Taxol alleviates 2-methoxyestradiol-induced endothelial permeability

Boris A Gorshkov, Alexander Dmitriyevich Verin, Marina A. Zemskova, Natalia V. Bogatcheva

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

We have previously shown that the anti-cancer agent 2-methoxyestradiol (2ME) induces hyperpermeability across endothelial monolayers. Here, we show that both microtubule disruptor, 2ME, and microtubule stabilizer, paclitaxel (taxol), increase vascular lung permeability in vitro and in vivo. Simultaneous application of 2ME and taxol alleviates 2ME-induced endothelial barrier dysfunction, which is evident by the decreased Evans Blue Dye accumulation in lung tissue and increased transendothelial resistance across monolayers. 2ME significantly increases the level of p38 and MLC phosphorylation in both endothelial monolayers and murine lungs; this increase is suppressed in the presence of taxol. Taxol treatment leads to an immediate and sustained increase in tubulin acetylation in human pulmonary artery endothelial cells (HPAEC). Surprisingly, 2ME treatment also increases tubulin acetylation; however, the onset of this process is delayed and coincides with the stage of a partial barrier restoration in HPAEC monolayer. Inhibition of histone deacetylase 6 (HDAC6) with tubacin increases tubulin acetylation level, suppresses 2ME-induced HSP27 and MLC phosphorylation, and decreases 2ME-induced barrier dysfunction, suggesting barrier-protective and/or barrier-restorative role for tubulin acetylation in vascular endothelium.

Original languageEnglish (US)
Pages (from-to)56-63
Number of pages8
JournalVascular Pharmacology
Volume56
Issue number1-2
DOIs
StatePublished - Jan 1 2012

Fingerprint

Paclitaxel
Permeability
Tubulin
Acetylation
Microtubules
Lung
Pulmonary Artery
Endothelial Cells
Phosphorylation
Evans Blue
Histone Deacetylases
2-methoxyestradiol
Vascular Endothelium
Capillary Permeability
Coloring Agents
Neoplasms

Keywords

  • 2-methoxyestradiol
  • Barrier dysfunction
  • Taxol
  • Tubulin acetylation

ASJC Scopus subject areas

  • Physiology
  • Molecular Medicine
  • Pharmacology

Cite this

Taxol alleviates 2-methoxyestradiol-induced endothelial permeability. / Gorshkov, Boris A; Verin, Alexander Dmitriyevich; Zemskova, Marina A.; Bogatcheva, Natalia V.

In: Vascular Pharmacology, Vol. 56, No. 1-2, 01.01.2012, p. 56-63.

Research output: Contribution to journalArticle

Gorshkov, Boris A ; Verin, Alexander Dmitriyevich ; Zemskova, Marina A. ; Bogatcheva, Natalia V. / Taxol alleviates 2-methoxyestradiol-induced endothelial permeability. In: Vascular Pharmacology. 2012 ; Vol. 56, No. 1-2. pp. 56-63.
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