Upregulation of protease-activated receptor-1 in astrocytes in parkinson disease : Astrocyte-mediated neuroprotection through increased levels of glutathione peroxidase
Identifieur interne : 002892 ( Main/Exploration ); précédent : 002891; suivant : 002893Upregulation of protease-activated receptor-1 in astrocytes in parkinson disease : Astrocyte-mediated neuroprotection through increased levels of glutathione peroxidase
Auteurs : Yuri Ishida [Japon] ; Atsushi Nagai [Japon] ; Shotai Kobayashi [Japon] ; Seung U. Kim [Corée du Sud, Canada]Source :
- Journal of neuropathology and experimental neurology [ 0022-3069 ] ; 2006.
Descripteurs français
- Pascal (Inist)
English descriptors
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Abstract
In the present study, we investigated the expression of protease-activated receptors (PARs), receptors for thrombin, in substantia nigra pars compacta (SNpc) of Parkinson disease (PD) brains and cultures of human neurons, astrocytes, oligodendrocytes, and microglia as determined by immunocytochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). Expression of PAR-1 was demonstrated only in glial fibrillary acidic protein-positive astrocytes in SNpc, and the number of astrocytes expressing PAR-1 increased in SNpc of PD as compared with nonneurologic control brain. Immunoreactivity for thrombin and prothrombin was stronger in astrocytes and the vessel walls in SNpc of PD brains. PAR-1 was expressed in human astrocytes and neurons, but not in oligodendrocytes or microglia as determined by RT-PCR. We investigated thrombin-mediated activation of human astrocytes. Thrombin treatment activates human astrocytes and induces morphologic change and a marked increase in proliferation of astrocytes. Increased expression of glial cell line-derived growth factor and glutathione peroxidase (GPx) but no change in the expression of nerve growth factor and inflammatory cytokines/chemokine (IL-lp, IL-6, IL-8, MCP-1) was found in thrombin/PAR-activated astrocytes. Next, we studied the neuroprotective effect exerted by thrombin-activated astrocytes in human cerebral neuron X human neuroblastoma hybrid neurons. Although thrombin showed neurotoxicity against human hybrid neurons in a dose-dependent manner, the conditioned media derived from thrombin-pretreated astrocyte cultures promoted the survival of human hybrid neurons. The protective effect was completely inhibited with a GPx inhibitor, mercaptosuccinic acid, indicating that GPx released from thrombin/PAR-activated astrocytes is responsible for neuroprotection of hybrid neurons against thrombin cytotoxicity. The present study suggests that the increased expression of PAR-1 in astrocytes in SNpc of PD brain is the restorative move taken by the brain to provide neuroprotection against neuronal degeneration and cell death of dopaminergic neurons caused by noxious insults during the progression of PD pathology.
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Kim</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Brain Disease Research Center, Ajou University School of Medicine</s1><s2>Suwon</s2><s3>KOR</s3><sZ>4 aut.</sZ></inist:fA14><country>Corée du Sud</country><wicri:noRegion>Suwon</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Division of Neurology, Department of Medicine, University of British Columbia</s1><s2>Vancouver</s2><s3>CAN</s3><sZ>4 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">06-0096785</idno><date when="2006">2006</date><idno type="stanalyst">PASCAL 06-0096785 INIST</idno><idno type="RBID">Pascal:06-0096785</idno><idno type="wicri:Area/PascalFrancis/Corpus">000864</idno><idno type="wicri:Area/PascalFrancis/Curation">000459</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000681</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000681</idno><idno type="wicri:doubleKey">0022-3069:2006:Ishida Y:upregulation:of:protease</idno><idno type="wicri:Area/Main/Merge">002B79</idno><idno type="wicri:Area/Main/Curation">002892</idno><idno type="wicri:Area/Main/Exploration">002892</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Upregulation of protease-activated receptor-1 in astrocytes in parkinson disease : Astrocyte-mediated neuroprotection through increased levels of glutathione peroxidase</title><author><name sortKey="Ishida, Yuri" sort="Ishida, Yuri" uniqKey="Ishida Y" first="Yuri" last="Ishida">Yuri Ishida</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Neurology, Shimane University School of Medicine</s1><s2>Izumo</s2><s3>JPN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ></inist:fA14><country>Japon</country><wicri:noRegion>Izumo</wicri:noRegion></affiliation></author><author><name sortKey="Nagai, Atsushi" sort="Nagai, Atsushi" uniqKey="Nagai A" first="Atsushi" last="Nagai">Atsushi Nagai</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Laboratory Medicine, Shimane University School of Medicine</s1><s2>Izumo</s2><s3>JPN</s3><sZ>2 aut.