Pro‐apoptotic protein glyceraldehyde‐3‐phosphate dehydrogenase promotes the formation of Lewy body‐like inclusions
Identifieur interne : 002680 ( Main/Corpus ); précédent : 002679; suivant : 002681Pro‐apoptotic protein glyceraldehyde‐3‐phosphate dehydrogenase promotes the formation of Lewy body‐like inclusions
Auteurs : Katsumi Tsuchiya ; Hisao Tajima ; Toyoyasu Kuwae ; Takao Takeshima ; Toshiya Nakano ; Masaharu Tanaka ; Katsuyoshi Sunaga ; Yoko Fukuhara ; Kenji Nakashima ; Eisaku Ohama ; Hideki Mochizuki ; Yoshikuni Mizuno ; Nobuo Katsube ; Ryoichi IshitaniSource :
- European Journal of Neuroscience [ 0953-816X ] ; 2005-01.
English descriptors
Abstract
Glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) has long been recognized as a classical glycolytic protein; however, previous studies by our group and others have demonstrated that GAPDH is a general mediator initiating one or more apoptotic cascades. Our most recent findings have elucidated that an expression of a pro‐apoptotic protein GAPDH is critically regulated at the promoter region of the gene. Apoptotic signals for its subsequent aggregate formation and nuclear translocation are controlled by the respective functional domains harboured within its cDNA component. In this study, coexpression of GAPDH with either wild‐type or mutant (A53T) α‐synuclein and less likely with β‐synuclein in transfected COS‐7 cells was found to induce Lewy body‐like cytoplasmic inclusions. Unlike its full‐length construct, the deleted mutant GAPDH construct (C66) abolished these apoptotic signals, disfavouring the formation of inclusions. The generated inclusions were ubiquitin‐ and thioflavin S‐positive appearing fibrils. Furthermore, GAPDH coimmunoprecipitated with wild‐type α‐synuclein in this paradigm. Importantly, immunohistochemical examinations of post mortem materials from patients with sporadic Parkinson's disease revealed the colocalized profiles immunoreactive against these two proteins in the peripheral zone of Lewy bodies from the affected brain regions (i.e. locus coeruleus). Moreover, a quantitative assessment showed that about 20% of Lewy bodies displayed both antigenicities. These results suggest that pro‐apoptotic protein GAPDH may be involved in the Lewy body formation in vivo, probably associated with the apoptotic death pathway.
Url:
DOI: 10.1111/j.1460-9568.2005.03870.x
Links to Exploration step
ISTEX:0B7F2222CCCA27AAE1C98A644EB99EF5D6A3103DLe document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Pro‐apoptotic protein glyceraldehyde‐3‐phosphate dehydrogenase promotes the formation of Lewy body‐like inclusions</title><author><name sortKey="Tsuchiya, Katsumi" sort="Tsuchiya, Katsumi" uniqKey="Tsuchiya K" first="Katsumi" last="Tsuchiya">Katsumi Tsuchiya</name><affiliation><mods:affiliation>Group on Cellular Neurobiology, Josai University, Sakado, Saitama 350–0248, Japan</mods:affiliation></affiliation></author><author><name sortKey="Tajima, Hisao" sort="Tajima, Hisao" uniqKey="Tajima H" first="Hisao" last="Tajima">Hisao Tajima</name><affiliation><mods:affiliation>Minase Research Institute, Ono Pharmaceutical Co., Ltd, Osaka 618–8585, Japan</mods:affiliation></affiliation></author><author><name sortKey="Kuwae, Toyoyasu" sort="Kuwae, Toyoyasu" uniqKey="Kuwae T" first="Toyoyasu" last="Kuwae">Toyoyasu Kuwae</name><affiliation><mods:affiliation>Group on Cellular Neurobiology, Josai University, Sakado, Saitama 350–0248, Japan</mods:affiliation></affiliation></author><author><name sortKey="Takeshima, Takao" sort="Takeshima, Takao" uniqKey="Takeshima T" first="Takao" last="Takeshima">Takao Takeshima</name><affiliation><mods:affiliation>Department of Neurology and Neuropathology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683–8504, Japan</mods:affiliation></affiliation></author><author><name sortKey="Nakano, Toshiya" sort="Nakano, Toshiya" uniqKey="Nakano T" first="Toshiya" last="Nakano">Toshiya Nakano</name><affiliation><mods:affiliation>Department of Neurology and Neuropathology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683–8504, Japan</mods:affiliation></affiliation></author><author><name sortKey="Tanaka, Masaharu" sort="Tanaka, Masaharu" uniqKey="Tanaka M" first="Masaharu" last="Tanaka">Masaharu Tanaka</name><affiliation><mods:affiliation>Minase Research Institute, Ono Pharmaceutical Co., Ltd, Osaka 618–8585, Japan</mods:affiliation></affiliation></author><author><name sortKey="Sunaga, Katsuyoshi" sort="Sunaga, Katsuyoshi" uniqKey="Sunaga K" first="Katsuyoshi" last="Sunaga">Katsuyoshi Sunaga</name><affiliation><mods:affiliation>Group on Cellular Neurobiology, Josai University, Sakado, Saitama 350–0248, Japan</mods:affiliation></affiliation></author><author><name sortKey="Fukuhara, Yoko" sort="Fukuhara, Yoko" uniqKey="Fukuhara Y" first="Yoko" last="Fukuhara">Yoko Fukuhara</name><affiliation><mods:affiliation>Department of Neurology and Neuropathology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683–8504, Japan</mods:affiliation></affiliation></author><author><name sortKey="Nakashima, Kenji" sort="Nakashima, Kenji" uniqKey="Nakashima K" first="Kenji" last="Nakashima">Kenji Nakashima</name><affiliation><mods:affiliation>Department of Neurology and