Metabolomic analysis revealed glycylglycine accumulation in astrocytes after methionine enkephalin administration exhibiting neuron protective effects

J Pharm Biomed Anal. 2015 Nov 10:115:48-54. doi: 10.1016/j.jpba.2015.06.028. Epub 2015 Jun 24.

Abstract

Owing to its unrevealed etiology, multiple sclerosis lacks specific therapies up to now. Experiential administration of methionine enkephalin (MENK) on mouse model improved disease manifestations to some extent. In order to gain more insight on the significance of MENK application, a capillary electrophoresis-mass spectrometry (CE-MS) technique was employed to profile intracellular metabolite fluctuation in 5 astrocytoma cell lines challenged by MENK. The processed data were first evaluated through a bioinformatic process to ensure their compatibility with the study aims and then subjected to multivariate analysis. The results indicated that MENK administration increased intracellular tyrosine, phenylalanine, methionine and glycylglycine. Exemplified by U87 cells, glycylglycine inhibited cell proliferation as well as MENK but it also decreased cell nitric oxide excretion which could not be evoked by MENK. The neuron protective effects were also mirrored by the increased expression of some genes related to remyelination. This study demonstrated CE-MS to be a promising tool for cell metabolomic analysis and benefited the therapeutic exploring of multiple sclerosis with respect to metabolism intervention.

Keywords: Capillary electrophoresis-mass spectrometry; Metabolomics; Methionine enkephalin; Multiple sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / drug effects*
  • Astrocytes / immunology
  • Astrocytes / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cluster Analysis
  • Cytokines / genetics
  • Electrophoresis, Capillary
  • Enkephalin, Methionine / pharmacology*
  • Glycylglycine / metabolism*
  • Glycylglycine / pharmacology
  • Humans
  • Mass Spectrometry
  • Metabolomics / instrumentation
  • Metabolomics / methods*
  • Multiple Sclerosis / metabolism
  • Multivariate Analysis
  • Neurons / drug effects*
  • Neuroprotective Agents / pharmacology*
  • Nitric Oxide / metabolism
  • Rats
  • Receptors, Opioid / metabolism

Substances

  • Cytokines
  • Neuroprotective Agents
  • Receptors, Opioid
  • methionine-enkephalin receptor
  • Glycylglycine
  • Nitric Oxide
  • Enkephalin, Methionine