4‐O‐carboxymethylascochlorin protected against microglial‐mediated neurotoxicity in SH‐SY5Y and BV2 cocultured cells from LPS–induced neuroinflammation and death by inhibiting MAPK, NF‐κB, and Akt pathways. Issue 2 (15th October 2018)

• Record Type: Journal Article
• Authors: Park, Junyoung; Ha, Sun‐Hyung; Abekura, Fukushi; Lim, Hakseong; Chang, Young‐Chae; Lee, Moon‐Jo; Lee, Miri; Lee, Young‐Choon; Kim, Cheorl‐Ho
• Is Part Of: Journal of cellular biochemistry. Volume 120:Issue 2(2019)
• Page Start: 1742
• Page End: 1753
• Publication Date: 2018-10-15
• Subjects: 4‐O‐carboxymethylascochlorin (AS‐6) -- BV‐2 microglia cells -- lipopolysaccharide (LPS) -- neuroinflammation -- neurotoxicity; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.27464
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: In our previous studies, structurally similar compounds of ascochlorin and ascofuranone exhibited anti‐inflammatory activity. Neural inflammation plays a significant role in the commence and advancement of neurodegenerative diseases. It is not known whether 4‐O‐carboxymethylascochlorin (AS‐6) regulates the initial stage of inflammatory responses at the cellular level in BV2 microglia cells. We here investigated the anti‐inflammatory effects of AS‐6 treatment in microglia cells with the microglial protection in neurons. We found that the lipopolysaccharide (LPS)‐stimulated production of nitric oxide, a main regulator of inflammation, is suppressed by AS‐6 in BV2 microglial cells. In addition, AS‐6 dose‐dependently suppressed the increase in COX‐2 protein and messenger RNA levels in LPS‐stimulated BV2 cells. Moreover, AS‐6 inhibited the expression and secretion of proinflammatory cytokines in BV2 microglial cells. At the intracellular level, AS‐6 inhibited LPS‐activated nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) in BV2 microglial cells. AS‐6 negatively affected mitogen‐activated protein kinases (MAPK) and Akt phosphorylation: Phosphorylated forms of ERK, JNK, p38, and Akt decreased. To check whether AS‐6 protects against inflammatory inducer‐mediated neurotoxicity, neuronal SH‐SY5Y cells were coincubated with BV2 cells in conditioned medium. AS‐6 exerted a neuroprotective effect by suppressing microglial activation by LPS or amyloid‐β peptide. AS‐6 is a promising suppressor of inflammatory responses in LPS‐induced BV2 cells by attenuating NF‐κB and MAPKs signaling. AS‐6 protected against microglial‐mediated neurotoxicity in SH‐SY5Y and BV2 cocultured cells from LPS–induced neuroinflammation and death via inhibiting MAPK, NF‐κB, and Akt pathways. Abstract : 4‐O‐carboxymethylascochlorin (AS‐6) protects cocultured neuronal SH‐SY5Y and BV2 microglia cells from inflammation‐induced death and inhibited the inflammatory response in BV2 microglia cells through suppression of nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB), p‐ERK1/2, p‐JNK, p‐p38, p‐Akt, tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), and IL‐6.