Expression of the proto-oncogene Ret, a component of the GDNF receptor complex, persists in human substantia nigra neurons in Parkinson's disease
Identifieur interne : 003878 ( Main/Exploration ); précédent : 003877; suivant : 003879Expression of the proto-oncogene Ret, a component of the GDNF receptor complex, persists in human substantia nigra neurons in Parkinson's disease
Auteurs : Douglas G. Walker [Canada] ; Thomas G. Beach [Canada, États-Unis] ; Ren Xu [États-Unis] ; Jack Lile [États-Unis] ; Klaus D. Beck [États-Unis] ; Edith G. Mcgeer [Canada] ; Patrick L. Mcgeer [Canada]Source :
- [ 0006-8993 ]
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
- Adult, Aged, Aged, 80 and over, Animals, Biological receptor, Cell Line, Dopamine (physiology), Drosophila Proteins, Female, Gene Expression (physiology), Gene expression, Glial Cell Line-Derived Neurotrophic Factor Receptors, Glial cell line derived neurotrophic factor, Growth factor, Human, Humans, Immunoblotting, Immunohistochemistry, Locus niger, Male, Middle Aged, Monocytes, Neurons (chemistry), Parkinson Disease (metabolism), Parkinson disease, Protein-Tyrosine Kinases (analysis), Proto-Oncogene Proteins (analysis), Proto-Oncogene Proteins (genetics), Proto-Oncogene Proteins c-ret, RNA, Messenger (analysis), Rats, Rats, Sprague-Dawley, Receptor Protein-Tyrosine Kinases (analysis), Receptor Protein-Tyrosine Kinases (genetics), Substantia Nigra (chemistry), Substantia Nigra (cytology), Substantia Nigra (enzymology).
- MESH :
- chemical , analysis : Protein-Tyrosine Kinases, Proto-Oncogene Proteins, RNA, Messenger, Receptor Protein-Tyrosine Kinases.
- chemical , genetics : Proto-Oncogene Proteins, Receptor Protein-Tyrosine Kinases.
- chemical , physiology : Dopamine.
- chemistry : Neurons, Substantia Nigra.
- cytology : Substantia Nigra.
- enzymology : Substantia Nigra.
- metabolism : Parkinson Disease.
- physiology : Gene Expression.
- Adult, Aged, Aged, 80 and over, Animals, Cell Line, Drosophila Proteins, Female, Glial Cell Line-Derived Neurotrophic Factor Receptors, Humans, Immunoblotting, Immunohistochemistry, Male, Middle Aged, Monocytes, Proto-Oncogene Proteins c-ret, Rats, Rats, Sprague-Dawley.
Abstract
The proto-oncogene Ret, a membrane-associated receptor protein tyrosine kinase, has recently been shown to be a component of the glial cell line-derived neurotrophic factor (GDNF) receptor complex. GDNF has potent dopaminergic neurotrophic properties and has been suggested as a treatment for Parkinson's disease (PD). In this study, tissue sections of human substantia nigra (SN) from normal and PD cases were examined to determine the pattern of Ret expression in this region, and whether there was continued Ret expression in surviving dopaminergic neurons in PD cases. Using a polyclonal antibody to the amino terminal of Ret, immunoreactivity was localized in the SN to dopaminergic neurons. The antibody predominantly identified punctate deposits within cells. A similar pattern of immunoreactivity was observed in rat and monkey SN neurons. In neurologically normal cases, immunoreactivity was detected in many of the SN neurons. In all the PD cases studied, continued expression of Ret was observed in many of the surviving dopaminergic neurons. In certain cases, it was also detected on cells with the morphology of microglia. Ret expression by microglia was confirmed by immunoblot analysis on the human THP-1 macrophage type cell line. However, these cells did not express the mRNA for GDNFRα, the other component of the GDNF receptor complex.
Url:
DOI: 10.1016/S0006-8993(98)00131-0
Affiliations:
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Le document en format XML
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Walker</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Kinsmen Laboratory of Neurological Research and Neurodegenerative Disease Centre, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Canada</country><wicri:regionArea>Corresponding author. Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Beach, Thomas G" sort="Beach, Thomas G" uniqKey="Beach T" first="Thomas G." last="Beach">Thomas G. Beach</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Pathology, Faculty of Medicine, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation><affiliation wicri:level="2"><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>1Present address: Sun Health Research Institute, P.O. Box 1278, Sun City, AZ 85380</wicri:regionArea><placeName><region type="state">Arizona</region></placeName></affiliation></author><author><name sortKey="Xu, Ren" sort="Xu, Ren" uniqKey="Xu R" first="Ren" last="Xu">Ren Xu</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Amgen, Thousand Oaks, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Lile, Jack" sort="Lile, Jack" uniqKey="Lile J" first="Jack" last="Lile">Jack Lile</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Amgen, Thousand Oaks, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Beck, Klaus D" sort="Beck, Klaus D" uniqKey="Beck K" first="Klaus D." last="Beck">Klaus D. Beck</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Amgen, Thousand Oaks, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Mcgeer, Edith G" sort="Mcgeer, Edith G" uniqKey="Mcgeer E" first="Edith G." last="Mcgeer">Edith G. Mcgeer</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Kinsmen Laboratory of Neurological Research and Neurodegenerative Disease Centre, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="L Mcgeer, Patrick" sort="L Mcgeer, Patrick" uniqKey="L Mcgeer P" first="Patrick" last="L. Mcgeer">Patrick L. Mcgeer</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Kinsmen