Mitochondrial angiotensin receptors in dopaminergic neurons. Role in cell protection and aging-related vulnerability to neurodegeneration
Identifieur interne : 000234 ( Main/Exploration ); précédent : 000233; suivant : 000235Mitochondrial angiotensin receptors in dopaminergic neurons. Role in cell protection and aging-related vulnerability to neurodegeneration
Auteurs : Rita Valenzuela [Espagne] ; Maria A. Costa-Besada [Espagne] ; Javier Iglesias-Gonzalez [Royaume-Uni] ; Emma Perez-Costas [États-Unis] ; Bego A Villar-Cheda [Espagne] ; Pablo Garrido-Gil [Espagne] ; Miguel Melendez-Ferro [États-Unis] ; Ramon Soto-Otero [Espagne] ; Jose L. Lanciego [Espagne] ; Daniel Henrion [France] ; Rafael Franco [Espagne] ; Jose L. Labandeira-Garcia [Espagne]Source :
- Cell Death & Disease [ 2041-4889 ] ; 2016.
Abstract
The renin–angiotensin system (RAS) was initially considered as a circulating humoral system controlling blood pressure, being kidney the key control organ. In addition to the ‘classical' humoral RAS, a second level in RAS, local or tissular RAS, has been identified in a variety of tissues, in which local RAS play a key role in degenerative and aging-related diseases. The local brain RAS plays a major role in brain function and neurodegeneration. It is normally assumed that the effects are mediated by the cell-surface-specific G-protein-coupled angiotensin type 1 and 2 receptors (AT1 and AT2). A combination of
Url:
DOI: 10.1038/cddis.2016.327
PubMed: 27763643
PubMed Central: 5133991
Affiliations:
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Le document en format XML
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<country xml:lang="fr">États-Unis</country>
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<author><name sortKey="Villar Cheda, Bego A" sort="Villar Cheda, Bego A" uniqKey="Villar Cheda B" first="Bego A" last="Villar-Cheda">Bego A Villar-Cheda</name>
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<author><name sortKey="Garrido Gil, Pablo" sort="Garrido Gil, Pablo" uniqKey="Garrido Gil P" first="Pablo" last="Garrido-Gil">Pablo Garrido-Gil</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, CIMUS, University of Santiago de Compostela</institution>
, Santiago de Compostela,<country>Spain</country>
</nlm:aff>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Soto Otero, Ramon" sort="Soto Otero, Ramon" uniqKey="Soto Otero R" first="Ramon" last="Soto-Otero">Ramon Soto-Otero</name>
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, Santiago de Compostela,<country>Spain</country>
</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Lanciego, Jose L" sort="Lanciego, Jose L" uniqKey="Lanciego J" first="Jose L" last="Lanciego">Jose L. Lanciego</name>
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</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Henrion, Daniel" sort="Henrion, Daniel" uniqKey="Henrion D" first="Daniel" last="Henrion">Daniel Henrion</name>
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, Angers,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
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<author><name sortKey="Franco, Rafael" sort="Franco, Rafael" uniqKey="Franco R" first="Rafael" last="Franco">Rafael Franco</name>
<affiliation wicri:level="1"><nlm:aff id="aff9"><institution>Laboratory of Molecular Neurobiology, Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona</institution>
, Barcelona,<country>Spain</country>
</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Networking Research Center on Neurodegenerative Diseases (CIBERNED)</institution>
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</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea></wicri:regionArea>
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<author><name sortKey="Labandeira Garcia, Jose L" sort="Labandeira Garcia, Jose L" uniqKey="Labandeira Garcia J" first="Jose L" last="Labandeira-Garcia">Jose L. Labandeira-Garcia</name>
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, Santiago de Compostela,<country>Spain</country>
</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
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,<country>Madrid, Spain</country>
</nlm:aff>
<country xml:lang="fr">Espagne</country>
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<front><div type="abstract" xml:lang="en"><p>The renin–angiotensin system (RAS) was initially considered as a circulating humoral system controlling blood pressure, being kidney the key control organ. In addition to the ‘classical' humoral RAS, a second level in RAS, local or tissular RAS, has been identified in a variety of tissues, in which local RAS play a key role in degenerative and aging-related diseases. The local brain RAS plays a major role in brain function and neurodegeneration. It is normally assumed that the effects are mediated by the cell-surface-specific G-protein-coupled angiotensin type 1 and 2 receptors (AT1 and AT2). A combination of <italic>in vivo (rats, wild-type mice and</italic>
