dc.contributor.author |
Martínez, Anna |
dc.contributor.author |
Carmona, Margarita |
dc.contributor.author |
Portero Otín, Manuel |
dc.contributor.author |
Naudí i Farré, Alba |
dc.contributor.author |
Pamplona Gras, Reinald |
dc.contributor.author |
Ferrer, Isidre |
dc.date |
2016-06-06T10:49:42Z |
dc.date |
2008 |
dc.date |
10000-01-01 |
dc.identifier |
0022-3069 |
dc.identifier |
http://hdl.handle.net/10459.1/57165 |
dc.identifier |
https://doi.org/10.1097/NEN.0b013e31818e06f3 |
dc.identifier.uri |
http://hdl.handle.net/10459.1/57165 |
dc.description |
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. |
dc.description |
This work was supported by Grants PI05/1570 and PI05/2214 from the Spanish Ministry of Health, Instituto de Salud Carlos III, and by Grant LSHM-CT-2004-503039 from the European Commission under the Sixth Framework Program (BrainNet Europe II) to Isidre Ferrer; by Grant BFU2006-14495/BFI from the Spanish Ministry of Education and Science, by Grant RD06/0013/0012 from the Spanish Ministry of Health (ISCIII, Red de Envejecimiento y Fragilidad), and by Grant 2005SGR00101 from the Autonomous Government of Catalonia to Reinald Pamplona; and by the Spanish Ministry of Health (Grants PI04/0355, PI05/2214, and PI05/2241), Spanish Ministry of Education and Science (Grant AGL2006-12433), B La Caixa[ Foundation, and COST B-35 Action to Manuel Portero-Otin. |
dc.language |
eng |
dc.publisher |
Oxford University Press |
dc.relation |
MIECI/PN2004-2007/BFU2006-14495/BFI |
dc.relation |
MIECI/PN2004-2007/AGL2006-12433 |
dc.relation |
Reproducció del document publicat a https://doi.org/10.1097/NEN.0b013e31818e06f3 |
dc.relation |
Journal of Neuropathology and Experimental Neurology, 2008, vol. 67, núm. 12, p. 1122-1136 |
dc.rights |
(c) American Association of Neuropathologists, Inc., 2008 |
dc.rights |
info:eu-repo/semantics/restrictedAccess |
dc.subject |
Astrocytes |
dc.subject |
Frontotemporal lobar degeneration |
dc.subject |
Hydroxynonenal |
dc.subject |
Malondialdehyde-lysine |
dc.title |
Type-Dependent Oxidative Damage Frontotemporal Lobar Degeneration: Cortical Astrocytes Are Targets of Oxidative Damage |
dc.type |
article |
dc.type |
publishedVersion |