Neuropathology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683–8504, Japan</mods:affiliation></affiliation></author><author><name sortKey="Ohama, Eisaku" sort="Ohama, Eisaku" uniqKey="Ohama E" first="Eisaku" last="Ohama">Eisaku Ohama</name><affiliation><mods:affiliation>Department of Neurology and Neuropathology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683–8504, Japan</mods:affiliation></affiliation></author><author><name sortKey="Mochizuki, Hideki" sort="Mochizuki, Hideki" uniqKey="Mochizuki H" first="Hideki" last="Mochizuki">Hideki Mochizuki</name><affiliation><mods:affiliation>Department of Neurology, Juntendo University School of Medicine, Tokyo 113–8421, Japan</mods:affiliation></affiliation></author><author><name sortKey="Mizuno, Yoshikuni" sort="Mizuno, Yoshikuni" uniqKey="Mizuno Y" first="Yoshikuni" last="Mizuno">Yoshikuni Mizuno</name><affiliation><mods:affiliation>Department of Neurology, Juntendo University School of Medicine, Tokyo 113–8421, Japan</mods:affiliation></affiliation></author><author><name sortKey="Katsube, Nobuo" sort="Katsube, Nobuo" uniqKey="Katsube N" first="Nobuo" last="Katsube">Nobuo Katsube</name><affiliation><mods:affiliation>Minase Research Institute, Ono Pharmaceutical Co., Ltd, Osaka 618–8585, Japan</mods:affiliation></affiliation></author><author><name sortKey="Ishitani, Ryoichi" sort="Ishitani, Ryoichi" uniqKey="Ishitani R" first="Ryoichi" last="Ishitani">Ryoichi Ishitani</name><affiliation><mods:affiliation>Group on Cellular Neurobiology, Josai University, Sakado, Saitama 350–0248, Japan</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:0B7F2222CCCA27AAE1C98A644EB99EF5D6A3103D</idno><date when="2005" year="2005">2005</date><idno type="doi">10.1111/j.1460-9568.2005.03870.x</idno><idno type="url">https://api.istex.fr/document/0B7F2222CCCA27AAE1C98A644EB99EF5D6A3103D/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">002680</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Pro‐apoptotic protein glyceraldehyde‐3‐phosphate dehydrogenase promotes the formation of Lewy body‐like inclusions</title><author><name sortKey="Tsuchiya, Katsumi" sort="Tsuchiya, Katsumi" uniqKey="Tsuchiya K" first="Katsumi" last="Tsuchiya">Katsumi Tsuchiya</name><affiliation><mods:affiliation>Group on Cellular Neurobiology, Josai University, Sakado, Saitama 350–0248, Japan</mods:affiliation></affiliation></author><author><name sortKey="Tajima, Hisao" sort="Tajima, Hisao" uniqKey="Tajima H" first="Hisao" last="Tajima">Hisao Tajima</name><affiliation><mods:affiliation>Minase Research Institute, Ono Pharmaceutical Co., Ltd, Osaka 618–8585, Japan</mods:affiliation></affiliation></author><author><name sortKey="Kuwae, Toyoyasu" sort="Kuwae, Toyoyasu" uniqKey="Kuwae T" first="Toyoyasu" last="Kuwae">Toyoyasu Kuwae</name><affiliation><mods:affiliation>Group on Cellular Neurobiology, Josai University, Sakado, Saitama 350–0248, Japan</mods:affiliation></affiliation></author><author><name sortKey="Takeshima, Takao" sort="Takeshima, Takao" uniqKey="Takeshima T" first="Takao" last="Takeshima">Takao Takeshima</name><affiliation><mods:affiliation>Department of Neurology and Neuropathology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683–8504, Japan</mods:affiliation></affiliation></author><author><name sortKey="Nakano, Toshiya" sort="Nakano, Toshiya" uniqKey="Nakano T" first="Toshiya" last="Nakano">Toshiya Nakano</name><affiliation><mods:affiliation>Department of Neurology and Neuropathology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683–8504, Japan</mods:affiliation></affiliation></author><author><name sortKey="Tanaka, Masaharu" sort="Tanaka, Masaharu" uniqKey="Tanaka M" first="Masaharu" last="Tanaka">Masaharu Tanaka</name><affiliation><mods:affiliation>Minase Research Institute, Ono Pharmaceutical Co., Ltd, Osaka 618–8585, Japan</mods:affiliation></affiliation></author><author><name sortKey="Sunaga, Katsuyoshi" sort="Sunaga, Katsuyoshi" uniqKey="Sunaga K" first="Katsuyoshi" last="Sunaga">Katsuyoshi Sunaga</name><affiliation><mods:affiliation>Group on Cellular Neurobiology, Josai University, Sakado, Saitama 350–0248, Japan</mods:affiliation></affiliation></author><author><name sortKey="Fukuhara, Yoko" sort="Fukuhara, Yoko" uniqKey="Fukuhara Y" first="Yoko" last="Fukuhara">Yoko Fukuhara</name><affiliation><mods:affiliation>Department of Neurology and Neuropathology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683–8504, Japan</mods:affiliation></affiliation></author><author><name sortKey="Nakashima, Kenji" sort="Nakashima, Kenji" uniqKey="Nakashima K" first="Kenji" last="Nakashima">Kenji Nakashima</name><affiliation><mods:affiliation>Department of Neurology and Neuropathology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683–8504, Japan</mods:affiliation></affiliation></author><author><name sortKey="Ohama, Eisaku" sort="Ohama, Eisaku" uniqKey="Ohama E" first="Eisaku" last="Ohama">Eisaku Ohama</name><affiliation><mods:affiliation>Department of Neurology and Neuropathology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683–8504, Japan</mods:affiliation></affiliation></author><author><name sortKey="Mochizuki, Hideki" sort="Mochizuki, Hideki" uniqKey="Mochizuki H" first="Hideki" last="Mochizuki">Hideki Mochizuki</name><affiliation><mods:affiliation>Department of Neurology, Juntendo University School