Methylglyoxal reduces mitochondrial potential and activates Bax and caspase-3 in neurons: Implications for Alzheimer’s disease
Neuroscience Letters. 2014-09-01; 580: 78-82
DOI: 10.1016/j.neulet.2014.07.047
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1. Neurosci Lett. 2014 Sep 19;580:78-82. doi: 10.1016/j.neulet.2014.07.047. Epub
2014 Aug 4.
Methylglyoxal reduces mitochondrial potential and activates Bax and caspase-3 in
neurons: Implications for Alzheimer’s disease.
Tajes M(1), Eraso-Pichot A(1), Rubio-Moscardó F(1), Guivernau B(1), Bosch-Morató
M(1), Valls-Comamala V(1), Muñoz FJ(2).
Author information:
(1)Laboratory of Molecular Physiology and Channelopathies, Departament de
Ciències Experimentals i de la Salut (DCEXS), Universitat Pompeu Fabra (UPF),
Barcelona, Spain.
(2)Laboratory of Molecular Physiology and Channelopathies, Departament de
Ciències Experimentals i de la Salut (DCEXS), Universitat Pompeu Fabra (UPF),
Barcelona, Spain. Electronic address: .
Alzheimer’s disease (AD) is characterized by the oxidative stress generated from
amyloid β-peptide (Aβ) aggregates. It produces protein nitrotyrosination, after
the reaction with nitric oxide to form peroxynitrite, being triosephosphate
isomerase (TPI) one of the most affected proteins. TPI is a glycolytic enzyme
that catalyzes the interconversion between glyceraldehyde 3-phosphate (GAP) and
dihydroxyacetone phosphate (DHAP). Methylglyoxal (MG) is a by-product of TPI
activity whose production is triggered when TPI is nitrotyrosinated. MG is
harmful to cells because it glycates proteins. Here we found protein glycation
when human neuroblastoma cells were treated with Aβ. Moreover glycation was also
observed when neuroblastoma cells overexpressed mutated TPI where Tyr165 or
Tyr209, the two tyrosines close to the catalytic center, were changed by Phe in
order to mimic the effect of nitrotyrosination. The pathological relevance of
these findings was studied by challenging cells with Aβ oligomers and MG. A
significant decrease in mitochondrial transmembrane potential, one of the first
apoptotic events, was obtained. Therefore, increasing concentrations of MG were
assayed searching for MG effect in neuronal apoptosis. We found a decrease of the
protective Bcl2 and an increase of the proapoptotic caspase-3 and Bax levels. Our
results suggest that MG is triggering apoptosis in neurons and it would play a
key role in AD neurodegeneration.
Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
DOI: 10.1016/j.neulet.2014.07.047
PMID: 25102327 [Indexed for MEDLINE]