Induction of Autophagy and Activation of SIRT‐1 Deacetylation Mechanisms Mediate Neuroprotection by the Pomegranate Metabolite Urolithin A in BV2 Microglia and Differentiated 3D Human Neural Progenitor Cells
| Autor: | Olumayokun A. Olajide, Izabela Lepiarz, Ravikanth Velagapudi, Folashade O. Katola, Bernd L. Fiebich, Harsharan S. Bhatia, Abdelmeneim El-Bakoush |
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| Rok vydání: | 2019 |
| Předmět: |
Lipopolysaccharides
0301 basic medicine Cell Culture Techniques Neuroprotection Mice 03 medical and health sciences chemistry.chemical_compound Neural Stem Cells Sirtuin 1 Coumarins Autophagy medicine Animals Humans Neuroinflammation Lythraceae Amyloid beta-Peptides 030109 nutrition & dietetics Microglia biology Chemistry NF-kappa B Acetylation Cell Differentiation Urolithin Cell biology Neuroprotective Agents 030104 developmental biology medicine.anatomical_structure Sirtuin biology.protein Tumor necrosis factor alpha Food Science Biotechnology Ellagic acid |
| Zdroj: | Molecular Nutrition & Food Research. 63:1801237 |
| ISSN: | 1613-4133 1613-4125 |
| DOI: | 10.1002/mnfr.201801237 |
| Popis: | Scope Urolithin A is an anti-inflammatory and neuroprotective gut-derived metabolite from ellagitannins and ellagic acid in pomegranate, berries, and nuts. The roles of SIRT-1 and autophagy in the neuroprotective activity of urolithin A are investigated. Methods and results Analyses of culture supernatants from lipopolysaccharide-stimulated BV2 microglia show that urolithin A (2.5-10 µm) produced significant reduction in the production of nitrite, tumor necrosis factor (TNF)-α and IL-6. The anti-inflammatory effect of the compound is reversed in the presence of sirtuin (SIRT)-1 and the autophagy inhibitors EX527 and chloroquine, respectively. Protein analyses reveal reduction in p65 and acetyl-p65 protein. Treatment of BV2 microglia with urolithin A results in increased SIRT-1 activity and nuclear protein, while induction of autophagy by the compound is demonstrated using autophagy fluorescent and autophagy LC3 HiBiT reporter assays. Viability assays reveal that urolithin A produces a neuroprotective effect in APPSwe-transfected ReNcell VM human neural cells, which is reversed in the presence of EX527 and chloroquine. Increase in both SIRT-1 and autophagic activities are also detected in these cells following treatment with urolithin A. Conclusions It has been proposed that SIRT-1 activation and induction of autophagy are involved in the neuroprotective activity of urolithin A in brain cells. |
| Databáze: | OpenAIRE |
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