7,8-Dihydroxyflavone ameliorates high-glucose induced diabetic apoptosis in human retinal pigment epithelial cells by activating TrkB
| Autor: | Hong Liu, Xiaochuan Wang, Qiuhong Liu, Yan Wang, Xiaoyi Yu |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Biophysics Apoptosis Tropomyosin receptor kinase B Retinal Pigment Epithelium Pharmacology Biology 7 8-Dihydroxyflavone Biochemistry Cell Line 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Western blot medicine Humans Receptor trkB Molecular Biology Cells Cultured TUNEL assay Diabetic Retinopathy Membrane Glycoproteins medicine.diagnostic_test Dose-Response Relationship Drug virus diseases Epithelial Cells Cell Biology 030104 developmental biology Glucose chemistry 030220 oncology & carcinogenesis Immunology Flavanones Phosphorylation K252a Signal transduction Signal Transduction |
| Zdroj: | Biochemical and biophysical research communications. 495(1) |
| ISSN: | 1090-2104 |
| Popis: | Background In diabetic retinopathy, prolonged high-level blood glucose induced significant impairments among various retinal tissues, including retinal pigment epithelial (RPE) cells. In an in vitro model of human RPE cells, we evaluated whether 7,8-Dihydroxyflavone (DHF) may effectively prevent high glucose-induced diabetic apoptosis among human RPE cells. Method ARPE-19 cells, a Human RPE cell line, were treated with d -glucose (50 mM) to induce apoptosis in vitro. Prior to glucose, ARPE-19 cells were pre-incubated with various concentrations of DHF. The effect of DHF on d -glucose-induced apoptosis was examined by TUNEL assay, in a concentration-dependent manner. The biological effects of DHF on Caspase-9 (Casp-9) and TrkB signaling pathways in d -glucose-injured ARPE-19 cells were evaluated by qRT-PCR and western blot (WB) assays. A TrkB antagonist, K252a, was also applied in DHF and d -glucose treated ARPE-19 cells. Possible effect of K252a blocking TrkB signaling pathway, thus reversing DHF-modulated apoptosis prevention was also examined by TUNEL and WB assays. Results DHF ameliorated d -glucose-induced diabetic apoptosis in ARPE-19 cells. Apoptotic factor Casp-9, at both mRNA and protein levels, were drastically inhibited by DHF in d -glucose-injured ARPE-19 cells. Also, DHF activated TrkB signaling pathway through phosphorylation. K252a dramatically reversed the preventive effect of DHF on d -glucose-induced apoptosis in ARPE-19 cells. Further investigation showed that K252a functioned through de-activating or de-phosphorylating TrkB signaling pathway. Conclusion This work demonstrates that DHF, through activation of TrkB signaling pathway, has a preventive function in d -glucose-induced apoptosis in PRE cells in diabetic retinopathy. |
| Databáze: | OpenAIRE |
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