Reduced sphingosine kinase-1 and enhanced sphingosine 1-phosphate lyase expression demonstrate deregulated sphingosine 1-phosphate signaling in Alzheimer’s disease
Identifieur interne : 003570 ( Main/Exploration ); précédent : 003569; suivant : 003571Reduced sphingosine kinase-1 and enhanced sphingosine 1-phosphate lyase expression demonstrate deregulated sphingosine 1-phosphate signaling in Alzheimer’s disease
Auteurs : Johnatan Ceccom [France] ; Najat Loukh [France] ; Valérie Lauwers-Cances [France] ; Christian Touriol [France] ; Yvan Nicaise [France] ; Catherine Gentil [France] ; Emmanuelle Uro-Coste [France] ; Stuart Pitson [Australie] ; Claude Alain Maurage [France] ; Charles Duyckaerts [France] ; Olivier Cuvillier [France] ; Marie-Bernadette Delisle [France]Source :
- Acta Neuropathologica Communications [ 2051-5960 ] ; 2014.
Abstract
The accumulation of beta amyloid (Aβ) peptides, a hallmark of Alzheimer’s disease (AD) is related to mechanisms leading to neurodegeneration. Among its pleiotropic cellular effects, Aβ accumulation has been associated with a deregulation of sphingolipid metabolism. Sphingosine 1-phosphate (S1P) derived from sphingosine is emerging as a critical lipid mediator regulating various biological activities including cell proliferation, survival, migration, inflammation, or angiogenesis. S1P tissue level is low and kept under control through equilibrium between its synthesis mostly governed by sphingosine kinase-1 (SphK1) and its degradation by sphingosine 1-phosphate lyase (SPL). We have previously reported that Aβ peptides were able to decrease the activity of SphK1 in cell culture models, an effect that could be blocked by the prosurvival IGF-1/IGF-1R signaling.
Herein, we report for the first time the expression of both SphK1 and SPL by immunohistochemistry in frontal and entorhinal cortices from 56 human AD brains. Immunohistochemical analysis revealed a decreased expression of SphK1 and an increased expression of SPL both correlated to amyloid deposits in the entorhinal cortex. Otherwise, analysis of brain tissue extracts showed a decrease of SphK1 expression in AD brains whereas SPL expression was increased. The content of IGF-1R, an activator of SphK1, was found decreased in AD brains as well as S1P1, the major receptor for S1P.
Collectively, these results highlight the importance of S1P in AD suggesting the existence of a global deregulation of S1P signaling in this disease from its synthesis by SphK1 and degradation by SPL to its signaling by the S1P1 receptor.
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DOI: 10.1186/2051-5960-2-12
PubMed: 24468113
PubMed Central: 3912487
Affiliations:
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wicri:level="3"><nlm:aff id="I1">CHU Toulouse, Service d’Anatomie Pathologique, 31059 Toulouse, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CHU Toulouse, Service d’Anatomie Pathologique, 31059 Toulouse</wicri:regionArea><placeName><region type="region" nuts="2">Occitanie (région administrative)</region><region type="old region" nuts="2">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="I2">Université de Toulouse III, Faculté de Médecine Rangueil, 31062 Toulouse, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université de Toulouse III, Faculté de Médecine Rangueil, 31062 Toulouse</wicri:regionArea><placeName><region type="region" nuts="2">Occitanie (région administrative)</region><region type="old region" nuts="2">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Loukh, Najat" sort="Loukh, Najat" uniqKey="Loukh N" first="Najat" last="Loukh">Najat Loukh</name><affiliation wicri:level="3"><nlm:aff id="I1">CHU Toulouse, Service d’Anatomie Pathologique, 31059 Toulouse, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CHU Toulouse, Service d’Anatomie