knockout <italic>mice)</italic>
and <italic>in vitro</italic>
(primary mesencephalic cultures, dopaminergic neuron cell line cultures) experimental approaches (confocal microscopy, electron microscopy, laser capture microdissection, transfection of fluorescent-tagged receptors, treatments with fluorescent angiotensin, western blot, polymerase chain reaction, HPLC, mitochondrial respirometry and other functional assays) were used in the present study. We report the discovery of AT1 and AT2 receptors in brain mitochondria, particularly mitochondria of dopaminergic neurons. Activation of AT1 receptors in mitochondria regulates superoxide production, via Nox4, and increases respiration. Mitochondrial AT2 receptors are much more abundant and increase after treatment of cells with oxidative stress inducers, and produce, via nitric oxide, a decrease in mitochondrial respiration. Mitochondria from the nigral region of aged rats displayed altered expression of AT1 and AT2 receptors. AT2-mediated regulation of mitochondrial respiration represents an unrecognized primary line of defence against oxidative stress, which may be particularly important in neurons with increased levels of oxidative stress such as dopaminergic neurons. Altered expression of AT1 and AT2 receptors with aging may induce mitochondrial dysfunction, the main risk factor for neurodegeneration.</p>
</div>
</front>
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</listBibl>
</div1>
</back>
</TEI>
<affiliations><list><country><li>Espagne</li>
<li>France</li>
<li>Royaume-Uni</li>
<li>États-Unis</li>
</country>
</list>
<tree><country name="Espagne"><noRegion><name sortKey="Valenzuela, Rita" sort="Valenzuela, Rita" uniqKey="Valenzuela R" first="Rita" last="Valenzuela">Rita Valenzuela</name>
</noRegion>
<name sortKey="Costa Besada, Maria A" sort="Costa Besada, Maria A" uniqKey="Costa Besada M" first="Maria A" last="Costa-Besada">Maria A. Costa-Besada</name>
<name sortKey="Costa Besada, Maria A" sort="Costa Besada, Maria A" uniqKey="Costa Besada M" first="Maria A" last="Costa-Besada">Maria A. Costa-Besada</name>
<name sortKey="Franco, Rafael" sort="Franco, Rafael" uniqKey="Franco R" first="Rafael" last="Franco">Rafael Franco</name>
<name sortKey="Franco, Rafael" sort="Franco, Rafael" uniqKey="Franco R" first="Rafael" last="Franco">Rafael Franco</name>
<name sortKey="Garrido Gil, Pablo" sort="Garrido Gil, Pablo" uniqKey="Garrido Gil P" first="Pablo" last="Garrido-Gil">Pablo Garrido-Gil</name>
<name sortKey="Garrido Gil, Pablo" sort="Garrido Gil, Pablo" uniqKey="Garrido Gil P" first="Pablo" last="Garrido-Gil">Pablo Garrido-Gil</name>
<name sortKey="Labandeira Garcia, Jose L" sort="Labandeira Garcia, Jose L" uniqKey="Labandeira Garcia J" first="Jose L" last="Labandeira-Garcia">Jose L. Labandeira-Garcia</name>
<name sortKey="Labandeira Garcia, Jose L" sort="Labandeira Garcia, Jose L" uniqKey="Labandeira Garcia J" first="Jose L" last="Labandeira-Garcia">Jose L. Labandeira-Garcia</name>
<name sortKey="Lanciego, Jose L" sort="Lanciego, Jose L" uniqKey="Lanciego J" first="Jose L" last="Lanciego">Jose L. Lanciego</name>
<name sortKey="Lanciego, Jose L" sort="Lanciego, Jose L" uniqKey="Lanciego J" first="Jose L" last="Lanciego">Jose L. Lanciego</name>
<name sortKey="Soto Otero, Ramon" sort="Soto Otero, Ramon" uniqKey="Soto Otero R" first="Ramon" last="Soto-Otero">Ramon Soto-Otero</name>
<name sortKey="Soto Otero, Ramon" sort="Soto Otero, Ramon" uniqKey="Soto Otero R" first="Ramon" last="Soto-Otero">Ramon Soto-Otero</name>
<name sortKey="Valenzuela, Rita" sort="Valenzuela, Rita" uniqKey="Valenzuela R" first="Rita" last="Valenzuela">Rita Valenzuela</name>
<name sortKey="Villar Cheda, Bego A" sort="Villar Cheda, Bego A" uniqKey="Villar Cheda B" first="Bego A" last="Villar-Cheda">Bego A Villar-Cheda</name>
<name sortKey="Villar Cheda, Bego A" sort="Villar Cheda, Bego A" uniqKey="Villar Cheda B" first="Bego A" last="Villar-Cheda">Bego A Villar-Cheda</name>
</country>
<country name="Royaume-Uni"><noRegion><name sortKey="Iglesias Gonzalez, Javier" sort="Iglesias Gonzalez, Javier" uniqKey="Iglesias Gonzalez J" first="Javier" last="Iglesias-Gonzalez">Javier Iglesias-Gonzalez</name>
</noRegion>
</country>
<country name="États-Unis"><noRegion><name sortKey="Perez Costas, Emma" sort="Perez Costas, Emma" uniqKey="Perez Costas E" first="Emma" last="Perez-Costas">Emma Perez-Costas</name>
</noRegion>
<name sortKey="Melendez Ferro, Miguel" sort="Melendez Ferro, Miguel" uniqKey="Melendez Ferro M" first="Miguel" last="Melendez-Ferro">Miguel Melendez-Ferro</name>
</country>
<country name="France"><noRegion><name sortKey="Henrion, Daniel" sort="Henrion, Daniel" uniqKey="Henrion D" first="Daniel" last="Henrion">Daniel Henrion</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>
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