of Medicine, Tokyo 113–8421, Japan</mods:affiliation></affiliation></author><author><name sortKey="Mizuno, Yoshikuni" sort="Mizuno, Yoshikuni" uniqKey="Mizuno Y" first="Yoshikuni" last="Mizuno">Yoshikuni Mizuno</name><affiliation><mods:affiliation>Department of Neurology, Juntendo University School of Medicine, Tokyo 113–8421, Japan</mods:affiliation></affiliation></author><author><name sortKey="Katsube, Nobuo" sort="Katsube, Nobuo" uniqKey="Katsube N" first="Nobuo" last="Katsube">Nobuo Katsube</name><affiliation><mods:affiliation>Minase Research Institute, Ono Pharmaceutical Co., Ltd, Osaka 618–8585, Japan</mods:affiliation></affiliation></author><author><name sortKey="Ishitani, Ryoichi" sort="Ishitani, Ryoichi" uniqKey="Ishitani R" first="Ryoichi" last="Ishitani">Ryoichi Ishitani</name><affiliation><mods:affiliation>Group on Cellular Neurobiology, Josai University, Sakado, Saitama 350–0248, Japan</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">European Journal of Neuroscience</title><idno type="ISSN">0953-816X</idno><idno type="eISSN">1460-9568</idno><imprint><publisher>Blackwell Science Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2005-01">2005-01</date><biblScope unit="volume">21</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="317">317</biblScope><biblScope unit="page" to="326">326</biblScope></imprint><idno type="ISSN">0953-816X</idno></series><idno type="istex">0B7F2222CCCA27AAE1C98A644EB99EF5D6A3103D</idno><idno type="DOI">10.1111/j.1460-9568.2005.03870.x</idno><idno type="ArticleID">EJN3870</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0953-816X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Lewy bodies</term><term>Parkinson's disease</term><term>coaggregation</term><term>pro‐apoptotic GAPDH</term><term>wild‐type α‐synuclein</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) has long been recognized as a classical glycolytic protein; however, previous studies by our group and others have demonstrated that GAPDH is a general mediator initiating one or more apoptotic cascades. Our most recent findings have elucidated that an expression of a pro‐apoptotic protein GAPDH is critically regulated at the promoter region of the gene. Apoptotic signals for its subsequent aggregate formation and nuclear translocation are controlled by the respective functional domains harboured within its cDNA component. In this study, coexpression of GAPDH with either wild‐type or mutant (A53T) α‐synuclein and less likely with β‐synuclein in transfected COS‐7 cells was found to induce Lewy body‐like cytoplasmic inclusions. Unlike its full‐length construct, the deleted mutant GAPDH construct (C66) abolished these apoptotic signals, disfavouring the formation of inclusions. The generated inclusions were ubiquitin‐ and thioflavin S‐positive appearing fibrils. Furthermore, GAPDH coimmunoprecipitated with wild‐type α‐synuclein in this paradigm. Importantly, immunohistochemical examinations of post mortem materials from patients with sporadic Parkinson's disease revealed the colocalized profiles immunoreactive against these two proteins in the peripheral zone of Lewy bodies from the affected brain regions (i.e. locus coeruleus). Moreover, a quantitative assessment showed that about 20% of Lewy bodies displayed both antigenicities. These results suggest that pro‐apoptotic protein GAPDH may be involved in the Lewy body formation in vivo, probably associated with the apoptotic death pathway.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Katsumi Tsuchiya</name><affiliations><json:string>Group on Cellular Neurobiology, Josai University, Sakado, Saitama 350–0248, Japan</json:string></affiliations></json:item><json:item><name>Hisao Tajima</name><affiliations><json:string>Minase Research Institute, Ono Pharmaceutical Co., Ltd, Osaka 618–8585, Japan</json:string></affiliations></json:item><json:item><name>Toyoyasu Kuwae</name><affiliations><json:string>Group on Cellular Neurobiology, Josai University, Sakado, Saitama 350–0248, Japan</json:string></affiliations></json:item><json:item><name>Takao Takeshima</name><affiliations><json:string>Department of Neurology and Neuropathology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683–8504, Japan</json:string></affiliations></json:item><json:item><name>Toshiya Nakano</name><affiliations><json:string>Department of Neurology and Neuropathology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683–8504, Japan</json:string></affiliations></json:item><json:item><name>Masaharu Tanaka</name><affiliations><json:string>Minase Research Institute, Ono Pharmaceutical Co., Ltd, Osaka 618–8585, Japan</json:string></affiliations></json:item><json:item><name>Katsuyoshi Sunaga</name><affiliations><json:string>Group on Cellular Neurobiology, Josai University, Sakado, Saitama 350–0248, Japan</json:string></affiliations></json:item><json:item><name>Yoko Fukuhara</name><affiliations><json:string>Department of Neurology and Neuropathology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683–8504, Japan</json:string></affiliations></json:item><json:item><name>Kenji Nakashima</name><affiliations><json:string>Department of Neurology and Neuropathology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683–8504, Japan</json:string></affiliations></json:item><json:item><name>Eisaku