title: Pharmacological inhibition of HDAC6 attenuates endothelial barrier dysfunction induced by thrombin.
abstract: BACKGROUND
  Endothelial barrier dysfunction (EBD) involves microtubule disassembly and enhanced cell contractility. Histone deacetylase 6 (HDAC6) deacetylates α-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 (α-tubulin and acetylated α-tubulin) and contraction (phosphorylated myosin light chain 2, P-MLC2) were measured using immunoblots and immunofluorescence.
  
  
  CONCLUSIONS
  Thrombin induced a ∼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.
authors.affiliation: Department of Medicine, Tulane Medical School, New Orleans, LA, USA.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Saito
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Lasky
authors.forename: Weichao
authors.initials: W
authors.lastname: Guo
authors.forename: Hong
authors.initials: H
authors.lastname: Nguyen
authors.forename: Antonello
authors.initials: A
authors.lastname: Mai
authors.forename: Svitlana
authors.initials: S
authors.lastname: Danchuk
authors.forename: Deborah E
authors.initials: DE
authors.lastname: Sullivan
authors.forename: Bin
authors.initials: B
authors.lastname: Shan
mesh_terms: D000107:Acetylation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology*; D000073864:Histone Deacetylase 6; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D010539:Permeability; D011654:Pulmonary Edema / Q000201:enzymology*; D013917:Thrombin / Q000494:pharmacology
chemical_list: D056572:Histone Deacetylase Inhibitors; D013917:Thrombin; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases