TIMAP protects endothelial barrier from LPS-induced vascular leakage and is down-regulated by LPS

Christophe Poirier, Boris A. Gorshkov, Marina A. Zemskova, Natalia V. Bogatcheva, Alexander D. Verin

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

TIMAP is a regulatory subunit of protein phosphatase 1, whose role remains largely unknown. Our recent data suggested that TIMAP is involved in the regulation of barrier function in cultured pulmonary endothelial monolayers [Csortos et al., 2008. Am. J. Physiol. Lung Cell. Mol. Physiol. 295, L440-L450]. Here we showed that TIMAP depletion exacerbates lipopolysaccharide (LPS)-induced vascular leakage in murine lung, suggesting that TIMAP has a barrier-protective role in vivo. Real-Time RT PCR analysis revealed that treatment with LPS significantly suppressed Timap mRNA level. This suppression was not achieved via the down-regulation of Timap promoter activity, suggesting that LPS decreased Timap mRNA stability. Pretreatment with protein kinase A (PKA) inhibitor H-89 reduced TIMAP mRNA level, whereas pretreatment with PKA activator, bnz-cAMP, increased this level and attenuated LPS-induced decrease in TIMAP mRNA. Altogether, these data confirmed the barrier-protective role of TIMAP and suggested that barrier-disruptive and barrier-protective agents may employ modulation of TIMAP expression as a mechanism affecting barrier permeability.

Original languageEnglish (US)
Pages (from-to)334-337
Number of pages4
JournalRespiratory Physiology and Neurobiology
Volume179
Issue number2-3
DOIs
StatePublished - Dec 15 2011

Fingerprint

Blood Vessels
Lipopolysaccharides
Cyclic AMP-Dependent Protein Kinases
Lung
Messenger RNA
Protein Phosphatase 1
Protective Agents
RNA Stability
Protein Kinase Inhibitors
Real-Time Polymerase Chain Reaction
Permeability
Down-Regulation

Keywords

  • Barrier dysfunction
  • LPS
  • PKA
  • PPP1R16B
  • TIMAP

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pulmonary and Respiratory Medicine

Cite this

TIMAP protects endothelial barrier from LPS-induced vascular leakage and is down-regulated by LPS. / Poirier, Christophe; Gorshkov, Boris A.; Zemskova, Marina A.; Bogatcheva, Natalia V.; Verin, Alexander D.

In: Respiratory Physiology and Neurobiology, Vol. 179, No. 2-3, 15.12.2011, p. 334-337.

Research output: Contribution to journalArticle

Poirier, Christophe ; Gorshkov, Boris A. ; Zemskova, Marina A. ; Bogatcheva, Natalia V. ; Verin, Alexander D. / TIMAP protects endothelial barrier from LPS-induced vascular leakage and is down-regulated by LPS. In: Respiratory Physiology and Neurobiology. 2011 ; Vol. 179, No. 2-3. pp. 334-337.
@article{2c6773ffae0a4cd795141ab0ea66cfd8,
title = "TIMAP protects endothelial barrier from LPS-induced vascular leakage and is down-regulated by LPS",
abstract = "TIMAP is a regulatory subunit of protein phosphatase 1, whose role remains largely unknown. Our recent data suggested that TIMAP is involved in the regulation of barrier function in cultured pulmonary endothelial monolayers [Csortos et al., 2008. Am. J. Physiol. Lung Cell. Mol. Physiol. 295, L440-L450]. Here we showed that TIMAP depletion exacerbates lipopolysaccharide (LPS)-induced vascular leakage in murine lung, suggesting that TIMAP has a barrier-protective role in vivo. Real-Time RT PCR analysis revealed that treatment with LPS significantly suppressed Timap mRNA level. This suppression was not achieved via the down-regulation of Timap promoter activity, suggesting that LPS decreased Timap mRNA stability. Pretreatment with protein kinase A (PKA) inhibitor H-89 reduced TIMAP mRNA level, whereas pretreatment with PKA activator, bnz-cAMP, increased this level and attenuated LPS-induced decrease in TIMAP mRNA. Altogether, these data confirmed the barrier-protective role of TIMAP and suggested that barrier-disruptive and barrier-protective agents may employ modulation of TIMAP expression as a mechanism affecting barrier permeability.",
keywords = "Barrier dysfunction, LPS, PKA, PPP1R16B, TIMAP",
author = "Christophe Poirier and Gorshkov, {Boris A.} and Zemskova, {Marina A.} and Bogatcheva, {Natalia V.} and Verin, {Alexander D.}",
year = "2011",
month = "12",
day = "15",
doi = "10.1016/j.resp.2011.08.012",
language = "English (US)",
volume = "179",
pages = "334--337",
journal = "Respiratory Physiology and Neurobiology",
issn = "1569-9048",
publisher = "Elsevier",
number = "2-3",

