Temporal dynamics of glyoxalase 1 in secondary neuronal injury.
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.
Department of Anatomy and Cell Biology, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany ; Institute of Anatomy, University of Leipzig, Leipzig, Germany.
Philipp
P
Pieroh
Institute of Anatomy, University of Leipzig, Leipzig, Germany.
Marco
M
Koch
Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany ; Translational Centre for Regenerative Medicine, Leipzig, Germany.
Daniel-Christoph
DC
Wagner
Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany ; Translational Centre for Regenerative Medicine, Leipzig, Germany ; Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
Johannes
J
Boltze
Institute of Anatomy, University of Leipzig, Leipzig, Germany.
Angela
A
Ehrlich
Department of Anatomy and Cell Biology, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany ; Institute of Anatomy, University of Leipzig, Leipzig, Germany.
Chalid
C
Ghadban
Institute of Anatomy, University of Leipzig, Leipzig, Germany.
Constance
C
Hobusch
Institute of Biochemistry, University of Leipzig, Leipzig, Germany.
Gerd
G
Birkenmeier
Department of Anatomy and Cell Biology, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany ; Institute of Anatomy, University of Leipzig, Leipzig, Germany.
Faramarz
F
Dehghani
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D015153:Blotting, Western; D001930:Brain Injuries / Q000378:metabolism* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D007150:Immunohistochemistry; D007791:Lactoylglutathione Lyase / Q000378:metabolism*; D018613:Microscopy, Confocal; D009474:Neurons / Q000378:metabolism*; D009924:Organ Culture Techniques; D011765:Pyruvaldehyde / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D011765:Pyruvaldehyde; D007791:Lactoylglutathione Lyase