Pathologique, 31059 Toulouse</wicri:regionArea><placeName><region type="region" nuts="2">Occitanie (région administrative)</region><region type="old region" nuts="2">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Lauwers Cances, Valerie" sort="Lauwers Cances, Valerie" uniqKey="Lauwers Cances V" first="Valérie" last="Lauwers-Cances">Valérie Lauwers-Cances</name><affiliation wicri:level="3"><nlm:aff id="I5">Service d’épidémiologie, CHU Toulouse, 31059 Toulouse, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Service d’épidémiologie, CHU Toulouse, 31059 Toulouse</wicri:regionArea><placeName><region type="region" nuts="2">Occitanie (région administrative)</region><region type="old region" nuts="2">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Touriol, Christian" sort="Touriol, Christian" uniqKey="Touriol C" first="Christian" last="Touriol">Christian Touriol</name><affiliation wicri:level="3"><nlm:aff id="I6">Inserm, UMR 1037, 31432 Toulouse, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Inserm, UMR 1037, 31432 Toulouse</wicri:regionArea><placeName><region type="region" nuts="2">Occitanie (région administrative)</region><region type="old region" nuts="2">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Nicaise, Yvan" sort="Nicaise, Yvan" uniqKey="Nicaise Y" first="Yvan" last="Nicaise">Yvan Nicaise</name><affiliation wicri:level="3"><nlm:aff id="I1">CHU Toulouse, Service d’Anatomie Pathologique, 31059 Toulouse, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CHU Toulouse, Service d’Anatomie Pathologique, 31059 Toulouse</wicri:regionArea><placeName><region type="region" nuts="2">Occitanie (région administrative)</region><region type="old region" nuts="2">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Gentil, Catherine" sort="Gentil, Catherine" uniqKey="Gentil C" first="Catherine" last="Gentil">Catherine Gentil</name><affiliation wicri:level="3"><nlm:aff id="I5">Service d’épidémiologie, CHU Toulouse, 31059 Toulouse, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Service d’épidémiologie, CHU Toulouse, 31059 Toulouse</wicri:regionArea><placeName><region type="region" nuts="2">Occitanie (région administrative)</region><region type="old region" nuts="2">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Uro Coste, Emmanuelle" sort="Uro Coste, Emmanuelle" uniqKey="Uro Coste E" first="Emmanuelle" last="Uro-Coste">Emmanuelle Uro-Coste</name><affiliation wicri:level="3"><nlm:aff id="I1">CHU Toulouse, Service d’Anatomie Pathologique, 31059 Toulouse, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CHU Toulouse, Service d’Anatomie Pathologique, 31059 Toulouse</wicri:regionArea><placeName><region type="region" nuts="2">Occitanie (région administrative)</region><region type="old region" nuts="2">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="I6">Inserm, UMR 1037, 31432 Toulouse, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Inserm, UMR 1037, 31432 Toulouse</wicri:regionArea><placeName><region type="region" nuts="2">Occitanie (région administrative)</region><region type="old region" nuts="2">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Pitson, Stuart" sort="Pitson, Stuart" uniqKey="Pitson S" first="Stuart" last="Pitson">Stuart Pitson</name><affiliation wicri:level="1"><nlm:aff id="I7">Centre for Cancer Biology, SA Pathology, Frome Road, Adelaide, SA 5000, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Cancer Biology, SA Pathology, Frome Road, Adelaide, SA 5000</wicri:regionArea><wicri:noRegion>SA 5000</wicri:noRegion></affiliation></author><author><name sortKey="Maurage, Claude Alain" sort="Maurage, Claude Alain" uniqKey="Maurage C" first="Claude Alain" last="Maurage">Claude Alain Maurage</name><affiliation wicri:level="1"><nlm:aff id="I8">Inserm, UMR 837, 59045 Lille, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Inserm, UMR 