BIRC5 is a novel target of peroxisome proliferator-activated receptor γ in brain microvascular endothelium cells during cerebral ischemia

Abstract

Cerebral ischemia is a leading cause of ischemic stroke, which may lead to severe disability and mortality worldwide. There are some key factors concerned in cardioprotection, such as peroxisome proliferator-activated receptor γ (PPARγ), a ligand binding transcription factor involved in various biological functions including atherosclerosis, vascular dysfunction and hypertension, and baculoviral IAP repeat-containing 5(BIRC5), which may protect human brain endothelial cells from ischemia-induced apoptosis. To determine the potential roles of PPARγ in brain microvascular endothelial (bEnd.3) cells during cerebral ischemia and the relationship between PPARγ and BIRC5, a cerebral ischemia model was established with bEnd.3 cells cells by oxygen-glucose deprivation (OGD) treatment. OGD treatment reduced proliferation and enhanced apoptosis of bEnd.3 cells in a time-dependent manner. PPARγ expression levels were decreased in bEnd.3 cells following OGD treatment. Upregulation of PPARγ expression protected bEnd.3 cells from ischemia injury and also upregulated BIRC5 expression. PPARγ-specific binding sites in the BIRC5 promoter were predicted bioinformatically and verified by luciferase reporter experiments. Results from electrophoretic mobility shift/supershift and chromatin immunoprecipitation assays suggested that BIRC5 may be a novel target of PPARγ transcriptional regulation during ischemic injury. The present results indicated that PPARγ may serve a protective role on bEnd.3 cells and that BIRC5 may be a downstream target of PPARγ regulation during cerebral ischemia.