Document Detail

Taxol alleviates 2-methoxyestradiol-induced endothelial permeability.
MedLine Citation:
PMID:  22074808     Owner:  NLM     Status:  MEDLINE    
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.
Boris A Gorshkov; Marina A Zemskova; Alexander D Verin; Natalia V Bogatcheva
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-10-30
Journal Detail:
Title:  Vascular pharmacology     Volume:  56     ISSN:  1879-3649     ISO Abbreviation:  Vascul. Pharmacol.     Publication Date:    2012 Jan-Feb
Date Detail:
Created Date:  2012-01-30     Completed Date:  2012-08-21     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  101130615     Medline TA:  Vascul Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  56-63     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
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MeSH Terms
Acetylation / drug effects
Anilides / pharmacology
Capillary Permeability / drug effects*
Cells, Cultured
Drug Interactions
Endothelial Cells / drug effects*,  enzymology,  metabolism
Endothelium, Vascular / drug effects*,  enzymology,  metabolism
Estradiol / analogs & derivatives*,  pharmacology
HSP27 Heat-Shock Proteins / metabolism
Histone Deacetylases / metabolism
Hydroxamic Acids / pharmacology
Lung / drug effects,  metabolism
Mice, Inbred C57BL
Microtubules / metabolism
Myosin Light Chains / metabolism
Paclitaxel / pharmacology*
Phosphorylation / drug effects
Pulmonary Artery / drug effects,  enzymology,  metabolism
Tubulin / metabolism
p38 Mitogen-Activated Protein Kinases / metabolism
Grant Support
R01 HL-067307/HL/NHLBI NIH HHS; R01 HL-080675/HL/NHLBI NIH HHS; R01 HL-083327/HL/NHLBI NIH HHS; R01 HL067307/HL/NHLBI NIH HHS; R01 HL067307-08/HL/NHLBI NIH HHS; R01 HL080675/HL/NHLBI NIH HHS; R01 HL080675-04/HL/NHLBI NIH HHS; R01 HL083327/HL/NHLBI NIH HHS; R01 HL083327-05/HL/NHLBI NIH HHS
Reg. No./Substance:
0/2-methoxyoestradiol; 0/Anilides; 0/HSP27 Heat-Shock Proteins; 0/Hydroxamic Acids; 0/Myosin Light Chains; 0/Tubulin; 0/tubacin; 33069-62-4/Paclitaxel; 4TI98Z838E/Estradiol; EC Mitogen-Activated Protein Kinases; EC Deacetylases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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