Advanced glycation endproducts are increased in the animal model of multiple sclerosis but cannot be reduced by pyridoxamine treatment or glyoxalase 1 overexpression

Suzan Wetzels, Kristiaan Wouters, Toshio Miyata, Jean L.J.M. Scheijen, Jerome J.A. Hendriks, Casper G. Schalkwijk, Tim Vanmierlo

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system (CNS). The immune response in MS patients leads to the infiltration of immune cells in the CNS and their subsequent activation. Immune cell activation induces a switch towards glycolysis. During glycolysis, the dicarbonyl product methylglyoxal (MGO) is produced. MGO is a glycating agent that can rapidly form advanced glycation endproducts (AGEs). In turn, AGEs are able to induce inflammatory responses. The glyoxalase system is the endogenous defense system of the body to reduce the burden of MGO thereby reducing AGE formation. This system consists of glyoxalase-1 and glyoxalase-2 which are able to detoxify MGO to D-lactate. We investigated whether AGE levels are induced in experimental autoimmune encephalitis (EAE), an inflammatory animal model of MS. Twenty seven days post EAE induction, MGO and AGE (Nε-(carboxymethyl)lysine (CML), Nε-(carboxyethyl)lysine (CEL), 5-hydro-5-methylimidazolone (MG-H1)) levels were significantly increased in the spinal cord of mice subjected to EAE. Yet, pyridoxamine treatment and glyoxalase-1 overexpression were unable to counteract AGE production during EAE and did not influence the clinical course of EAE. In conclusion, AGEs levels increase during EAE in the spinal cord, but AGE-modifying treatments do not inhibit EAE-induced AGE production and do not affect disease progression.

Original languageEnglish
Article number1311
JournalInternational journal of molecular sciences
Volume19
Issue number5
DOIs
Publication statusPublished - 2018 May

Keywords

  • Advanced glycation endproducts
  • Experimental autoimmune encephalomyelitis
  • Glyoxalase-1
  • Multiple sclerosis
  • Pyridoxamine

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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