Characterization of HDAC9 isoforms in brain microvessel bEnd.3 cells upon oxygen and glucose deprivation–reperfusion injury

Abstract

Histone deacetylases (HDACs) and their inhibitors affect the integrity of blood–brain barrier (BBB) which plays an important role in pathological conditions of the central nervous system (CNS). In this study, expression of HDACs was examined in bEnd.3 endothelial cells subjected to oxygen and glucose deprivation (OGD)–reperfusion injury. Expression of histone deacetylase-related protein (HDRP) produced by alternative splicing of HDAC9 was found to increase significantly in bEnd.3 cells upon OGD–reperfusion injury. HDRP was primarily localized in the nucleus. To investigate potential target genes of HDRP, its transcript was depleted by RNA interference and gene expression was determined. We found that FAS and GADD45a gene expression was up-regulated in HDRP-depleted bEnd.3 cells subjected to OGD–reperfusion injury. Interestingly, these genes are known to be involved in apoptosis and permeability of vascular endothelial cells. Our study suggests that HDRP may play a significant role in BBB integrity after CNS damage.