Metformin increases phagocytosis and acidifies lysosomal/endosomal compartments in AMPK-dependent manner in rat primary microglia
- PMID: 20012266
- DOI: 10.1007/s00210-009-0477-x
Metformin increases phagocytosis and acidifies lysosomal/endosomal compartments in AMPK-dependent manner in rat primary microglia
Erratum in
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Erratum to: Metformin increases phagocytosis and acidifies lysosomal/endosomal compartments in AMPK-dependent manner in rat primary microglia.Naunyn Schmiedebergs Arch Pharmacol. 2017 Mar;390(3):329-330. doi: 10.1007/s00210-017-1350-y. Naunyn Schmiedebergs Arch Pharmacol. 2017. PMID: 28160018 No abstract available.
Abstract
Recent evidence suggests that metformin shows beneficial effects in experimental models of neuroinflammatory diseases. The aim of the present study was to determine the effect of metformin on phagocytosis and acidification of lysosomal/endosomal compartments in rat primary microglia in the presence of lipopolysaccharide (LPS) and/or beta-peptides (25-35), (1-40), and (1-42). Metformin increased the phagocytosis of fluorescent microspheres in the presence or absence of all the beta-peptides. However, the drug had no effect on the phagocytosis in LPS-stimulated microglia regardless of the presence of all the beta-peptides. Metformin acidified the lysosomal/endosomal compartments in the presence or absence of the beta-peptide 1-40 in both resting and activated microglia. To elucidate the mechanism of metformin action, we used 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside as an activator of adenosine monophosphate-activated protein kinase (AMPK) and compound C as a confirmed pharmacological inhibitor of AMPK. We have shown that metformin increased AMPK activity in microglial cells and that all observed effects are AMPK-dependent because the pretreatment of microglia with compound C reversed the effects of the drug. Since degradation of proteins in lysosomal/endosomal compartments depends largely on their phagocytosis and acidification, metformin may be beneficial in proteinopathies affecting the brain.
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