Abstract
AbstractBackgroundCerebral ischemic injury leads to over-activation of microglia, which release pro-inflammatory factors that deteriorate neurological function during the acute phase of stroke. Thus, inhibiting microglial over-activation is crucial for reducing ischemic injury. Sirtuin 1 (Sirt1) has been shown to play a critical role in stroke, neurodegenerative diseases and aging. However, the effect of Sirt1 on the regulation of microglial activation following cerebral ischemic injury, as well as the underlying mechanism, remain unknown. Therefore, the purpose of the present study is to mainly investigate the effect of Sirt1 on oxygen-glucose deprivation/reoxygenation (OGD/R)-treated N9 microglia following treatment with the Sirt1 agonists resveratrol and SRT1720 and the Sirt1 antagonist sirtinol.MethodsCell viability, Apoptosis, activation and inflammatory responses of microglia, expressions and activity of Shh signaling pathway proteins were detected by Cell Counting Kit 8, Flow Cytometry, immunocytochemistry, ELISA, and Western blotting, respectively.ResultsThe results demonstrated that treatment with resveratrol or SRT1720 could inhibit the activation of microglia and inflammation during OGD/R. Moreover, these treatments also led to the translocation of the GLI family zinc finger-1 (Gli-1) protein from the cytoplasm to the nucleus and upregulated the expression of Sonic hedgehog (Shh), Patched homolog-1 (Ptc-1), smoothened frizzled class receptor and Gli-1. By contrast, the inhibition of Sirt1 using sirtinol had the opposite effect.ConclusionThese findings suggested that Sirt1 may regulate microglial activation and inflammation by targeting the Shh/Gli-1 signaling pathway following OGD/R injury.Graphical abstract
Funder
National Nature Science Foundation of China
the Tibet Nature Science Foundation of Tibet
the Postgraduate Research and Innovation Project of Chongqing
Publisher
Springer Science and Business Media LLC
Subject
Genetics,Molecular Biology,General Medicine
Cited by
1 articles.
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