Ohama</name><affiliations><json:string>Department of Neurology and Neuropathology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683–8504, Japan</json:string></affiliations></json:item><json:item><name>Hideki Mochizuki</name><affiliations><json:string>Department of Neurology, Juntendo University School of Medicine, Tokyo 113–8421, Japan</json:string></affiliations></json:item><json:item><name>Yoshikuni Mizuno</name><affiliations><json:string>Department of Neurology, Juntendo University School of Medicine, Tokyo 113–8421, Japan</json:string></affiliations></json:item><json:item><name>Nobuo Katsube</name><affiliations><json:string>Minase Research Institute, Ono Pharmaceutical Co., Ltd, Osaka 618–8585, Japan</json:string></affiliations></json:item><json:item><name>Ryoichi Ishitani</name><affiliations><json:string>Group on Cellular Neurobiology, Josai University, Sakado, Saitama 350–0248, Japan</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>coaggregation</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Lewy bodies</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Parkinson's disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>pro‐apoptotic GAPDH</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>wild‐type α‐synuclein</value></json:item></subject><articleId><json:string>EJN3870</json:string></articleId><language><json:string>eng</json:string></language><abstract>Glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) has long been recognized as a classical glycolytic protein; however, previous studies by our group and others have demonstrated that GAPDH is a general mediator initiating one or more apoptotic cascades. Our most recent findings have elucidated that an expression of a pro‐apoptotic protein GAPDH is critically regulated at the promoter region of the gene. Apoptotic signals for its subsequent aggregate formation and nuclear translocation are controlled by the respective functional domains harboured within its cDNA component. In this study, coexpression of GAPDH with either wild‐type or mutant (A53T) α‐synuclein and less likely with β‐synuclein in transfected COS‐7 cells was found to induce Lewy body‐like cytoplasmic inclusions. Unlike its full‐length construct, the deleted mutant GAPDH construct (C66) abolished these apoptotic signals, disfavouring the formation of inclusions. The generated inclusions were ubiquitin‐ and thioflavin S‐positive appearing fibrils. Furthermore, GAPDH coimmunoprecipitated with wild‐type α‐synuclein in this paradigm. Importantly, immunohistochemical examinations of post mortem materials from patients with sporadic Parkinson's disease revealed the colocalized profiles immunoreactive against these two proteins in the peripheral zone of Lewy bodies from the affected brain regions (i.e. locus coeruleus). Moreover, a quantitative assessment showed that about 20% of Lewy bodies displayed both antigenicities. These results suggest that pro‐apoptotic protein GAPDH may be involved in the Lewy body formation in vivo, probably associated with the apoptotic death pathway.</abstract><qualityIndicators><score>8.176</score><pdfVersion>1.4</pdfVersion><pdfPageSize>595 x 782 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>5</keywordCount><abstractCharCount>1661</abstractCharCount><pdfWordCount>6074</pdfWordCount><pdfCharCount>40234</pdfCharCount><pdfPageCount>10</pdfPageCount><abstractWordCount>223</abstractWordCount></qualityIndicators><title>Pro‐apoptotic protein glyceraldehyde‐3‐phosphate dehydrogenase promotes the formation of Lewy body‐like inclusions</title><genre><json:string>article</json:string></genre><host><volume>21</volume><publisherId><json:string>EJN</json:string></publisherId><pages><total>10</total><last>326</last><first>317</first></pages><issn><json:string>0953-816X</json:string></issn><issue>2</issue><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1460-9568</json:string></eissn><title>European Journal of Neuroscience</title><doi><json:string>10.1111/(ISSN)1460-9568</json:string></doi></host><publicationDate>2005</publicationDate><copyrightDate>2005</copyrightDate><doi><json:string>10.1111/j.1460-9568.2005.03870.x</json:string></doi><id>0B7F2222CCCA27AAE1C98A644EB99EF5D6A3103D</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/0B7F2222CCCA27AAE1C98A644EB99EF5D6A3103D/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/0B7F2222CCCA27AAE1C98A644EB99EF5D6A3103D/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/0B7F2222CCCA27AAE1C98A644EB99EF5D6A3103D/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Pro‐apoptotic protein glyceraldehyde‐3‐phosphate dehydrogenase promotes the formation of Lewy body‐like inclusions</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Blackwell Science Ltd</publisher><pubPlace>Oxford, UK</pubPlace><availability><p>WILEY</p></availability><date>2005</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Pro‐apoptotic protein glyceraldehyde‐3‐phosphate dehydrogenase promotes the formation of Lewy body‐like inclusions</title><author><persName><forename type="first">Katsumi</forename><surname>Tsuchiya</surname></persName><note type="biography">K.T. and H.T. contributed equally to this work.</note><affiliation>K.T. and H.T. contributed equally to this work.