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Histone deacetylase 3 (HDAC3), a member of class I HDAC, regulates a wide variety of normal and abnormal physiological functions. Recent experimental studies suggested that inhibition of HDAC3 may increase acetylation of certain key signaling regulating proteins such as peroxisome proliferator-activated receptor γ (PPARγ), which plays a crucial role in modulating cerebrovascular function and integrity. However, the role of HDAC3 inhibition in cerebrovascular endothelium function under pathological condition has not been fully investigated. In this study, we tested the hypothesis that inhibition of HDAC3 by RGFP966, a highly selective HDAC3 inhibitor, promotes PPARγ activation by enhancing its protein acetylation, resulting in protection of oxygen glucose deprivation and reoxygenation (OGD/R)-induced increase of transendothelial cell permeability. In cultured primary human brain microvascular endothelial cells, our experimental results show that OGD/R increases transendothelial cell permeability and down-regulates junction protein expression. While we also detected HDAC3 activity increase and PPARγ activity decline after OGD/R. However, treatment with RGFP966 significantly attenuated the OGD/R-induced increase of transendothelial cell permeability and down-regulation of tight junction protein Claudin-5. These effects were observed to be dependent on HDAC3 activity inhibition-mediated PPARγ protein acetylation/activation. Lastly, HDAC3 small interfering RNA mimics the protective effects of RGFP966 on human brain microvascular endothelial cells. Taken together, our data indicate that HDAC3 inhibition might comprise a new therapeutic target for reducing blood-brain barrier integrity disruption and vascular dysfunctions in neurological disorders.
Pubmed ID: 30347434 RIS Download
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This polyclonal targets acetyl Lysine antibody - ChIP Grade
View all literature mentionsThis polyclonal targets Claudin 5 antibody
View all literature mentionsThis monoclonal targets HDAC3
View all literature mentionsThis monoclonal targets beta-Actin (AC-15)
View all literature mentionsThis monoclonal targets alpha 1 Sodium Potassium ATPase antibody [464.6] - Plasma Membrane Marker
View all literature mentionsThis polyclonal targets Human VE Cadherin
View all literature mentionsThis monoclonal targets PPARγ
View all literature mentionsThis unknown targets
View all literature mentionsThis monoclonal targets Histone H3 (acetyl K9)
View all literature mentionsThis monoclonal targets Histone H3 (D1H2) XP Rabbit mAb
View all literature mentionsThis unknown targets Occludin
View all literature mentionsThis polyclonal targets HDAC6
View all literature mentionsThis unknown targets PPAR gamma
View all literature mentionsThis unknown targets ZO-1
View all literature mentionsThis monoclonal targets HDAC1 (10E2) Mouse mAb
View all literature mentionsThis monoclonal targets Histone H3 (acetyl K9)
View all literature mentionsThis polyclonal targets Human VE Cadherin
View all literature mentionsThis monoclonal targets alpha 1 Sodium Potassium ATPase antibody [464.6] - Plasma Membrane Marker
View all literature mentionsThis polyclonal targets acetyl Lysine antibody - ChIP Grade
View all literature mentionsThis monoclonal targets HDAC3
View all literature mentionsThis polyclonal targets Claudin 5 antibody
View all literature mentionsThis monoclonal targets Histone H3 (D1H2) XP Rabbit mAb
View all literature mentionsThis monoclonal targets PPARγ
View all literature mentionsThis polyclonal targets HDAC6
View all literature mentionsThis monoclonal targets beta-Actin (AC-15)
View all literature mentionsThis monoclonal targets HDAC1 (10E2) Mouse mAb
View all literature mentionsThis unknown targets Occludin
View all literature mentionsThis unknown targets ZO-1
View all literature mentionsThis unknown targets PPAR gamma
View all literature mentionsThis unknown targets
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