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 : 001708 ( PubMed/Checkpoint ); précédent : 001707; suivant : 001709Expression of the proto-oncogene Ret, a component of the GDNF receptor complex, persists in human substantia nigra neurons in Parkinson's disease.
Auteurs : D G Walker [Canada] ; T G Beach ; R. Xu ; J. Lile ; K D Beck ; E G Mcgeer ; P L McgeerSource :
- Brain research [ 0006-8993 ] ; 1998.
English descriptors
- KwdEn :
- Adult, Aged, Aged, 80 and over, Animals, Cell Line, Dopamine (physiology), Drosophila Proteins, Female, Gene Expression (physiology), Glial Cell Line-Derived Neurotrophic Factor Receptors, Humans, Immunoblotting, Immunohistochemistry, Male, Middle Aged, Monocytes, Neurons (chemistry), Parkinson Disease (metabolism), 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 GDNFRalpha, the other component of the GDNF receptor complex.
PubMed: 9593897
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Expression of the proto-oncogene Ret, a component of the GDNF receptor complex, persists in human substantia nigra neurons in Parkinson's disease.</title><author><name sortKey="Walker, D G" sort="Walker, D G" uniqKey="Walker D" first="D G" last="Walker">D G Walker</name><affiliation wicri:level="1"><nlm:affiliation>Kinsmen Laboratory of Neurological Research and Neurodegenerative Disease Centre, University of British Columbia, Vancouver, BC, Canada. douglas_walker@bc.sympatico.ca</nlm:affiliation><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="Beach, T G" sort="Beach, T G" uniqKey="Beach T" first="T G" last="Beach">T G Beach</name></author><author><name sortKey="Xu, R" sort="Xu, R" uniqKey="Xu R" first="R" last="Xu">R. Xu</name></author><author><name sortKey="Lile, J" sort="Lile, J" uniqKey="Lile J" first="J" last="Lile">J. Lile</name></author><author><name sortKey="Beck, K D" sort="Beck, K D" uniqKey="Beck K" first="K D" last="Beck">K D Beck</name></author><author><name sortKey="Mcgeer, E G" sort="Mcgeer, E G" uniqKey="Mcgeer E" first="E G" last="Mcgeer">E G Mcgeer</name></author><author><name sortKey="Mcgeer, P L" sort="Mcgeer, P L" uniqKey="Mcgeer P" first="P L" last="Mcgeer">P L Mcgeer</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1998">1998</date><idno type="RBID">pubmed:9593897</idno><idno type="pmid">9593897</idno><idno type="wicri:Area/PubMed/Corpus">001770</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001770</idno><idno type="wicri:Area/PubMed/Curation">001770</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001770</idno><idno type="wicri:Area/PubMed/Checkpoint">001770</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001770</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Expression of the proto-oncogene Ret, a component of the GDNF receptor complex, persists in human substantia nigra neurons in Parkinson's disease.</title><author><name sortKey="Walker, D G" sort="Walker, D G" uniqKey="Walker D" first="D G" last="Walker">D G Walker</name><affiliation wicri:level="1"><nlm:affiliation>Kinsmen Laboratory of Neurological Research and Neurodegenerative Disease Centre, University of British Columbia, Vancouver, BC, Canada. douglas_walker@bc.sympatico.ca</nlm:affiliation><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="Beach, T G" sort="Beach, T G" uniqKey="Beach T" first="T G" last="Beach">T G Beach</name></author><author><name sortKey="Xu, R" sort="Xu, R" uniqKey="Xu R" first="R" last="Xu">R. Xu</name></author><author><name sortKey="Lile, J" sort="Lile, J" uniqKey="Lile J" first="J" last="Lile">J. Lile</name></author><author><name sortKey="Beck, K D" sort="Beck, K D" uniqKey="Beck K" first="K D" last="Beck">K D Beck</name></author><author><name sortKey="Mcgeer, E G" sort="Mcgeer, E G" uniqKey="Mcgeer E" first="E G" last="Mcgeer">E G Mcgeer</name></author><author><name sortKey="Mcgeer, P L" sort="Mcgeer, P L" uniqKey="Mcgeer P" first="P L" last="Mcgeer">P L Mcgeer</name></author></analytic><series><title level="j">Brain research</title><idno type="ISSN">0006-8993</idno><imprint><date when="1998" type="published">1998</date></imprint></series></biblStruct></sourceDesc></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>Cell Line</term><term>Dopamine (physiology)</term><term>Drosophila Proteins</term><term>Female</term><term>Gene Expression (physiology)</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>Neurons (chemistry)</term><term>Parkinson Disease (metabolism)</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></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 GDNFRalpha, the other component of the GDNF receptor complex.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">9593897</PMID><DateCreated><Year>1998</Year><Month>07</Month><Day>20</Day></DateCreated><DateCompleted><Year>1998</Year><Month>07</Month><Day>20</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0006-8993</ISSN><JournalIssue CitedMedium="Print"><Volume>792</Volume><Issue>2</Issue><PubDate><Year>1998</Year><Month>May</Month><Day>11</Day></PubDate></JournalIssue><Title>Brain research</Title><ISOAbbreviation>Brain Res.</ISOAbbreviation></Journal><ArticleTitle>Expression of the proto-oncogene Ret, a component of the GDNF receptor complex, persists in human substantia nigra neurons in Parkinson's disease.</ArticleTitle><Pagination><MedlinePgn>207-17</MedlinePgn></Pagination><Abstract><AbstractText>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 GDNFRalpha, the other component of the GDNF receptor complex.</AbstractText><CopyrightInformation>Copyright 1998 Elsevier Science B.V.