</affiliation><affiliation>Group on Cellular Neurobiology, Josai University, Sakado, Saitama 350–0248, Japan</affiliation></author><author><persName><forename type="first">Hisao</forename><surname>Tajima</surname></persName><note type="biography">K.T. and H.T. contributed equally to this work.</note><affiliation>K.T. and H.T. contributed equally to this work.</affiliation><affiliation>Minase Research Institute, Ono Pharmaceutical Co., Ltd, Osaka 618–8585, Japan</affiliation></author><author><persName><forename type="first">Toyoyasu</forename><surname>Kuwae</surname></persName><affiliation>Group on Cellular Neurobiology, Josai University, Sakado, Saitama 350–0248, Japan</affiliation></author><author><persName><forename type="first">Takao</forename><surname>Takeshima</surname></persName><affiliation>Department of Neurology and Neuropathology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683–8504, Japan</affiliation></author><author><persName><forename type="first">Toshiya</forename><surname>Nakano</surname></persName><affiliation>Department of Neurology and Neuropathology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683–8504, Japan</affiliation></author><author><persName><forename type="first">Masaharu</forename><surname>Tanaka</surname></persName><affiliation>Minase Research Institute, Ono Pharmaceutical Co., Ltd, Osaka 618–8585, Japan</affiliation></author><author><persName><forename type="first">Katsuyoshi</forename><surname>Sunaga</surname></persName><affiliation>Group on Cellular Neurobiology, Josai University, Sakado, Saitama 350–0248, Japan</affiliation></author><author><persName><forename type="first">Yoko</forename><surname>Fukuhara</surname></persName><affiliation>Department of Neurology and Neuropathology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683–8504, Japan</affiliation></author><author><persName><forename type="first">Kenji</forename><surname>Nakashima</surname></persName><affiliation>Department of Neurology and Neuropathology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683–8504, Japan</affiliation></author><author><persName><forename type="first">Eisaku</forename><surname>Ohama</surname></persName><affiliation>Department of Neurology and Neuropathology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683–8504, Japan</affiliation></author><author><persName><forename type="first">Hideki</forename><surname>Mochizuki</surname></persName><affiliation>Department of Neurology, Juntendo University School of Medicine, Tokyo 113–8421, Japan</affiliation></author><author><persName><forename type="first">Yoshikuni</forename><surname>Mizuno</surname></persName><affiliation>Department of Neurology, Juntendo University School of Medicine, Tokyo 113–8421, Japan</affiliation></author><author><persName><forename type="first">Nobuo</forename><surname>Katsube</surname></persName><affiliation>Minase Research Institute, Ono Pharmaceutical Co., Ltd, Osaka 618–8585, Japan</affiliation></author><author><persName><forename type="first">Ryoichi</forename><surname>Ishitani</surname></persName><affiliation>Group on Cellular Neurobiology, Josai University, Sakado, Saitama 350–0248, Japan</affiliation></author></analytic><monogr><title level="j">European Journal of Neuroscience</title><idno type="pISSN">0953-816X</idno><idno type="eISSN">1460-9568</idno><idno type="DOI">10.1111/(ISSN)1460-9568</idno><imprint><publisher>Blackwell Science Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2005-01"></date><biblScope unit="volume">21</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="317">317</biblScope><biblScope unit="page" to="326">326</biblScope></imprint></monogr><idno type="istex">0B7F2222CCCA27AAE1C98A644EB99EF5D6A3103D</idno><idno type="DOI">10.1111/j.1460-9568.2005.03870.x</idno><idno type="ArticleID">EJN3870</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2005</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) has long been recognized as a classical glycolytic protein; however, previous studies by our group and others have demonstrated that GAPDH is a general mediator initiating one or more apoptotic cascades. Our most recent findings have elucidated that an expression of a pro‐apoptotic protein GAPDH is critically regulated at the promoter region of the gene. Apoptotic signals for its subsequent aggregate formation and nuclear translocation are controlled by the respective functional domains harboured within its cDNA component. In this study, coexpression of GAPDH with either wild‐type or mutant (A53T) α‐synuclein and less likely with β‐synuclein in transfected COS‐7 cells was found to induce Lewy body‐like cytoplasmic inclusions. Unlike its full‐length construct, the deleted mutant GAPDH construct (C66) abolished these apoptotic signals, disfavouring the formation of inclusions. The generated inclusions were ubiquitin‐ and thioflavin S‐positive appearing fibrils. Furthermore, GAPDH coimmunoprecipitated with wild‐type α‐synuclein in this paradigm. Importantly, immunohistochemical examinations of post mortem materials from patients with sporadic Parkinson's disease revealed the colocalized profiles immunoreactive against these two proteins in the peripheral zone of Lewy bodies from the affected brain regions (i.e. locus coeruleus). Moreover, a quantitative assessment showed that about 20% of Lewy bodies displayed both antigenicities. These results suggest that pro‐apoptotic protein GAPDH may be involved in the Lewy body formation in vivo, probably associated with the apoptotic death pathway.