Lipopolysaccharide and morphine-3-glucuronide-induced immune signalling increases the expression of polysialic acid in PC12 Cells

Sameera Iqbal, Lindsay M. Parker, Arun V. Everest Dass, Edward S. X. Moh, Nima Sayyadi, Mark R. Hutchinson, Nicolle H. Packer*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Polysialic acid (polySia), a long homopolymer of 2,8-linked sialic acids, is abundant in the embryonic brain and is restricted largely in adult brain to regions that exhibit neurogenesis and structural plasticity. In the central nervous system (CNS), polySia is highly important for cell-cell interactions, differentiation, migration and cytokine responses, which are critical neuronal functions regulating intercellular interactions that underlie immune signalling in the CNS. In recent reports, a metabolite of morphine, morphine-3-glucuronide (M3G), has been shown to cause immune signalling in the CNS. In this study, we compared the effects of neurite growth factor (NGF), lipopolysaccharide (LPS) and M3G exposure on the expression of polySia in PC12 cells using immunocytochemistry and Western blot analysis. PolySia was also extracted from stimulated cell proteins by endo-neuraminidase digestion and quantitated using fluorescent labelling followed by HPLC analysis. PolySia expression was significantly increased following NGF, M3G or LPS stimulation when compared with unstimulated cells or cells exposed to the TLR4 antagonist LPS-RS. Additionally, we analyzed the effects of test agent exposure on cell migration and the oxidative stress response of these cells in the presence and absence of polySia expression on their cell surface. We observed an increase in oxidative stress in cells without polySia as well as following M3G or LPS stimulation. Our study provides evidence that polySia expression in neuronal-like PC12 cells is influenced by M3G and LPS exposure alike, suggestive of a role of TLR4 in triggering these events.

Original languageEnglish
Pages (from-to)964-975
Number of pages12
JournalMolecular Neurobiology
Volume57
Issue number2
Early online date24 Oct 2019
DOIs
Publication statusPublished - Feb 2020

Keywords

  • Central nervous system
  • Glycans
  • Inflammation
  • Lipopolysaccharide (LPS)
  • Morphine-3-glucuronide (M3G)
  • Opioid
  • Polysialic acid
  • Sialic acids

Fingerprint Dive into the research topics of 'Lipopolysaccharide and morphine-3-glucuronide-induced immune signalling increases the expression of polysialic acid in PC12 Cells'. Together they form a unique fingerprint.

Cite this