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Walker</LastName><ForeName>D G</ForeName><Initials>DG</Initials><AffiliationInfo><Affiliation>Kinsmen Laboratory of Neurological Research and Neurodegenerative Disease Centre, University of British Columbia, Vancouver, BC, Canada. douglas_walker@bc.sympatico.ca</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Beach</LastName><ForeName>T G</ForeName><Initials>TG</Initials></Author><Author ValidYN="Y"><LastName>Xu</LastName><ForeName>R</ForeName><Initials>R</Initials></Author><Author ValidYN="Y"><LastName>Lile</LastName><ForeName>J</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Beck</LastName><ForeName>K D</ForeName><Initials>KD</Initials></Author><Author ValidYN="Y"><LastName>McGeer</LastName><ForeName>E G</ForeName><Initials>EG</Initials></Author><Author ValidYN="Y"><LastName>McGeer</LastName><ForeName>P L</ForeName><Initials>PL</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Brain Res</MedlineTA><NlmUniqueID>0045503</NlmUniqueID><ISSNLinking>0006-8993</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D029721">Drosophila Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D051097">Glial Cell Line-Derived Neurotrophic Factor Receptors</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011518">Proto-Oncogene Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D012333">RNA, Messenger</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.10.1</RegistryNumber><NameOfSubstance UI="D011505">Protein-Tyrosine Kinases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.10.1</RegistryNumber><NameOfSubstance UI="D051096">Proto-Oncogene Proteins c-ret</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.10.1</RegistryNumber><NameOfSubstance UI="D020794">Receptor Protein-Tyrosine Kinases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.10.1</RegistryNumber><NameOfSubstance UI="C416649">Ret oncogene protein, Drosophila</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.10.1</RegistryNumber><NameOfSubstance UI="C495001">Ret protein, rat</NameOfSubstance></Chemical><Chemical><RegistryNumber>VTD58H1Z2X</RegistryNumber><NameOfSubstance UI="D004298">Dopamine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000369" MajorTopicYN="N">Aged, 80 and over</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002460" MajorTopicYN="N">Cell Line</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004298" MajorTopicYN="N">Dopamine</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D029721" MajorTopicYN="Y">Drosophila Proteins</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015870" MajorTopicYN="N">Gene Expression</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051097" MajorTopicYN="N">Glial Cell Line-Derived Neurotrophic Factor Receptors</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015151" MajorTopicYN="N">Immunoblotting</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007150" MajorTopicYN="N">Immunohistochemistry</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009000" MajorTopicYN="N">Monocytes</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009474" MajorTopicYN="N">Neurons</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010300" MajorTopicYN="N">Parkinson Disease</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011505" MajorTopicYN="N">Protein-Tyrosine Kinases</DescriptorName><QualifierName UI="Q000032" MajorTopicYN="N">analysis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011518" MajorTopicYN="N">Proto-Oncogene Proteins</DescriptorName><QualifierName UI="Q000032" MajorTopicYN="Y">analysis</QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051096" MajorTopicYN="N">Proto-Oncogene Proteins c-ret</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012333" MajorTopicYN="N">RNA, Messenger</DescriptorName><QualifierName UI="Q000032" MajorTopicYN="N">analysis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051381" MajorTopicYN="N">Rats</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017207" MajorTopicYN="N">Rats, Sprague-Dawley</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020794" MajorTopicYN="N">Receptor Protein-Tyrosine Kinases</DescriptorName><QualifierName UI="Q000032" MajorTopicYN="Y">analysis</QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013378" MajorTopicYN="N">Substantia Nigra</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName><QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName><QualifierName UI="Q000201" MajorTopicYN="N">enzymology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>1998</Year><Month>6</Month><Day>24</Day></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>1998</Year><Month>6</Month><Day>24</Day><Hour>0</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>1998</Year><Month>6</Month><Day>24</Day><Hour>0</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">9593897</ArticleId><ArticleId IdType="pii">S0006899398001310</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Canada</li></country></list><tree><noCountry><name sortKey="Beach, T G" sort="Beach, T G" uniqKey="Beach T" first="T G" last="Beach">T G Beach</name><name sortKey="Beck, K D" sort="Beck, K D" uniqKey="Beck K" first="K D" last="Beck">K D Beck</name><name sortKey="Lile, J" sort="Lile, J" uniqKey="Lile J" first="J" last="Lile">J. Lile</name><name sortKey="Mcgeer, E G" sort="Mcgeer, E G" uniqKey="Mcgeer E" first="E G" last="Mcgeer">E G Mcgeer</name><name sortKey="Mcgeer, P L" sort="Mcgeer, P L" uniqKey="Mcgeer P" first="P L" last="Mcgeer">P L Mcgeer</name><name sortKey="Xu, R" sort="Xu, R" uniqKey="Xu R" first="R" last="Xu">R. Xu</name></noCountry><country name="Canada"><noRegion><name sortKey="Walker, D G" sort="Walker, D G" uniqKey="Walker D" first="D G" last="Walker">D G Walker</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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