Beta-synuclein displays an antiapoptotic p53-dependent phenotype and protects neurons from 6-hydroxydopamine-induced caspase 3 activation: cross-talk with alpha-synuclein and implication for Parkinson's disease.
Identifieur interne : 003086 ( Main/Exploration ); précédent : 003085; suivant : 003087Beta-synuclein displays an antiapoptotic p53-dependent phenotype and protects neurons from 6-hydroxydopamine-induced caspase 3 activation: cross-talk with alpha-synuclein and implication for Parkinson's disease.
Auteurs : Cristine Alves Da Costa [France] ; Eliezer Masliah ; Frédéric CheclerSource :
- The Journal of biological chemistry [ 0021-9258 ] ; 2003.
English descriptors
- KwdEn :
- Apoptosis, Caspase 3, Caspases (metabolism), Enzyme Activation, Humans, Nerve Tissue Proteins (physiology), Neurons (drug effects), Neuroprotective Agents, Oxidopamine (pharmacology), Parkinson Disease (etiology), Phenotype, Synucleins, Tumor Suppressor Protein p53 (analysis), Tumor Suppressor Protein p53 (physiology), alpha-Synuclein, beta-Synuclein.
- MESH :
- chemical , analysis : Tumor Suppressor Protein p53.
- chemical , metabolism : Caspases.
- chemical , pharmacology : Oxidopamine.
- chemical , physiology : Nerve Tissue Proteins, Tumor Suppressor Protein p53.
- chemical : Caspase 3, Neuroprotective Agents, Synucleins, alpha-Synuclein, beta-Synuclein.
- drug effects : Neurons.
- etiology : Parkinson Disease.
- Apoptosis, Enzyme Activation, Humans, Phenotype.
Abstract
We have established stable transfectants expressing beta-synuclein in TSM1 neurons. We show that in basal and staurosporine-induced conditions the number of terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling (TUNEL)-positive beta-synuclein-expressing neurons was drastically lower than in mock-transfected TSM1 cells. This was accompanied by a lower DNA fragmentation as evidenced by the reduction of propidium iodide incorporation measured by fluorescence-activated cell sorter analysis. beta-Synuclein strongly reduces staurosporine-induced caspase 3 activity and immunoreactivity. We establish that beta-synuclein triggers a drastic reduction of p53 expression and transcriptional activity. This was accompanied by increased Mdm2 immunoreactivity while p38 expression appeared enhanced, indicating that beta-synuclein-induced p53 down-regulation likely occurs at a post-transcriptional level. We showed previously that alpha-synuclein displays an antiapoptotic function that was abolished by the dopaminergic derived toxin 6-hydroxydopamine (6OHDA). Interestingly, beta-synuclein retains its ability to protect TSM1 neurons even after 6OHDA treatment. Furthermore, beta-synuclein restores the antiapoptotic function of alpha-synuclein in 6OHDA-treated neurons. Altogether, our data document for the first time that beta-synuclein protects neurons from staurosporine and 6OHDA-stimulated caspase activation in a p53-dependent manner. Our observation that beta-synuclein contributes to restoration of the alpha-synuclein antiapoptotic function abolished by 6OHDA may have direct implications for Parkinson's disease pathology. In this context, the cross-talk between these two parent proteins is discussed.
DOI: 10.1074/jbc.M306083200
PubMed: 12867415
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 001078
- to stream PubMed, to step Curation: 001037
- to stream PubMed, to step Checkpoint: 001037
- to stream Ncbi, to step Merge: 000350
- to stream Ncbi, to step Curation: 000350
- to stream Ncbi, to step Checkpoint: 000350
- to stream Main, to step Merge: 003556
- to stream Main, to step Curation: 003086
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Beta-synuclein displays an antiapoptotic p53-dependent phenotype and protects neurons from 6-hydroxydopamine-induced caspase 3 activation: cross-talk with alpha-synuclein and implication for Parkinson's disease.</title><author><name sortKey="Da Costa, Cristine Alves" sort="Da Costa, Cristine Alves" uniqKey="Da Costa C" first="Cristine Alves" last="Da Costa">Cristine Alves Da Costa</name><affiliation wicri:level="3"><nlm:affiliation>Institut de Pharmacologie Moléculaire et Cellulaire of Centre National de la Recherche Scientifique, UMR6097, 06560 Valbonne, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut de Pharmacologie Moléculaire et Cellulaire of Centre National de la Recherche Scientifique, UMR6097, 06560 Valbonne</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Valbonne</settlement></placeName></affiliation></author><author><name sortKey="Masliah, Eliezer" sort="Masliah, Eliezer" uniqKey="Masliah E" first="Eliezer" last="Masliah">Eliezer Masliah</name></author><author><name sortKey="Checler, Frederic" sort="Checler, Frederic" uniqKey="Checler F" first="Frédéric" last="Checler">Frédéric Checler</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2003">2003</date><idno type="RBID">pubmed:12867415</idno><idno type="pmid">12867415</idno><idno type="doi">10.1074/jbc.M306083200</idno><idno type="wicri:Area/PubMed/Corpus">001078</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001078</idno><idno type="wicri:Area/PubMed/Curation">001037</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001037</idno><idno type="wicri:Area/PubMed/Checkpoint">001037</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001037</idno><idno type="wicri:Area/Ncbi/Merge">000350</idno><idno type="wicri:Area/Ncbi/Curation">000350</idno><idno type="wicri:Area/Ncbi/Checkpoint">000350</idno><idno type="wicri:doubleKey">0021-9258:2003:Da Costa C:beta:synuclein:displays</idno><idno type="wicri:Area/Main/Merge">003556</idno><idno type="wicri:Area/Main/Curation">003086</idno><idno type="wicri:Area/Main/Exploration">003086</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Beta-synuclein displays an antiapoptotic p53-dependent phenotype and protects neurons from 6-hydroxydopamine-induced caspase 3 activation: cross-talk with alpha-synuclein and implication for Parkinson's disease.