Caspase-3: A vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson's disease
Identifieur interne : 003886 ( Main/Exploration ); précédent : 003885; suivant : 003887Caspase-3: A vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson's disease
Auteurs : Andreas Hartmann [France] ; Stéphane Hunot [France] ; Patrick P. Michel [France] ; Marie-Paule Muriel [France] ; Sheela Vyas [Royaume-Uni] ; Baptiste A. Faucheux [France] ; Annick Mouatt-Prigent [France] ; Hélène Turmel [France] ; Anu Srinivasan [États-Unis] ; Merle Ruberg [France] ; Gerard I. Evan [Royaume-Uni] ; Yves Agid [France] ; Etienne C. Hirsch [France]Source :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2000.
English descriptors
- KwdEn :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (pharmacology), Aged, Aged, 80 and over, Animals, Apoptosis, Blotting, Western, Brain (enzymology), Brain (ultrastructure), Caspase 3, Caspases (biosynthesis), Caspases (physiology), Cells, Cultured, Dopamine (metabolism), Dopamine Agents (pharmacology), Enzyme Activation, Humans, Immunohistochemistry, Male, Mesencephalon (enzymology), Mice, Mice, Inbred C57BL, Neurons (enzymology), Neurons (ultrastructure), Parkinson Disease (enzymology), Parkinson Disease (metabolism), Rats, Substantia Nigra (enzymology), Tissue Distribution, Ventral Tegmental Area (enzymology).
- MESH :
- chemical , biosynthesis : Caspases.
- chemical , metabolism : Dopamine.
- chemical , pharmacology : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Dopamine Agents.
- enzymology : Brain, Mesencephalon, Neurons, Parkinson Disease, Substantia Nigra, Ventral Tegmental Area.
- metabolism : Parkinson Disease.
- chemical , physiology : Caspases.
- ultrastructure : Brain, Neurons.
- Aged, Aged, 80 and over, Animals, Apoptosis, Blotting, Western, Caspase 3, Cells, Cultured, Enzyme Activation, Humans, Immunohistochemistry, Male, Mice, Mice, Inbred C57BL, Rats, Tissue Distribution.
Abstract
Caspase-3 is an effector of apoptosis in experimental
models of Parkinson's disease (PD). However, its potential role in the
human pathology remains to be demonstrated. Using caspase-3
immunohistochemistry on the postmortem human brain, we observed a
positive correlation between the degree of neuronal loss in
dopaminergic (DA) cell groups affected in the mesencephalon of PD
patients and the percentage of caspase-3-positive neurons in these cell
groups in control subjects and a significant decrease of
caspase-3-positive pigmented neurons in the substantia nigra pars
compacta of PD patients compared with controls that also could be
observed in an animal model of PD. This suggests that neurons
expressing caspase-3 are more sensitive to the pathological process
than those that do not express the protein. In addition, using an
antibody raised against activated caspase-3, the percentage of active
caspase-3-positive neurons among DA neurons was significantly higher in
PD patients than in controls. Finally, electron microscopy analysis in
the human brain and
Url:
PubMed: 10688892
PubMed Central: 16023
Affiliations:
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Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Caspase-3: A vulnerability factor and final effector in
apoptotic death of dopaminergic neurons in
Parkinson's disease</title>
<author><name sortKey="Hartmann, Andreas" sort="Hartmann, Andreas" uniqKey="Hartmann A" first="Andreas" last="Hartmann">Andreas Hartmann</name>
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<author><name sortKey="Hunot, Stephane" sort="Hunot, Stephane" uniqKey="Hunot S" first="Stéphane" last="Hunot">Stéphane Hunot</name>
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</author>
<author><name sortKey="Agid, Yves" sort="Agid, Yves" uniqKey="Agid Y" first="Yves" last="Agid">Yves Agid</name>
<affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea>
<placeName><region type="region" nuts="2">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
<placeName><settlement type="city">Paris</settlement>
<region type="region" nuts="2">Île-de-France</region>
</placeName>
<orgName type="hospital" n="4">Hôpital de la Salpêtrière</orgName>
</affiliation>
</author>
<author><name sortKey="Hirsch, Etienne C" sort="Hirsch, Etienne C" uniqKey="Hirsch E" first="Etienne C." last="Hirsch">Etienne C. Hirsch</name>
<affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea>
<placeName><region type="region" nuts="2">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title>
<idno type="ISSN">0027-8424</idno>
<idno type="eISSN">1091-6490</idno>
<imprint><date when="2000">2000</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (pharmacology)</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Animals</term>
<term>Apoptosis</term>
<term>Blotting, Western</term>
<term>Brain (enzymology)</term>
<term>Brain (ultrastructure)</term>
<term>Caspase 3</term>
<term>Caspases (biosynthesis)</term>
<term>Caspases (physiology)</term>
<term>Cells, Cultured</term>
<term>Dopamine (metabolism)</term>
<term>Dopamine Agents (pharmacology)</term>