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>coaggregation</term></item><item><term>Lewy bodies</term></item><item><term>Parkinson's disease</term></item><item><term>pro‐apoptotic GAPDH</term></item><item><term>wild‐type α‐synuclein</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2005-01">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/0B7F2222CCCA27AAE1C98A644EB99EF5D6A3103D/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Blackwell Science Ltd</publisherName><publisherLoc>Oxford, UK</publisherLoc></publisherInfo><doi origin="wiley" registered="yes">10.1111/(ISSN)1460-9568</doi><issn type="print">0953-816X</issn><issn type="electronic">1460-9568</issn><idGroup><id type="product" value="EJN"></id><id type="publisherDivision" value="ST"></id></idGroup><titleGroup><title type="main" sort="EUROPEAN JOURNAL OF NEUROSCIENCE">European Journal of Neuroscience</title></titleGroup></publicationMeta><publicationMeta level="part" position="01002"><doi origin="wiley">10.1111/ejn.2005.21.issue-2</doi><numberingGroup><numbering type="journalVolume" number="21">21</numbering><numbering type="journalIssue" number="2">2</numbering></numberingGroup><coverDate startDate="2005-01">January 2005</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="2" status="forIssue"><doi origin="wiley">10.1111/j.1460-9568.2005.03870.x</doi><idGroup><id type="unit" value="EJN3870"></id></idGroup><countGroup><count type="pageTotal" number="10"></count></countGroup><titleGroup><title type="tocHeading1">Research Reports</title></titleGroup><eventGroup><event type="firstOnline" date="2005-01-20"></event><event type="publishedOnlineFinalForm" date="2005-01-26"></event><event type="xmlConverted" agent="Converter:BPG_TO_WML3G version:2.3.15 mode:FullText source:FullText result:FullText" date="2010-07-21"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:4.0.1" date="2014-03-12"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-16"></event></eventGroup><numberingGroup><numbering type="pageFirst" number="317">317</numbering><numbering type="pageLast" number="326">326</numbering></numberingGroup><correspondenceTo>Dr R. Ishitani, as above.
E‐mail: <email>ishitani@josai.ac.jp</email></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:EJN.EJN3870.pdf"></link></linkGroup></publicationMeta><contentMeta><unparsedEditorialHistory>Received 27 July 2004, revised 07 November 2004, accepted 10 November 2004</unparsedEditorialHistory><countGroup><count type="figureTotal" number="6"></count><count type="tableTotal" number="0"></count><count type="formulaTotal" number="0"></count><count type="referenceTotal" number="41"></count><count type="wordTotal" number="5519"></count><count type="linksPubMed" number="0"></count><count type="linksCrossRef" number="0"></count></countGroup><titleGroup><title type="main">Pro‐apoptotic protein glyceraldehyde‐3‐phosphate dehydrogenase promotes the formation of Lewy body‐like inclusions</title><title type="shortAuthors">K. Tsuchiya <i>et al</i>.</title><title type="short">Involvement of GAPDH in Lewy body formation</title></titleGroup><creators><creator creatorRole="author" xml:id="cr1" affiliationRef="#a1" noteRef="#fn1"><personName><givenNames>Katsumi</givenNames><familyName>Tsuchiya</familyName></personName></creator><creator creatorRole="author" xml:id="cr2" affiliationRef="#a2" noteRef="#fn1"><personName><givenNames>Hisao</givenNames><familyName>Tajima</familyName></personName></creator><creator creatorRole="author" xml:id="cr3" affiliationRef="#a1"><personName><givenNames>Toyoyasu</givenNames><familyName>Kuwae</familyName></personName></creator><creator creatorRole="author" xml:id="cr4" affiliationRef="#a3"><personName><givenNames>Takao</givenNames><familyName>Takeshima</familyName></personName></creator><creator creatorRole="author" xml:id="cr5" affiliationRef="#a3"><personName><givenNames>Toshiya</givenNames><familyName>Nakano</familyName></personName></creator><creator creatorRole="author" xml:id="cr6" affiliationRef="#a2"><personName><givenNames>Masaharu</givenNames><familyName>Tanaka</familyName></personName></creator><creator creatorRole="author" xml:id="cr7" affiliationRef="#a1"><personName><givenNames>Katsuyoshi</givenNames><familyName>Sunaga</familyName></personName></creator><creator creatorRole="author" xml:id="cr8" affiliationRef="#a3"><personName><givenNames>Yoko</givenNames><familyName>Fukuhara</familyName></personName></creator><creator creatorRole="author" xml:id="cr9" affiliationRef="#a3"><personName><givenNames>Kenji</givenNames><familyName>Nakashima</familyName></personName></creator><creator creatorRole="author" xml:id="cr10" affiliationRef="#a3"><personName><givenNames>Eisaku</givenNames><familyName>Ohama</familyName></personName></creator><creator creatorRole="author" xml:id="cr11" affiliationRef="#a4"><personName><givenNames>Hideki</givenNames><familyName>Mochizuki</familyName></personName></creator><creator creatorRole="author" xml:id="cr12" affiliationRef="#a4"><personName><givenNames>Yoshikuni</givenNames><familyName>Mizuno</familyName></personName></creator><creator