Microtubule disassembly increases endothelial cell barrier dysfunction: Role of MLC phosphorylation

Alexander Dmitriyevich Verin, Anna Birukova, Peiyi Wang, Liu Feng, Patrice Becker, Konstantin Birukov, Joe G N Garcia

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

Endothelial cell (EC) barrier regulation is critically dependent on cytoskeletal components (microfilaments and microtubules). Because several edemagenic agents induce actomyosin-driven EC contraction tightly linked to myosin light chain (MLC) phosphorylation and microfilament reorganization, we examined the role of microtubule components in bovine EC barrier regulation. Nocodazole or vinblastine, inhibitors of microtubule polymerization, significantly decreased transendothelial electrical resistance in a dose-dependent manner, whereas pretreatment with the microtubule stabilizer paclitaxel significantly attenuated this effect. Decreases in transendothelial electrical resistance induced by microtubule disruption correlated with increases in lung permeability in isolated ferret lung preparations as well as with increases in EC stress fiber content and MLC phosphorylation. The increases in MLC phosphorylation were attributed to decreases in myosin-specific phosphatase activity without significant increases in MLC kinase activity and were attenuated by paclitaxel or by several strategies (C3 exotoxin, toxin B, Rho kinase inhibition) to inhibit Rho GTPase. Together, these results suggest that microtubule disruption initiates specific signaling pathways that cross talk with microfilament networks, resulting in Rho-mediated EC contractility and barrier dysfunction.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume281
Issue number3 25-3
StatePublished - Oct 1 2001
Externally publishedYes

Fingerprint

Myosin Light Chains
Microtubules
Endothelial Cells
Phosphorylation
Actin Cytoskeleton
Paclitaxel
Electric Impedance
Myosin-Light-Chain Phosphatase
Nocodazole
Myosin-Light-Chain Kinase
Exotoxins
Actomyosin
rho-Associated Kinases
Lung
Stress Fibers
rho GTP-Binding Proteins
Ferrets
Vinblastine
Polymerization
Permeability

Keywords

  • Actin rearrangement
  • Nonmuscle contraction
  • Transendothelial electrical resistance

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Microtubule disassembly increases endothelial cell barrier dysfunction : Role of MLC phosphorylation. / Verin, Alexander Dmitriyevich; Birukova, Anna; Wang, Peiyi; Feng, Liu; Becker, Patrice; Birukov, Konstantin; Garcia, Joe G N.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 281, No. 3 25-3, 01.10.2001.

Research output: Contribution to journalArticle

Verin, Alexander Dmitriyevich ; Birukova, Anna ; Wang, Peiyi ; Feng, Liu ; Becker, Patrice ; Birukov, Konstantin ; Garcia, Joe G N. / Microtubule disassembly increases endothelial cell barrier dysfunction : Role of MLC phosphorylation. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2001 ; Vol. 281, No. 3 25-3.
@article{8de6c09663934638bd72ae4678f91f43,
title = "Microtubule disassembly increases endothelial cell barrier dysfunction: Role of MLC phosphorylation",
abstract = "Endothelial cell (EC) barrier regulation is critically dependent on cytoskeletal components (microfilaments and microtubules). Because several edemagenic agents induce actomyosin-driven EC contraction tightly linked to myosin light chain (MLC) phosphorylation and microfilament reorganization, we examined the role of microtubule components in bovine EC barrier regulation. Nocodazole or vinblastine, inhibitors of microtubule polymerization, significantly decreased transendothelial electrical resistance in a dose-dependent manner, whereas pretreatment with the microtubule stabilizer paclitaxel significantly attenuated this effect. Decreases in transendothelial electrical resistance induced by microtubule disruption correlated with increases in lung permeability in isolated ferret lung preparations as well as with increases in EC stress fiber content and MLC phosphorylation. The increases in MLC phosphorylation were attributed to decreases in myosin-specific phosphatase activity without significant increases in MLC kinase activity and were attenuated by paclitaxel or by several strategies (C3 exotoxin, toxin B, Rho kinase inhibition) to inhibit Rho GTPase. Together, these results suggest that microtubule disruption initiates specific signaling pathways that cross talk with microfilament networks, resulting in Rho-mediated EC contractility and barrier dysfunction.",
keywords = "Actin rearrangement, Nonmuscle contraction, Transendothelial electrical resistance",
author = "Verin, {Alexander Dmitriyevich} and Anna Birukova and Peiyi Wang and Liu Feng and Patrice Becker and Konstantin Birukov and Garcia, {Joe G N}",
year = "2001",
month = "10",
day = "1",
language = "English (US)",
volume = "281",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "3 25-3",

