Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 408, Issue 4, Pages 630-634Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2011.04.075
Keywords
HDAC6; Endothelial barrier; Thrombin
Categories
Funding
- NIH [HL083480, CA132603]
- Louisiana Board of Regents [LEQSF(2008-10)-RD-A-26]
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Background: Endothelial barrier dysfunction (EBD) involves microtubule disassembly and enhanced cell contractility. Histone deacetylase 6 (HDAC6) deacetylates alpha-tubulin, and thereby destabilizes microtubules. This study investigates a role for HDAC6 in EBD. Methods: EBD was induced with thrombin +/- HDAC6 inhibitors (tubacin and MC1575), and assessed by transendothelial electrical resistance (TEER). Markers for microtubule disassembly (alpha-tubulin and acetylated alpha-tubulin) and contraction (phosphorylated myosin light chain 2, P-MLC2) were measured using immunoblots and immunofluorescence. Results and conclusion: Thrombin induced a similar to 50% decrease in TEER that was abrogated by the HDAC6 inhibitors. Moreover, inhibition of HDAC6 diminished edema in the lung injured by lipopolysaccharide. Lastly, inhibition of HDAC6 attenuated thrombin-induced microtubule disassembly and P-MLC2. Our results suggest that HDAC6 can be targeted to limit EBD. (C) 2011 Elsevier Inc. All rights reserved.
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