</title><author><name sortKey="Da Costa, Cristine Alves" sort="Da Costa, Cristine Alves" uniqKey="Da Costa C" first="Cristine Alves" last="Da Costa">Cristine Alves Da Costa</name><affiliation wicri:level="3"><nlm:affiliation>Institut de Pharmacologie Moléculaire et Cellulaire of Centre National de la Recherche Scientifique, UMR6097, 06560 Valbonne, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut de Pharmacologie Moléculaire et Cellulaire of Centre National de la Recherche Scientifique, UMR6097, 06560 Valbonne</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Valbonne</settlement></placeName></affiliation></author><author><name sortKey="Masliah, Eliezer" sort="Masliah, Eliezer" uniqKey="Masliah E" first="Eliezer" last="Masliah">Eliezer Masliah</name></author><author><name sortKey="Checler, Frederic" sort="Checler, Frederic" uniqKey="Checler F" first="Frédéric" last="Checler">Frédéric Checler</name></author></analytic><series><title level="j">The Journal of biological chemistry</title><idno type="ISSN">0021-9258</idno><imprint><date when="2003" type="published">2003</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Apoptosis</term><term>Caspase 3</term><term>Caspases (metabolism)</term><term>Enzyme Activation</term><term>Humans</term><term>Nerve Tissue Proteins (physiology)</term><term>Neurons (drug effects)</term><term>Neuroprotective Agents</term><term>Oxidopamine (pharmacology)</term><term>Parkinson Disease (etiology)</term><term>Phenotype</term><term>Synucleins</term><term>Tumor Suppressor Protein p53 (analysis)</term><term>Tumor Suppressor Protein p53 (physiology)</term><term>alpha-Synuclein</term><term>beta-Synuclein</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Tumor Suppressor Protein p53</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Caspases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Oxidopamine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Nerve Tissue Proteins</term><term>Tumor Suppressor Protein p53</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Caspase 3</term><term>Neuroprotective Agents</term><term>Synucleins</term><term>alpha-Synuclein</term><term>beta-Synuclein</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Neurons</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Apoptosis</term><term>Enzyme Activation</term><term>Humans</term><term>Phenotype</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We have established stable transfectants expressing beta-synuclein in TSM1 neurons. We show that in basal and staurosporine-induced conditions the number of terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling (TUNEL)-positive beta-synuclein-expressing neurons was drastically lower than in mock-transfected TSM1 cells. This was accompanied by a lower DNA fragmentation as evidenced by the reduction of propidium iodide incorporation measured by fluorescence-activated cell sorter analysis. beta-Synuclein strongly reduces staurosporine-induced caspase 3 activity and immunoreactivity. We establish that beta-synuclein triggers a drastic reduction of p53 expression and transcriptional activity. This was accompanied by increased Mdm2 immunoreactivity while p38 expression appeared enhanced, indicating that beta-synuclein-induced p53 down-regulation likely occurs at a post-transcriptional level. We showed previously that alpha-synuclein displays an antiapoptotic function that was abolished by the dopaminergic derived toxin 6-hydroxydopamine (6OHDA). Interestingly, beta-synuclein retains its ability to protect TSM1 neurons even after 6OHDA treatment. Furthermore, beta-synuclein restores the antiapoptotic function of alpha-synuclein in 6OHDA-treated neurons. Altogether, our data document for the first time that beta-synuclein protects neurons from staurosporine and 6OHDA-stimulated caspase activation in a p53-dependent manner. Our observation that beta-synuclein contributes to restoration of the alpha-synuclein antiapoptotic function abolished by 6OHDA may have direct implications for Parkinson's disease pathology. In this context, the cross-talk between these two parent proteins is discussed.</div></front></TEI><affiliations><list><country><li>France</li></country><region><li>Provence-Alpes-Côte d'Azur</li></region><settlement><li>Valbonne</li></settlement></list><tree><noCountry><name sortKey="Checler, Frederic" sort="Checler, Frederic" uniqKey="Checler F" first="Frédéric" last="Checler">Frédéric Checler</name><name sortKey="Masliah, Eliezer" sort="Masliah, Eliezer" uniqKey="Masliah E" first="Eliezer" last="Masliah">Eliezer Masliah</name></noCountry><country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Da Costa, Cristine Alves" sort="Da Costa, Cristine Alves" uniqKey="Da Costa C" first="Cristine Alves" last="Da Costa">Cristine Alves Da Costa</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonFranceV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 003086 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 003086 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonFranceV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:12867415
|texte= Beta-synuclein displays an antiapoptotic p53-dependent phenotype and protects neurons from 6-hydroxydopamine-induced caspase 3 activation: cross-talk with alpha-synuclein and implication for Parkinson's disease.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:12867415" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a ParkinsonFranceV1
| This area was generated with Dilib version V0.6.29. |  |