}

TY - JOUR

T1 - Microtubule disassembly increases endothelial cell barrier dysfunction

T2 - Role of MLC phosphorylation

AU - Verin, Alexander Dmitriyevich

AU - Birukova, Anna

AU - Wang, Peiyi

AU - Feng, Liu

AU - Becker, Patrice

AU - Birukov, Konstantin

AU - Garcia, Joe G N

PY - 2001/10/1

Y1 - 2001/10/1

N2 - Endothelial cell (EC) barrier regulation is critically dependent on cytoskeletal components (microfilaments and microtubules). Because several edemagenic agents induce actomyosin-driven EC contraction tightly linked to myosin light chain (MLC) phosphorylation and microfilament reorganization, we examined the role of microtubule components in bovine EC barrier regulation. Nocodazole or vinblastine, inhibitors of microtubule polymerization, significantly decreased transendothelial electrical resistance in a dose-dependent manner, whereas pretreatment with the microtubule stabilizer paclitaxel significantly attenuated this effect. Decreases in transendothelial electrical resistance induced by microtubule disruption correlated with increases in lung permeability in isolated ferret lung preparations as well as with increases in EC stress fiber content and MLC phosphorylation. The increases in MLC phosphorylation were attributed to decreases in myosin-specific phosphatase activity without significant increases in MLC kinase activity and were attenuated by paclitaxel or by several strategies (C3 exotoxin, toxin B, Rho kinase inhibition) to inhibit Rho GTPase. Together, these results suggest that microtubule disruption initiates specific signaling pathways that cross talk with microfilament networks, resulting in Rho-mediated EC contractility and barrier dysfunction.

AB - Endothelial cell (EC) barrier regulation is critically dependent on cytoskeletal components (microfilaments and microtubules). Because several edemagenic agents induce actomyosin-driven EC contraction tightly linked to myosin light chain (MLC) phosphorylation and microfilament reorganization, we examined the role of microtubule components in bovine EC barrier regulation. Nocodazole or vinblastine, inhibitors of microtubule polymerization, significantly decreased transendothelial electrical resistance in a dose-dependent manner, whereas pretreatment with the microtubule stabilizer paclitaxel significantly attenuated this effect. Decreases in transendothelial electrical resistance induced by microtubule disruption correlated with increases in lung permeability in isolated ferret lung preparations as well as with increases in EC stress fiber content and MLC phosphorylation. The increases in MLC phosphorylation were attributed to decreases in myosin-specific phosphatase activity without significant increases in MLC kinase activity and were attenuated by paclitaxel or by several strategies (C3 exotoxin, toxin B, Rho kinase inhibition) to inhibit Rho GTPase. Together, these results suggest that microtubule disruption initiates specific signaling pathways that cross talk with microfilament networks, resulting in Rho-mediated EC contractility and barrier dysfunction.

KW - Actin rearrangement

KW - Nonmuscle contraction

KW - Transendothelial electrical resistance

UR - http://www.scopus.com/inward/record.url?scp=0034828134&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034828134&partnerID=8YFLogxK

M3 - Article

C2 - 11504682

AN - SCOPUS:0034828134

VL - 281

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 3 25-3

ER -