Apamin Suppresses LPS-Induced Neuroinflammatory Responses by Regulating SK Channels and TLR4-Mediated Signaling Pathways

• Published in: International journal of molecular sciences Vol. 21; no. 12; p. 4319
• Main Authors: Park, Jihyun, Jang, Kyung Mi, Park, Kwan-Kyu
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17.06.2020; MDPI
• Subjects: Animals; apamin; Apamin - pharmacology; Ca2+/calmodulin-dependent protein kinase II; Calcium channels; Calcium conductance; CaMKII; Cell activation; Cell adhesion & migration; Channels; Cytokines; Cytokines - metabolism; Cytotoxicity; Deoxyribonucleic acid; Disease; Disease Susceptibility; DNA; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - metabolism; Inflammation; Inflammation Mediators - metabolism; Kinases; Lipopolysaccharides; Lipopolysaccharides - adverse effects; Localization; Lymphocytes B; MAP kinase; MAP Kinase Signaling System - drug effects; Mice; Microglia; Microglia - drug effects; Microglia - metabolism; Microglial cells; neuroinflammation; Neurological diseases; NF-kappa B - metabolism; NF-κB; NF-κB protein; Phosphorylation; Potassium channels; Potassium channels (calcium-gated); Potassium conductance; Proteins; Rats; Resistance; Signal transduction; Signal Transduction - drug effects; Small-Conductance Calcium-Activated Potassium Channels - metabolism; STAT3; Stat3 protein; STAT3 Transcription Factor - metabolism; TLR4; TLR4 protein; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Transcription; Transcription factors; Tumor necrosis factor-TNF; NF-κB; CaMKII; neuroinflammation; STAT3; MAPK-ERK; TLR4; apamin
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21124319

Neuroinflammation plays a vital role in neurodegenerative conditions. Microglia are a key component of the neuroinflammatory response. There is a growing interest in developing drugs to target microglia and thereby control neuroinflammatory processes. Apamin (APM) is a specifically selective antagonist of small conductance calcium-activated potassium (SK) channels. However, its effect on neuroinflammation is largely unknown. We examine the effects of APM on lipopolysaccharide (LPS)-stimulated BV2 and rat primary microglial cells. Regarding the molecular mechanism by which APM significantly inhibits proinflammatory cytokine production and microglial cell activation, we found that APM does so by reducing the expression of phosphorylated CaMKII and toll-like receptor (TLR4). In particular, APM potently suppressed the translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/signal transducer and activator of transcription (STAT)3 and phosphorylated mitogen-activated protein kinases (MAPK)-extracellular signal-regulated kinase (ERK). In addition, the correlation of NF-κB/STAT3 and MAPK-ERK in the neuroinflammatory response was verified through inhibitors. The literature and our findings suggest that APM is a promising candidate for an anti-neuroinflammatory agent and can potentially be used for the prevention and treatment of various neurological disorders.