creatorRole="author" xml:id="cr13" affiliationRef="#a2"><personName><givenNames>Nobuo</givenNames><familyName>Katsube</familyName></personName></creator><creator creatorRole="author" xml:id="cr14" affiliationRef="#a1"><personName><givenNames>Ryoichi</givenNames><familyName>Ishitani</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="a1" countryCode="JP"><unparsedAffiliation>Group on Cellular Neurobiology, Josai University, Sakado, Saitama 350–0248, Japan</unparsedAffiliation></affiliation><affiliation xml:id="a2" countryCode="JP"><unparsedAffiliation>Minase Research Institute, Ono Pharmaceutical Co., Ltd, Osaka 618–8585, Japan</unparsedAffiliation></affiliation><affiliation xml:id="a3" countryCode="JP"><unparsedAffiliation>Department of Neurology and Neuropathology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683–8504, Japan</unparsedAffiliation></affiliation><affiliation xml:id="a4" countryCode="JP"><unparsedAffiliation>Department of Neurology, Juntendo University School of Medicine, Tokyo 113–8421, Japan</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en"><keyword xml:id="k1">coaggregation</keyword><keyword xml:id="k2">Lewy bodies</keyword><keyword xml:id="k3">Parkinson's disease</keyword><keyword xml:id="k4">pro‐apoptotic GAPDH</keyword><keyword xml:id="k5">wild‐type α‐synuclein</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) has long been recognized as a classical glycolytic protein; however, previous studies by our group and others have demonstrated that GAPDH is a general mediator initiating one or more apoptotic cascades. Our most recent findings have elucidated that an expression of a pro‐apoptotic protein GAPDH is critically regulated at the promoter region of the gene. Apoptotic signals for its subsequent aggregate formation and nuclear translocation are controlled by the respective functional domains harboured within its cDNA component. In this study, coexpression of GAPDH with either wild‐type or mutant (A53T) α‐synuclein and less likely with β‐synuclein in transfected COS‐7 cells was found to induce Lewy body‐like cytoplasmic inclusions. Unlike its full‐length construct, the deleted mutant GAPDH construct (C66) abolished these apoptotic signals, disfavouring the formation of inclusions. The generated inclusions were ubiquitin‐ and thioflavin S‐positive appearing fibrils. Furthermore, GAPDH coimmunoprecipitated with wild‐type α‐synuclein in this paradigm. Importantly, immunohistochemical examinations of post mortem materials from patients with sporadic Parkinson's disease revealed the colocalized profiles immunoreactive against these two proteins in the peripheral zone of Lewy bodies from the affected brain regions (i.e. locus coeruleus). Moreover, a quantitative assessment showed that about 20% of Lewy bodies displayed both antigenicities. These results suggest that pro‐apoptotic protein GAPDH may be involved in the Lewy body formation <i>in vivo,</i> probably associated with the apoptotic death pathway.</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><label>*</label><p> K.T. and H.T. contributed equally to this work.</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Pro‐apoptotic protein glyceraldehyde‐3‐phosphate dehydrogenase promotes the formation of Lewy body‐like inclusions</title></titleInfo><titleInfo type="abbreviated"><title>Involvement of GAPDH in Lewy body formation</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Pro‐apoptotic protein glyceraldehyde‐3‐phosphate dehydrogenase promotes the formation of Lewy body‐like inclusions</title></titleInfo><name type="personal"><namePart type="given">Katsumi</namePart><namePart type="family">Tsuchiya</namePart><affiliation>Group on Cellular Neurobiology, Josai University, Sakado, Saitama 350–0248, Japan</affiliation><description>K.T. and H.T. contributed equally to this work.</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Hisao</namePart><namePart type="family">Tajima</namePart><affiliation>Minase Research Institute, Ono Pharmaceutical Co., Ltd, Osaka 618–8585, Japan</affiliation><description>K.T. and H.T. contributed equally to this work.</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Toyoyasu</namePart><namePart type="family">Kuwae</namePart><affiliation>Group on Cellular Neurobiology, Josai University, Sakado, Saitama 350–0248, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Takao</namePart><namePart type="family">Takeshima</namePart><affiliation>Department of Neurology and Neuropathology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683–8504, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Toshiya</namePart><namePart type="family">Nakano</namePart><affiliation>Department of Neurology and Neuropathology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683–8504, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Masaharu</namePart><namePart type="family">Tanaka</namePart><affiliation>Minase Research Institute, Ono Pharmaceutical Co., Ltd, Osaka 618–8585, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Katsuyoshi</namePart><namePart type="family">Sunaga</namePart><affiliation>Group on Cellular Neurobiology, Josai University, Sakado, Saitama 