Resveratrol inhibits high-glucose-induced inflammatory 'metabolic memory' in human retinal vascular endothelial cells through SIRT1-dependent signaling
| Autor: | Wenwen Chen, Qing Chang, Tingting Jiang, Junxiang Gu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cell Survival Physiology Inflammation AMP-Activated Protein Kinases Resveratrol Pharmacology Retina Cell Line 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Sirtuin 1 Physiology (medical) Diabetes mellitus medicine Humans Dose-Response Relationship Drug business.industry Endothelial Cells AMPK Retinal General Medicine medicine.disease Enzyme Activation Glucose 030104 developmental biology chemistry Cytoprotection High glucose medicine.symptom business 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Canadian Journal of Physiology and Pharmacology. 97:1141-1151 |
| ISSN: | 1205-7541 0008-4212 |
| Popis: | Diabetes induces vascular endothelial damage and this study investigated high-glucose-induced inflammation “metabolic memory” of human retinal vascular endothelial cells (HRVECs), the effects of resveratrol on HRVECs, and the underlying signaling. HRVECs were grown under various conditions and assayed for levels of sirtuin 1 (SIRT1); acetylated nuclear factor κB (Ac-NF-κB); NOD-like receptor family, pyrin domain containing 3 (NLRP3); and other inflammatory cytokines; and cell viability. A high glucose concentration induced HRVEC inflammation metabolic memory by decreasing SIRT1 and increasing Ac-NF-κB, NLRP3, caspase 1, interleukin-1β, inducible nitric oxide synthase, and tumor necrosis factor α, whereas exposure of HRVECs to a high glucose medium for 4 days, followed by a normal glucose concentration for an additional 4 days, failed to reverse these changes. A high glucose concentration also significantly reduced HRVEC viability. In contrast, resveratrol, a selective SIRT1 activator, markedly enhanced HRVEC viability and reduced the inflammatory cytokines expressions. In addition, high glucose reduced AMP-activated protein kinase (AMPK) phosphorylation and retained during the 4 days of the reversal period of culture. The effects of resveratrol were abrogated after co-treatment with the SIRT1 inhibitor nicotinamide and the AMPK inhibitor compound C. In conclusion, resveratrol was able to reverse high-glucose-induced inflammation “metabolic memory” of HRVECs by activation of the SIRT1/AMPK/NF-κB pathway. |
| Databáze: | OpenAIRE |
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