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Updated: Jun 2, 2026
Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS
Published on: August 10, 2017
Pharmacological inhibition of HDAC6 attenuates endothelial barrier dysfunction induced by thrombin
Shigeki Saito1, Joseph A Lasky, Weichao Guo
1Department of Medicine, Tulane Medical School, New Orleans, LA, USA.
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.
Results And Conclusion:
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.
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