<term>Enzyme Activation</term>
<term>Humans</term>
<term>Immunohistochemistry</term>
<term>Male</term>
<term>Mesencephalon (enzymology)</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Neurons (enzymology)</term>
<term>Neurons (ultrastructure)</term>
<term>Parkinson Disease (enzymology)</term>
<term>Parkinson Disease (metabolism)</term>
<term>Rats</term>
<term>Substantia Nigra (enzymology)</term>
<term>Tissue Distribution</term>
<term>Ventral Tegmental Area (enzymology)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Caspases</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dopamine</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term>
<term>Dopamine Agents</term>
</keywords>
<keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Brain</term>
<term>Mesencephalon</term>
<term>Neurons</term>
<term>Parkinson Disease</term>
<term>Substantia Nigra</term>
<term>Ventral Tegmental Area</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Caspases</term>
</keywords>
<keywords scheme="MESH" qualifier="ultrastructure" xml:lang="en"><term>Brain</term>
<term>Neurons</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Aged</term>
<term>Aged, 80 and over</term>
<term>Animals</term>
<term>Apoptosis</term>
<term>Blotting, Western</term>
<term>Caspase 3</term>
<term>Cells, Cultured</term>
<term>Enzyme Activation</term>
<term>Humans</term>
<term>Immunohistochemistry</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Rats</term>
<term>Tissue Distribution</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Caspase-3 is an effector of apoptosis in experimental
models of Parkinson's disease (PD). However, its potential role in the
human pathology remains to be demonstrated. Using caspase-3
immunohistochemistry on the postmortem human brain, we observed a
positive correlation between the degree of neuronal loss in
dopaminergic (DA) cell groups affected in the mesencephalon of PD
patients and the percentage of caspase-3-positive neurons in these cell
groups in control subjects and a significant decrease of
caspase-3-positive pigmented neurons in the substantia nigra pars
compacta of PD patients compared with controls that also could be
observed in an animal model of PD. This suggests that neurons
expressing caspase-3 are more sensitive to the pathological process
than those that do not express the protein. In addition, using an
antibody raised against activated caspase-3, the percentage of active
caspase-3-positive neurons among DA neurons was significantly higher in
PD patients than in controls. Finally, electron microscopy analysis in
the human brain and <italic>in vitro</italic>
data suggest that caspase-3
activation precedes and is not a consequence of apoptotic cell
death in PD.</p>
</div>
</front>
</TEI>
<affiliations><list><country><li>France</li>
<li>Royaume-Uni</li>
<li>États-Unis</li>
</country>
<region><li>Californie</li>
<li>Île-de-France</li>
</region>
<settlement><li>Paris</li>
</settlement>
<orgName><li>Hôpital de la Salpêtrière</li>
</orgName>
</list>
<tree><country name="France"><region name="Île-de-France"><name sortKey="Hartmann, Andreas" sort="Hartmann, Andreas" uniqKey="Hartmann A" first="Andreas" last="Hartmann">Andreas Hartmann</name>
</region>
<name sortKey="Agid, Yves" sort="Agid, Yves" uniqKey="Agid Y" first="Yves" last="Agid">Yves Agid</name>
<name sortKey="Faucheux, Baptiste A" sort="Faucheux, Baptiste A" uniqKey="Faucheux B" first="Baptiste A." last="Faucheux">Baptiste A. Faucheux</name>
<name sortKey="Hirsch, Etienne C" sort="Hirsch, Etienne C" uniqKey="Hirsch E" first="Etienne C." last="Hirsch">Etienne C. Hirsch</name>
<name sortKey="Hunot, Stephane" sort="Hunot, Stephane" uniqKey="Hunot S" first="Stéphane" last="Hunot">Stéphane Hunot</name>
<name sortKey="Michel, Patrick P" sort="Michel, Patrick P" uniqKey="Michel P" first="Patrick P." last="Michel">Patrick P. Michel</name>
<name sortKey="Mouatt Prigent, Annick" sort="Mouatt Prigent, Annick" uniqKey="Mouatt Prigent A" first="Annick" last="Mouatt-Prigent">Annick Mouatt-Prigent</name>
<name sortKey="Muriel, Marie Paule" sort="Muriel, Marie Paule" uniqKey="Muriel M" first="Marie-Paule" last="Muriel">Marie-Paule Muriel</name>
<name sortKey="Ruberg, Merle" sort="Ruberg, Merle" uniqKey="Ruberg M" first="Merle" last="Ruberg">Merle Ruberg</name>
<name sortKey="Turmel, Helene" sort="Turmel, Helene" uniqKey="Turmel H" first="Hélène" last="Turmel">Hélène Turmel</name>
</country>
<country name="Royaume-Uni"><noRegion><name sortKey="Vyas, Sheela" sort="Vyas, Sheela" uniqKey="Vyas S" first="Sheela" last="Vyas">Sheela Vyas</name>
</noRegion>
<name sortKey="Evan, Gerard I" sort="Evan, Gerard I" uniqKey="Evan G" first="Gerard I." last="Evan">Gerard I. Evan</name>
</country>
<country name="États-Unis"><region name="Californie"><name sortKey="Srinivasan, Anu" sort="Srinivasan, Anu" uniqKey="Srinivasan A" first="Anu" last="Srinivasan">Anu Srinivasan</name>
</region>
</country>
</tree>
</affiliations>
</record>
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