837, 59045 Lille</wicri:regionArea><wicri:noRegion>59045 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Recherche de l’ICM, Hôpital de la Salpétrière, 75013 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Neuropathologie et Centre de Recherche de l’ICM, Hôpital de la Salpétrière, 75013 Paris</wicri:regionArea><wicri:noRegion>75013 Paris</wicri:noRegion><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Cuvillier, Olivier" sort="Cuvillier, Olivier" uniqKey="Cuvillier O" first="Olivier" last="Cuvillier">Olivier Cuvillier</name><affiliation wicri:level="3"><nlm:aff id="I3">CNRS, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CNRS, Institut de Pharmacologie et de Biologie Structurale, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="I4">Université de Toulouse, UPS, IPBS, Toulouse, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université de Toulouse, UPS, IPBS, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Delisle, Marie Bernadette" sort="Delisle, Marie Bernadette" uniqKey="Delisle M" first="Marie-Bernadette" last="Delisle">Marie-Bernadette Delisle</name><affiliation wicri:level="1"><nlm:aff id="I1">CHU Toulouse, Service d’Anatomie Pathologique, 31059 Toulouse, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CHU Toulouse, Service d’Anatomie Pathologique, 31059 Toulouse</wicri:regionArea><wicri:noRegion>31059 Toulouse</wicri:noRegion><placeName><settlement type="city">Toulouse</settlement><region type="region" nuts="2">Occitanie (région administrative)</region><region type="old region" nuts="2">Midi-Pyrénées</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="I6">Inserm, UMR 1037, 31432 Toulouse, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Inserm, UMR 1037, 31432 Toulouse</wicri:regionArea><wicri:noRegion>31432 Toulouse</wicri:noRegion><placeName><settlement type="city">Toulouse</settlement><region type="region" nuts="2">Occitanie (région administrative)</region><region type="old region" nuts="2">Midi-Pyrénées</region></placeName></affiliation></author></analytic><series><title level="j">Acta Neuropathologica Communications</title><idno type="eISSN">2051-5960</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>The accumulation of beta amyloid (Aβ) peptides, a hallmark of Alzheimer’s disease (AD) is related to mechanisms leading to neurodegeneration. Among its pleiotropic cellular effects, Aβ accumulation has been associated with a deregulation of sphingolipid metabolism. Sphingosine 1-phosphate (S1P) derived from sphingosine is emerging as a critical lipid mediator regulating various biological activities including cell proliferation, survival, migration, inflammation, or angiogenesis. S1P tissue level is low and kept under control through equilibrium between its synthesis mostly governed by sphingosine kinase-1 (SphK1) and its degradation by sphingosine 1-phosphate lyase (SPL). We have previously reported that Aβ peptides were able to decrease the activity of SphK1 in cell culture models, an effect that could be blocked by the prosurvival IGF-1/IGF-1R signaling.</p></sec><sec><title>Results</title><p>Herein, we report for the first time the expression of both SphK1 and SPL by immunohistochemistry in frontal and entorhinal cortices from 56 human AD brains. Immunohistochemical analysis revealed a decreased expression of SphK1 and an increased expression of SPL both correlated to amyloid deposits in the entorhinal cortex. Otherwise, analysis of brain tissue extracts showed a decrease of SphK1 expression in AD brains whereas SPL expression was increased. The content of IGF-1R, an activator of SphK1, was found decreased in AD brains as well as S1P<sub>1</sub>, the major receptor for S1P.