Type-Dependent Oxidative Damage Frontotemporal Lobar Degeneration: Cortical Astrocytes Are Targets of Oxidative Damage
Loading...
Date
2008
Authors
Martínez, Anna
Carmona, Margarita
Portero Otín, Manuel
Naudí i Farré, Alba
Pamplona Gras, Reinald
Ferrer, Isidre
Other authors
Impact
Export
Share
Journal Title
Journal ISSN
Volume Title
Abstract
Oxidative injury and stress responses are common features of
many neurodegenerative diseases. To assess oxidative stress responses
in frontotemporal lobar degeneration (FTLD), we identified
increased 4-hydroxynonenal (HNE) adducts using gel electrophoresis
and Western blotting in frontal cortex samples in 6 of 6 cases of
FTLD with the P301L mutation in the tau gene (FTLD-tau), in 3 of
10 cases with tau-negative ubiquitin-immunoreactive inclusions, and
in 2 of 3 cases associated with motor neuron disease. Selectively
increased lipoxidation-derived protein damage associated with altered
membrane unsaturation and fatty acid profiles was verified by
mass spectrometry in FTLD-tau and FTLD associated with motor
neuron disease. All FTLD-tau and most cases with increased HNEpositive
bands had marked astrocytosis as determined by glial
fibrillary acidic protein (GFAP) immunohistochemistry and
increased GFAP expression on Western blotting; 2 FTLD cases with
tau-negative ubiquitin-immunoreactive inclusions and with increased
GFAP expression did not have increased HNE adducts. Bidimensional
gel electrophoresis, Western blotting, in-gel digestion, and
mass spectrometry identified GFAP as a major target of lipoxidation
in all positive cases; confocal microscopy revealed colocalization of
HNE and GFAP in cortical astrocytes, superoxide dismutase 1 in
astrocytes, and superoxide dismutase 2 in astrocytes and neurons in
all FTLD types. Thus, in FTLD, there is variable disease-dependent
oxidative damage that is prominent in FTLD-tau, astrocytes are
targets of oxidative damage, and GFAP is a target of lipoxidation.
Astrocytes are, therefore, crucial elements of oxidative stress
responses in FTLD.
Citation
Journal or Serie
Journal of Neuropathology and Experimental Neurology, 2008, vol. 67, núm. 12, p. 1122-1136