Laboratory of Neurological Research and Neurodegenerative Disease Centre, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author></analytic><series><idno type="ISSN">0006-8993</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0006-8993</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Animals</term><term>Biological receptor</term><term>Cell Line</term><term>Dopamine (physiology)</term><term>Drosophila Proteins</term><term>Female</term><term>Gene Expression (physiology)</term><term>Gene expression</term><term>Glial Cell Line-Derived Neurotrophic Factor Receptors</term><term>Glial cell line derived neurotrophic factor</term><term>Growth factor</term><term>Human</term><term>Humans</term><term>Immunoblotting</term><term>Immunohistochemistry</term><term>Locus niger</term><term>Male</term><term>Middle Aged</term><term>Monocytes</term><term>Neurons (chemistry)</term><term>Parkinson Disease (metabolism)</term><term>Parkinson disease</term><term>Protein-Tyrosine Kinases (analysis)</term><term>Proto-Oncogene Proteins (analysis)</term><term>Proto-Oncogene Proteins (genetics)</term><term>Proto-Oncogene Proteins c-ret</term><term>RNA, Messenger (analysis)</term><term>Rats</term><term>Rats, Sprague-Dawley</term><term>Receptor Protein-Tyrosine Kinases (analysis)</term><term>Receptor Protein-Tyrosine Kinases (genetics)</term><term>Substantia Nigra (chemistry)</term><term>Substantia Nigra (cytology)</term><term>Substantia Nigra (enzymology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Protein-Tyrosine Kinases</term><term>Proto-Oncogene Proteins</term><term>RNA, Messenger</term><term>Receptor Protein-Tyrosine Kinases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Proto-Oncogene Proteins</term><term>Receptor Protein-Tyrosine Kinases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Dopamine</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Neurons</term><term>Substantia Nigra</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Substantia Nigra</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Substantia Nigra</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Gene Expression</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Animals</term><term>Cell Line</term><term>Drosophila Proteins</term><term>Female</term><term>Glial Cell Line-Derived Neurotrophic Factor Receptors</term><term>Humans</term><term>Immunoblotting</term><term>Immunohistochemistry</term><term>Male</term><term>Middle Aged</term><term>Monocytes</term><term>Proto-Oncogene Proteins c-ret</term><term>Rats</term><term>Rats, Sprague-Dawley</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Expression génique</term><term>Facteur GDNF</term><term>Facteur croissance</term><term>Gène Ret</term><term>Homme</term><term>Locus niger</term><term>Parkinson maladie</term><term>Récepteur biologique</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The proto-oncogene Ret, a membrane-associated receptor protein tyrosine kinase, has recently been shown to be a component of the glial cell line-derived neurotrophic factor (GDNF) receptor complex. GDNF has potent dopaminergic neurotrophic properties and has been suggested as a treatment for Parkinson's disease (PD). In this study, tissue sections of human substantia nigra (SN) from normal and PD cases were examined to determine the pattern of Ret expression in this region, and whether there was continued Ret expression in surviving dopaminergic neurons in PD cases. Using a polyclonal antibody to the amino terminal of Ret, immunoreactivity was localized in the SN to dopaminergic neurons. The antibody predominantly identified punctate deposits within cells. A similar pattern of immunoreactivity was observed in rat and monkey SN neurons. In neurologically normal cases, immunoreactivity was detected in many of the SN neurons. In all the PD cases studied, continued expression of Ret was observed in many of the surviving dopaminergic neurons. In certain cases, it was also detected on cells with the morphology of microglia. Ret expression by microglia was confirmed by immunoblot analysis on the human THP-1 macrophage type cell line. However, these cells did not express the mRNA for GDNFRα, the other component of the GDNF receptor complex.</div></front></TEI><affiliations><list><country><li>Canada</li><li>États-Unis</li></country><region><li>Arizona</li><li>Californie</li></region></list><tree><country name="Canada"><noRegion><name sortKey="Walker, Douglas G" sort="Walker, Douglas G" uniqKey="Walker D" first="Douglas G." last="Walker">Douglas G. Walker</name></noRegion><name sortKey="Beach, Thomas G" sort="Beach, Thomas G" uniqKey="Beach T" first="Thomas G." last="Beach">Thomas G. Beach</name><name sortKey="L Mcgeer, Patrick" sort="L Mcgeer, Patrick" uniqKey="L Mcgeer P" first="Patrick" last="L. Mcgeer">Patrick L. Mcgeer</name><name sortKey="Mcgeer, Edith G" sort="Mcgeer, Edith G" uniqKey="Mcgeer E" first="Edith G." last="Mcgeer">Edith G. Mcgeer</name><name sortKey="Walker, Douglas G" sort="Walker, Douglas G" uniqKey="Walker D" first="Douglas G." last="Walker">Douglas G. Walker</name></country><country name="États-Unis"><region name="Arizona"><name sortKey="Beach, Thomas G" sort="Beach, Thomas G" uniqKey="Beach T" first="Thomas G." last="Beach">Thomas G. Beach</name></region><name sortKey="Beck, Klaus D" sort="Beck, Klaus D" uniqKey="Beck K" first="Klaus D." last="Beck">Klaus D. Beck</name><name sortKey="Lile, Jack" sort="Lile, Jack" uniqKey="Lile J" first="Jack" last="Lile">Jack Lile</name><name sortKey="Xu, Ren" sort="Xu, Ren" uniqKey="Xu R" first="Ren" last="Xu">Ren Xu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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