</p></sec><sec><title>Conclusions</title><p>Collectively, these results highlight the importance of S1P in AD suggesting the existence of a global deregulation of S1P signaling in this disease from its synthesis by SphK1 and degradation by SPL to its signaling by the S1P<sub>1</sub> receptor.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Duyckaerts, C" uniqKey="Duyckaerts C">C Duyckaerts</name></author><author><name sortKey="Delatour, B" uniqKey="Delatour B">B Delatour</name></author><author><name sortKey="Potier, Mc" uniqKey="Potier M">MC Potier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nelson, Pt" uniqKey="Nelson P">PT Nelson</name></author><author><name sortKey="Alafuzoff, I" uniqKey="Alafuzoff I">I Alafuzoff</name></author><author><name 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Brinkmann</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Australie</li><li>France</li></country><region><li>Midi-Pyrénées</li><li>Occitanie (région administrative)</li><li>Île-de-France</li></region><settlement><li>Paris</li><li>Toulouse</li></settlement></list><tree><country name="France"><region name="Occitanie (région administrative)"><name sortKey="Ceccom, Johnatan" sort="Ceccom, Johnatan" uniqKey="Ceccom J" first="Johnatan" last="Ceccom">Johnatan Ceccom</name></region><name sortKey="Ceccom, Johnatan" sort="Ceccom, Johnatan" uniqKey="Ceccom J" first="Johnatan" last="Ceccom">Johnatan Ceccom</name><name sortKey="Cuvillier, Olivier" sort="Cuvillier, Olivier" uniqKey="Cuvillier O" first="Olivier" last="Cuvillier">Olivier Cuvillier</name><name sortKey="Cuvillier, Olivier" sort="Cuvillier, Olivier" uniqKey="Cuvillier O" first="Olivier" last="Cuvillier">Olivier Cuvillier</name><name sortKey="Delisle, Marie Bernadette" sort="Delisle, Marie Bernadette" uniqKey="Delisle M" first="Marie-Bernadette" last="Delisle">Marie-Bernadette Delisle</name><name sortKey="Delisle, Marie Bernadette" sort="Delisle, Marie Bernadette" uniqKey="Delisle M" first="Marie-Bernadette" last="Delisle">Marie-Bernadette Delisle</name><name sortKey="Duyckaerts, Charles" sort="Duyckaerts, Charles" uniqKey="Duyckaerts C" first="Charles" last="Duyckaerts">Charles Duyckaerts</name><name sortKey="Gentil, Catherine" sort="Gentil, Catherine" uniqKey="Gentil C" first="Catherine" last="Gentil">Catherine Gentil</name><name sortKey="Lauwers Cances, Valerie" sort="Lauwers Cances, Valerie" uniqKey="Lauwers Cances V" first="Valérie" last="Lauwers-Cances">Valérie Lauwers-Cances</name><name sortKey="Loukh, Najat" sort="Loukh, Najat" uniqKey="Loukh N" first="Najat" last="Loukh">Najat Loukh</name><name sortKey="Maurage, Claude Alain" sort="Maurage, Claude Alain" uniqKey="Maurage C" first="Claude Alain" last="Maurage">Claude Alain Maurage</name><name sortKey="Maurage, Claude Alain" sort="Maurage, Claude Alain" uniqKey="Maurage C" first="Claude Alain" last="Maurage">Claude Alain Maurage</name><name sortKey="Maurage, Claude Alain" sort="Maurage, Claude Alain" uniqKey="Maurage C" first="Claude Alain" last="Maurage">Claude Alain Maurage</name><name sortKey="Nicaise, Yvan" sort="Nicaise, Yvan" uniqKey="Nicaise Y" first="Yvan" last="Nicaise">Yvan Nicaise</name><name sortKey="Touriol, Christian" sort="Touriol, Christian" uniqKey="Touriol C" first="Christian" last="Touriol">Christian Touriol</name><name sortKey="Uro Coste, Emmanuelle" sort="Uro Coste, Emmanuelle" uniqKey="Uro Coste E" first="Emmanuelle" last="Uro-Coste">Emmanuelle Uro-Coste</name><name sortKey="Uro Coste, Emmanuelle" sort="Uro Coste, Emmanuelle" uniqKey="Uro Coste E" first="Emmanuelle" last="Uro-Coste">Emmanuelle Uro-Coste</name></country><country name="Australie"><noRegion><name sortKey="Pitson, Stuart" sort="Pitson, Stuart" uniqKey="Pitson S" first="Stuart" 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| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a AustralieFrV1
| This area was generated with Dilib version V0.6.33. |  |