350–0248, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Yoko</namePart><namePart type="family">Fukuhara</namePart><affiliation>Department of Neurology and Neuropathology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683–8504, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Kenji</namePart><namePart type="family">Nakashima</namePart><affiliation>Department of Neurology and Neuropathology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683–8504, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Eisaku</namePart><namePart type="family">Ohama</namePart><affiliation>Department of Neurology and Neuropathology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, Yonago 683–8504, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Hideki</namePart><namePart type="family">Mochizuki</namePart><affiliation>Department of Neurology, Juntendo University School of Medicine, Tokyo 113–8421, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Yoshikuni</namePart><namePart type="family">Mizuno</namePart><affiliation>Department of Neurology, Juntendo University School of Medicine, Tokyo 113–8421, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Nobuo</namePart><namePart type="family">Katsube</namePart><affiliation>Minase Research Institute, Ono Pharmaceutical Co., Ltd, Osaka 618–8585, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ryoichi</namePart><namePart type="family">Ishitani</namePart><affiliation>Group on Cellular Neurobiology, Josai University, Sakado, Saitama 350–0248, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Blackwell Science Ltd</publisher><place><placeTerm type="text">Oxford, UK</placeTerm></place><dateIssued encoding="w3cdtf">2005-01</dateIssued><edition>Received 27 July 2004, revised 07 November 2004, accepted 10 November 2004</edition><copyrightDate encoding="w3cdtf">2005</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">6</extent><extent unit="references">41</extent><extent unit="words">5519</extent></physicalDescription><abstract lang="en">Glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) has long been recognized as a classical glycolytic protein; however, previous studies by our group and others have demonstrated that GAPDH is a general mediator initiating one or more apoptotic cascades. Our most recent findings have elucidated that an expression of a pro‐apoptotic protein GAPDH is critically regulated at the promoter region of the gene. Apoptotic signals for its subsequent aggregate formation and nuclear translocation are controlled by the respective functional domains harboured within its cDNA component. In this study, coexpression of GAPDH with either wild‐type or mutant (A53T) α‐synuclein and less likely with β‐synuclein in transfected COS‐7 cells was found to induce Lewy body‐like cytoplasmic inclusions. Unlike its full‐length construct, the deleted mutant GAPDH construct (C66) abolished these apoptotic signals, disfavouring the formation of inclusions. The generated inclusions were ubiquitin‐ and thioflavin S‐positive appearing fibrils. Furthermore, GAPDH coimmunoprecipitated with wild‐type α‐synuclein in this paradigm. Importantly, immunohistochemical examinations of post mortem materials from patients with sporadic Parkinson's disease revealed the colocalized profiles immunoreactive against these two proteins in the peripheral zone of Lewy bodies from the affected brain regions (i.e. locus coeruleus). Moreover, a quantitative assessment showed that about 20% of Lewy bodies displayed both antigenicities. These results suggest that pro‐apoptotic protein GAPDH may be involved in the Lewy body formation in vivo, probably associated with the apoptotic death pathway.</abstract><subject lang="en"><genre>Keywords</genre><topic>coaggregation</topic><topic>Lewy bodies</topic><topic>Parkinson's disease</topic><topic>pro‐apoptotic GAPDH</topic><topic>wild‐type α‐synuclein</topic></subject><relatedItem type="host"><titleInfo><title>European Journal of Neuroscience</title></titleInfo><genre type="Journal">journal</genre><identifier type="ISSN">0953-816X</identifier><identifier type="eISSN">1460-9568</identifier><identifier type="DOI">10.1111/(ISSN)1460-9568</identifier><identifier type="PublisherID">EJN</identifier><part><date>2005</date><detail type="volume"><caption>vol.</caption><number>21</number></detail><detail type="issue"><caption>no.</caption><number>2</number></detail><extent unit="pages"><start>317</start><end>326</end><total>10</total></extent></part></relatedItem><identifier type="istex">0B7F2222CCCA27AAE1C98A644EB99EF5D6A3103D</identifier><identifier type="DOI">10.1111/j.1460-9568.2005.03870.x</identifier><identifier type="ArticleID">EJN3870</identifier><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Blackwell Science Ltd</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonV1/Data/Main/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002680 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Corpus/biblio.hfd -nk 002680 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonV1
|flux= Main
|étape= Corpus
|type= RBID
|clé= ISTEX:0B7F2222CCCA27AAE1C98A644EB99EF5D6A3103D
|texte= Pro‐apoptotic protein glyceraldehyde‐3‐phosphate dehydrogenase promotes the formation of Lewy body‐like inclusions
}}
| This area was generated with Dilib version V0.6.23. |  |