}

TY - JOUR

T1 - TIMAP protects endothelial barrier from LPS-induced vascular leakage and is down-regulated by LPS

AU - Poirier, Christophe

AU - Gorshkov, Boris A.

AU - Zemskova, Marina A.

AU - Bogatcheva, Natalia V.

AU - Verin, Alexander D.

PY - 2011/12/15

Y1 - 2011/12/15

N2 - TIMAP is a regulatory subunit of protein phosphatase 1, whose role remains largely unknown. Our recent data suggested that TIMAP is involved in the regulation of barrier function in cultured pulmonary endothelial monolayers [Csortos et al., 2008. Am. J. Physiol. Lung Cell. Mol. Physiol. 295, L440-L450]. Here we showed that TIMAP depletion exacerbates lipopolysaccharide (LPS)-induced vascular leakage in murine lung, suggesting that TIMAP has a barrier-protective role in vivo. Real-Time RT PCR analysis revealed that treatment with LPS significantly suppressed Timap mRNA level. This suppression was not achieved via the down-regulation of Timap promoter activity, suggesting that LPS decreased Timap mRNA stability. Pretreatment with protein kinase A (PKA) inhibitor H-89 reduced TIMAP mRNA level, whereas pretreatment with PKA activator, bnz-cAMP, increased this level and attenuated LPS-induced decrease in TIMAP mRNA. Altogether, these data confirmed the barrier-protective role of TIMAP and suggested that barrier-disruptive and barrier-protective agents may employ modulation of TIMAP expression as a mechanism affecting barrier permeability.

AB - TIMAP is a regulatory subunit of protein phosphatase 1, whose role remains largely unknown. Our recent data suggested that TIMAP is involved in the regulation of barrier function in cultured pulmonary endothelial monolayers [Csortos et al., 2008. Am. J. Physiol. Lung Cell. Mol. Physiol. 295, L440-L450]. Here we showed that TIMAP depletion exacerbates lipopolysaccharide (LPS)-induced vascular leakage in murine lung, suggesting that TIMAP has a barrier-protective role in vivo. Real-Time RT PCR analysis revealed that treatment with LPS significantly suppressed Timap mRNA level. This suppression was not achieved via the down-regulation of Timap promoter activity, suggesting that LPS decreased Timap mRNA stability. Pretreatment with protein kinase A (PKA) inhibitor H-89 reduced TIMAP mRNA level, whereas pretreatment with PKA activator, bnz-cAMP, increased this level and attenuated LPS-induced decrease in TIMAP mRNA. Altogether, these data confirmed the barrier-protective role of TIMAP and suggested that barrier-disruptive and barrier-protective agents may employ modulation of TIMAP expression as a mechanism affecting barrier permeability.

KW - Barrier dysfunction

KW - LPS

KW - PKA

KW - PPP1R16B

KW - TIMAP

UR - http://www.scopus.com/inward/record.url?scp=81155123118&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=81155123118&partnerID=8YFLogxK

U2 - 10.1016/j.resp.2011.08.012

DO - 10.1016/j.resp.2011.08.012

M3 - Article

C2 - 21907835

AN - SCOPUS:81155123118

VL - 179

SP - 334

EP - 337

JO - Respiratory Physiology and Neurobiology

JF - Respiratory Physiology and Neurobiology

SN - 1569-9048

IS - 2-3

ER -