Abstract
ObjectiveThe aim of this study was to investigate the effects of docosahexaenoic acid (DHA) on the generation of angiopoietin-2 (Ang-2) by rat brain microvascular endothelial cells under an oxygen- and glucose-deprivation environment (OGD), and its relationship, if any, with cyclooxygenase 2 (COX-2) expression.MethodsAnnexin V and propidium iodide apoptosis assay was used to detect apoptosis. Enzyme linked immunosorbent assay was used to detect Ang-2, vascular endothelial growth factor (VEGF), prostaglandin E2 (PGE2), and prostaglandin I2 (PGI2) content. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect Ang-2 and VEGF mRNA expression. Western blot was used to detect expression of COX-2 protein.ResultsDHA reduced the apoptosis rate (P = 0.026) and decreased the secretion of Ang-2, VEGF, PGE2, and PGI2 (P = 0.006, P = 0.000, P = 0.002, P = 0.004 respectively). The relative expression of Ang2 and Vegf mRNA, as well as COX-2 expression, also decreased (P = 0.000, P = 0.005, P = 0.007 respectively). These effects were antagonized by GW9662 (peroxisome proliferator-activated receptor-γ antagonist). COX-2 protein expression levels were positively correlated with Ang2 and Vegf mRNA expression levels (γ = 0.69, P = 0.038 and γ = 0.76, P = 0.032, respectively). Ang-2 and VEGF mRNA levels were positively correlated with Ang-2 (γ = 0.84, P = 0.012) and VEGF (γ = 0.71, P = 0.036) secretion levels respectively.ConclusionDHA reduced apoptosis induced by an OGD environment, thus decreasing Ang-2 and VEGF synthesis. This phenomenon was associated with a decrease in COX-2 protein expression, PGE2 and PGI2 secretion, and generation regulation via intracellular transcriptional pathways.
Highlights
Studies have confirmed that the angiopoietin (Ang)-Tie2 signaling pathway is related with functional recovery and prognosis after brain injury (Wang et al 2015; ChittiboinaChen et al SpringerPlus (2016) 5:1518 et al 2013; Fischer et al 2011)
Apoptosis in brain microvascular endothelial cells (BMVEC) Apoptosis in BMVECs of the oxygen- and glucose-deprivation environment (OGD), OGD + 10 μM docosahexaenoic acid (DHA), OGD + 40 μM DHA, OGD + 10 μM DHA + GW9662, and OGD + 40 μM DHA + GW9662 groups increased significantly compared with the control group (P < 0.01)
Secretion of Ang‐2, vascular endothelial growth factor (VEGF), prostaglandin E2 (PGE2), and prostaglandin I2 (PGI2) Compared with the normal control group, Ang-2, VEGF, PGE2, and PGI2 secretion levels of the OGD, OGD +10 μM DHA, OGD + 40 μM DHA, OGD + 10 μM DHA GW9662, and OGD + 40 μM DHA + GW9662 groups were significantly increased (P < 0.01)
Summary
Studies have confirmed that the angiopoietin (Ang)-Tie signaling pathway is related with functional recovery and prognosis after brain injury (Wang et al 2015; ChittiboinaChen et al SpringerPlus (2016) 5:1518 et al 2013; Fischer et al 2011). Studies have confirmed that the angiopoietin (Ang)-Tie signaling pathway is related with functional recovery and prognosis after brain injury Ang-1 is constitutively produced by pericytes and can be induced in several perivascular cell types. In the early stages of brain injury, Ang-2 expression rapidly increases, whereas Ang-1 amounts decrease. Tie-2 phosphorylation can increase the expression of phosphoinositide 3-kinase (PI3 K)Akt signaling pathway proteins, which has been closely linked to cell survival, as well as the expression of endothelial composite materials and endothelial cell gap junction stabilization (Hill et al 2014; Yu et al 2012; Ruan and Kazlauskas 2013). During early ischemia, the intervention and regulation of the Ang/Tie signaling pathway by increasing Ang-1 or decreasing Ang-2 levels may be an effective strategy for protecting the brain
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