ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2020
AGK2 Alleviates Lipopolysaccharide Induced Neuroinflammation through Regulation of Mitogen-Activated Protein Kinase Phosphatase-1.
Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 29 citations in OpenAlex.
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- Epigenetic Regulation in Ischemic Neuroprotection: The Dual Role of HDACs and HATs in Neuroinflammation and Recovery.Antioxidants (Basel, Switzerland) · 2025Review
- Interaction Between Aging-Related Elastin-Derived Peptide (VGVAPG) and Sirtuin 2 and its Impact on Functions of Human Neuron Cells in an In Vitro Model.Molecular neurobiology · 2025Article
- Potential therapeutic targets for ischemic stroke in pre-clinical studies: Epigenetic-modifying enzymes DNMT/TET and HAT/HDAC.Frontiers in pharmacology · 2025Review
- Drugs Targeting Sirtuin 2 Exhibit Broad-Spectrum Anti-Infective Activity.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Down-regulation of MKP-1 in hippocampus protects against stress-induced depression-like behaviors and neuroinflammation.Translational psychiatry · 2024Article
- SIRT2 as a potential new therapeutic target for Alzheimer's disease.Neural regeneration research · 2024Review
- SIRT2 negatively regulates the cGAS-STING pathway by deacetylating G3BP1.EMBO reports · 2023Article
- SIRT2 Inhibition Rescues Neurodegenerative Pathology but Increases Systemic Inflammation in a Transgenic Mouse Model of Alzheimer's Disease.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023Article
- Sirtuin family in autoimmune diseases.Frontiers in immunology · 2023Review
- SIRT2 plays complex roles in neuroinflammation neuroimmunology-associated disorders.Frontiers in immunology · 2023Review
- Will Sirtuin 2 Be a Promising Target for Neuroinflammatory Disorders?Frontiers in cellular neuroscience · 2022Review
- Edaravone Dexborneol Alleviates Cerebral Ischemic Injury via MKP-1-Mediated Inhibition of MAPKs and Activation of Nrf2.BioMed research international · 2022Article
- Multiple Roles of SIRT2 in Regulating Physiological and Pathological Signal Transduction.Genetics research · 2022Review
- Sirtuins functions in central nervous system cells under neurological disorders.Frontiers in physiology · 2022Review
- Understanding the Potential Role of Sirtuin 2 on Aging: Consequences of SIRT2.3 Overexpression in Senescence.International journal of molecular sciences · 2021Article
- Role of SIRT1 in Hepatic Encephalopathy: In Vivo and In Vitro Studies Focusing on the NLRP3 Inflammasome.Oxidative medicine and cellular longevity · 2021Article
- Dexmedetomidine Ameliorates Hippocampus Injury and Cognitive Dysfunction Induced by Hepatic Ischemia/Reperfusion by Activating SIRT3-Mediated Mitophagy and Inhibiting Activation of the NLRP3 Inflammasome in Young Rats.Oxidative medicine and cellular longevity · 2020Article
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Authors and funding
8 authors at 1 institution in 1 country.
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Abstract
Neuroinflammation is associated with the progression of multiple neurological diseases. Many studies show that SIRT2 involves in multiple inflammatory processes. While, the mechanisms remain unclear. The purpose of this study was to explore the effect of SIRT2 inhibitor AGK2 on inflammatory responses and MAPK signaling pathways in LPS activated microglia in vitro and in vivo. The effect of AGK2 on cell viability of BV2 microglial cells was detected by CCK-8 assay. The expression of inflammatory cytokine iNOS was analyzed by western blotting and immunofluorescence. The mRNA expressions of iNOS, TNF-α, and IL-1β were detected by real-time polymerase chain reaction (RT-PCR). The SIRT2, phospho-P38, P38, phospho-JNK, JNK, phospho-ERK, ERK, α-tubulin, and acetyl-α-tubulin were analyzed by western blotting respectively. The interaction between SIRT2 and MKP-1 was measured by Co-immunoprecipitation (Co-IP) assay. Double immunofluorescent staining was performed to detect the expressions of CD11b and iNOS or SIRT2 in brain tissues. We found that AGK2 could suppress LPS-induced inflammatory cytokines (iNOS, TNF-α, and IL-1β) expression levels in BV2 microglial cells. Moreover, it could effectively reduce the expression of SIRT2 and increase the acetylation of α-tubulin in LPS activated BV2 microglial cells and LPS induced mice neuroinflammation. In addition, our results showed that AGK2 could reduce the increase of phosphorylation p38, JNK, and ERK after LPS challenge. Co-IP results showed that there was no direct interaction between MKP-1 and SIRT2. However, AGK2 by inhibition of SIRT2 could increase the expression of MKP-1. Furthermore, AGK2 could inhibit the activation of BV2 microglia and expression of iNOS and SIRT2 in LPS treated mice brain tissue. Taken together, our results suggested that AGK2 might alleviate lipopolysaccharide induced neuroinflammation through regulation of mitogen-activated protein kinase phosphatase-1. Graphical abstract.
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