Temporal dynamics of glyoxalase 1 in secondary neuronal injury

PLoS One. 2014 Feb 3;9(2):e87364. doi: 10.1371/journal.pone.0087364. eCollection 2014.

Abstract

Background: Enhanced glycolysis leads to elevated levels of the toxic metabolite methylglyoxal which contributes to loss of protein-function, metabolic imbalance and cell death. Neurons were shown being highly susceptible to methylglyoxal toxicity. Glyoxalase 1 as an ubiquitous enzyme reflects the main detoxifying enzyme of methylglyoxal and underlies changes during aging and neurodegeneration. However, little is known about dynamics of Glyoxalase 1 following neuronal lesions so far.

Methods: To determine a possible involvement of Glyoxalase 1 in acute brain injury, we analysed the temporal dynamics of Glyoxalase 1 distribution and expression by immunohistochemistry and Western Blot analysis. Organotypic hippocampal slice cultures were excitotoxically (N-methyl-D-aspartate, 50 µM for 4 hours) lesioned in vitro (5 minutes to 72 hours). Additionally, permanent middle cerebral artery occlusion was performed (75 minutes to 60 days).

Results: We found (i) a predominant localisation of Glyoxalase 1 in endothelial cells in non-lesioned brains (ii) a time-dependent up-regulation and re-distribution of Glyoxalase 1 in neurons and astrocytes and (iii) a strong increase in Glyoxalase 1 dimers after neuronal injury (24 hours to 72 hours) when compared to monomers of the protein.

Conclusions: The high dynamics of Glyoxalase 1 expression and distribution following neuronal injury may indicate a novel role of Glyoxalase 1.

MeSH terms

  • Animals
  • Astrocytes / metabolism*
  • Blotting, Western
  • Brain Injuries / metabolism*
  • Brain Injuries / physiopathology
  • Endothelium, Vascular / metabolism
  • Hippocampus / metabolism*
  • Immunohistochemistry
  • Lactoylglutathione Lyase / metabolism*
  • Microscopy, Confocal
  • Neurons / metabolism*
  • Organ Culture Techniques
  • Pyruvaldehyde / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors

Substances

  • Pyruvaldehyde
  • Lactoylglutathione Lyase

Grants and funding

The authors have no support or funding to report.