</sZ></inist:fA14><country>Japon</country><wicri:noRegion>Izumo</wicri:noRegion></affiliation></author><author><name sortKey="Kobayashi, Shotai" sort="Kobayashi, Shotai" uniqKey="Kobayashi S" first="Shotai" last="Kobayashi">Shotai Kobayashi</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Neurology, Shimane University School of Medicine</s1><s2>Izumo</s2><s3>JPN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ></inist:fA14><country>Japon</country><wicri:noRegion>Izumo</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Seung U" sort="Kim, Seung U" uniqKey="Kim S" first="Seung U." last="Kim">Seung U. Kim</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Brain Disease Research Center, Ajou University School of Medicine</s1><s2>Suwon</s2><s3>KOR</s3><sZ>4 aut.</sZ></inist:fA14><country>Corée du Sud</country><wicri:noRegion>Suwon</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Division of Neurology, Department of Medicine, University of British Columbia</s1><s2>Vancouver</s2><s3>CAN</s3><sZ>4 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Journal of neuropathology and experimental neurology</title><title level="j" type="abbreviated">J. neuropathol. exp. neurol.</title><idno type="ISSN">0022-3069</idno><imprint><date when="2006">2006</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of neuropathology and experimental neurology</title><title level="j" type="abbreviated">J. neuropathol. exp. neurol.</title><idno type="ISSN">0022-3069</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Astrocyte</term><term>Biological receptor</term><term>Cell line</term><term>Cell proliferation</term><term>Glial cell</term><term>Glial cell line derived neurotrophic factor</term><term>Glutathione peroxidase</term><term>Growth factor</term><term>Nervous system diseases</term><term>Parkinson disease</term><term>Peptidases</term><term>Thrombin</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Système nerveux pathologie</term><term>Parkinson maladie</term><term>Peptidases</term><term>Récepteur biologique</term><term>Astrocyte</term><term>Glutathione peroxidase</term><term>Cellule gliale</term><term>Multiplication cellulaire</term><term>Lignée cellulaire</term><term>Facteur croissance</term><term>Facteur GDNF</term><term>Thrombin</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In the present study, we investigated the expression of protease-activated receptors (PARs), receptors for thrombin, in substantia nigra pars compacta (SNpc) of Parkinson disease (PD) brains and cultures of human neurons, astrocytes, oligodendrocytes, and microglia as determined by immunocytochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). Expression of PAR-1 was demonstrated only in glial fibrillary acidic protein-positive astrocytes in SNpc, and the number of astrocytes expressing PAR-1 increased in SNpc of PD as compared with nonneurologic control brain. Immunoreactivity for thrombin and prothrombin was stronger in astrocytes and the vessel walls in SNpc of PD brains. PAR-1 was expressed in human astrocytes and neurons, but not in oligodendrocytes or microglia as determined by RT-PCR. We investigated thrombin-mediated activation of human astrocytes. Thrombin treatment activates human astrocytes and induces morphologic change and a marked increase in proliferation of astrocytes. Increased expression of glial cell line-derived growth factor and glutathione peroxidase (GPx) but no change in the expression of nerve growth factor and inflammatory cytokines/chemokine (IL-lp, IL-6, IL-8, MCP-1) was found in thrombin/PAR-activated astrocytes. Next, we studied the neuroprotective effect exerted by thrombin-activated astrocytes in human cerebral neuron X human neuroblastoma hybrid neurons. Although thrombin showed neurotoxicity against human hybrid neurons in a dose-dependent manner, the conditioned media derived from thrombin-pretreated astrocyte cultures promoted the survival of human hybrid neurons. The protective effect was completely inhibited with a GPx inhibitor, mercaptosuccinic acid, indicating that GPx released from thrombin/PAR-activated astrocytes is responsible for neuroprotection of hybrid neurons against thrombin cytotoxicity. The present study suggests that the increased expression of PAR-1 in astrocytes in SNpc of PD brain is the restorative move taken by the brain to provide neuroprotection against neuronal degeneration and cell death of dopaminergic neurons caused by noxious insults during the progression of PD pathology.</div></front></TEI><affiliations><list><country><li>Canada</li><li>Corée du Sud</li><li>Japon</li></country></list><tree><country name="Japon"><noRegion><name sortKey="Ishida, Yuri" sort="Ishida, Yuri" uniqKey="Ishida Y" first="Yuri" last="Ishida">Yuri Ishida</name></noRegion><name sortKey="Kobayashi, Shotai" sort="Kobayashi, Shotai" uniqKey="Kobayashi S" first="Shotai" last="Kobayashi">Shotai Kobayashi</name><name sortKey="Nagai, Atsushi" sort="Nagai, Atsushi" uniqKey="Nagai A" first="Atsushi" last="Nagai">Atsushi Nagai</name></country><country name="Corée du Sud"><noRegion><name sortKey="Kim, Seung U" sort="Kim, Seung U" uniqKey="Kim S" first="Seung U." last="Kim">Seung U. Kim</name></noRegion></country><country name="Canada"><noRegion><name sortKey="Kim, Seung U" sort="Kim, Seung U" uniqKey="Kim S" first="Seung U." last="Kim">Seung U. Kim</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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