Arundic acid (ONO-2526) inhibits stimulated-S100B secretion in inflammatory conditions

• Published in: Neuroscience letters 2021-04, Vol.751, p.135776-135776, Article 135776
• Main Authors: Vizuete, Adriana Fernanda K., de Lima Cordeiro, Juliana, Neves, Juliana Dalibor, Seady, Marina, Grun, Lucas Kich, Barbé-Tuana, Florencia María, Leite, Marina Concli, Netto, Carlos Alexandre, Gonçalves, Carlos-Alberto
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Arundic acid; Astrocyte; Astrocytes - drug effects; Astrocytes - metabolism; Caprylates - pharmacology; Cells, Cultured; GFAP; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - metabolism; Lipopolysaccharides - toxicity; Male; Neuroinflammation; Neuroprotective Agents - pharmacology; Rats; Rats, Wistar; S100 Calcium Binding Protein beta Subunit - genetics; S100 Calcium Binding Protein beta Subunit - metabolism; S100B; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2021.135776

[Display omitted] •Neuroprotective activity of AA is based on changes in S100B synthesis.•We studied the effect of AA on S100B secretion in astrocytes and hippocampal slices.•AA inhibited LPS-stimulated S100B secretion in astrocyte cultures.•AA also inhibited TNF-α-stimulated S100B secretion by hippocampal slices.•Protection by AA under neuroinflammatory conditions may be mediated by decreased S100B secretion. Astrocytes respond to injury by modifying the expression profile of several proteins, including the S100 calcium-binding protein B (S100B), assumed to be a marker as well as a mediator of brain injury. AA is an inhibitor of S100B synthesis and plays a protective role in different models of brain injury, as decreases in S100B expression cause decreases in extracellular S100B. However, S100B mRNA expression, S100B protein content and S100B secretion do not always occur in association; as such, we herein investigated the effect of AA on S100B secretion, using different approaches with three stimulating conditions for S100B secretion, namely, low potassium medium, TNF-α (in hippocampal slices) and LPS exposure (in astrocyte cultures). Our data indicate that AA directly affects S100B secretion, indicating that the extracellular levels of this astroglial protein may be mediating the action of this compound. More importantly, AA had no effect on basal S100B secretion, but inhibited stimulated S100B secretion (stimulated either by the proinflammatory molecules, LPS or TNF-α, or by low potassium medium). Data from hippocampal slices that were directly exposed to AA, or from animals that received the acid by intracerebroventricular infusion, contribute to understanding its neuroprotective effect.