "2013",
month = "10",
day = "1",
doi = "10.1002/jcb.24575",
language = "English (US)",
volume = "114",
pages = "2258--2272",
journal = "Journal of Cellular Biochemistry",
issn = "0730-2312",
publisher = "Wiley-Liss Inc.",
number = "10",

}

TY - JOUR

T1 - The leading role of microtubules in endothelial barrier dysfunction

T2 - Disassembly of peripheral microtubules leaves behind the cytoskeletal reorganization

AU - Alieva, Irina B.

AU - Zemskov, Evgeny Alexandrovich

AU - Smurova, Ksenija M.

AU - Kaverina, Irina N.

AU - Verin, Alexander Dmitriyevich

PY - 2013/10/1

Y1 - 2013/10/1

N2 - Disturbance of the endothelial barrier is characterized by dramatic cytoskeleton reorganization, activation of actomyosin contraction and, finally, leads to intercellular gap formation. Here we demonstrate that the edemagenic agent, thrombin, causes a rapid increase in the human pulmonary artery endothelial cell (EC) barrier permeability accompanied by fast decreasing in the peripheral microtubules quantity and reorganization of the microtubule system in the internal cytoplasm of the EC within 5 min of the treatment. The actin stress-fibers formation occurs gradually and the maximal effect is observed relatively later, 30 min of the thrombin treatment. Thus, microtubules reaction develops faster than the reorganization of the actin filaments system responsible for the subsequent changes of the cell shape during barrier dysfunction development. Direct microtubules depolymerization by nocodazole initiates the cascade of barrier dysfunction reactions. Nocodazole-induced barrier disruption is connected directly with the degree of peripheral microtubules depolymerization. Short-term loss of endothelial barrier function occurs at the minimal destruction of peripheral microtubules, when actin filament system is still intact. Specifically, we demonstrate that the EC microtubule dynamics examined by time-lapse imaging of EB3-GFP comets movement has changed under these conditions: microtubule plus ends growth rate significantly decreased near the cell periphery. The microtubules, apparently, are the first target in the circuit of reactions leading to the pulmonary EC barrier compromise. Our results show that dynamic microtubules play an essential role in the barrier function in vitro; peripheral microtubules depolymerization is necessary and sufficient condition for initiation of endothelial barrier dysfunction. J. Cell. Biochem. 114: 2258-2272, 2013. © 2013 Wiley Periodicals, Inc.

AB - Disturbance of the endothelial barrier is characterized by dramatic cytoskeleton reorganization, activation of actomyosin contraction and, finally, leads to intercellular gap formation. Here we demonstrate that the edemagenic agent, thrombin, causes a rapid increase in the human pulmonary artery endothelial cell (EC) barrier permeability accompanied by fast decreasing in the peripheral microtubules quantity and reorganization of the microtubule system in the internal cytoplasm of the EC within 5 min of the treatment. The actin stress-fibers formation occurs gradually and the maximal effect is observed relatively later, 30 min of the thrombin treatment. Thus, microtubules reaction develops faster than the reorganization of the actin filaments system responsible for the subsequent changes of the cell shape during barrier dysfunction development. Direct microtubules depolymerization by nocodazole initiates the cascade of barrier dysfunction reactions. Nocodazole-induced barrier disruption is connected directly with the degree of peripheral microtubules depolymerization. Short-term loss of endothelial barrier function occurs at the minimal destruction of peripheral microtubules, when actin filament system is still intact. Specifically, we demonstrate that the EC microtubule dynamics examined by time-lapse imaging of EB3-GFP comets movement has changed under these conditions: microtubule plus ends growth rate significantly decreased near the cell periphery. The microtubules, apparently, are the first target in the circuit of reactions leading to the pulmonary EC barrier compromise. Our results show that dynamic microtubules play an essential role in the barrier function in vitro; peripheral microtubules depolymerization is necessary and sufficient condition for initiation of endothelial barrier dysfunction. J. Cell. Biochem. 114: 2258-2272, 2013. © 2013 Wiley Periodicals, Inc.

KW - ENDOTHELIAL BARRIER DYSFUNCTION

KW - ENDOTHELIAL BARRIER FUNCTION

KW - HUMAN PULMONARY ENDOTHELIUM

KW - MICROTUBULE DYNAMICS

KW - MICROTUBULES

UR - http://www.scopus.com/inward/record.url?scp=84882378094&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84882378094&partnerID=8YFLogxK

U2 - 10.1002/jcb.24575

DO - 10.1002/jcb.24575

M3 - Article

C2 - 23606375

AN - SCOPUS:84882378094

VL - 114

SP - 2258

EP - 2272

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

IS - 10

ER -