Molecular Alterations in the Cerebellum of Sporadic Creutzfeldt-Jakob Disease Subtypes with DJ-1 as a Key Regulator of Oxidative Stress.
Identifieur interne : 000044 ( PubMed/Corpus ); précédent : 000043; suivant : 000045Molecular Alterations in the Cerebellum of Sporadic Creutzfeldt-Jakob Disease Subtypes with DJ-1 as a Key Regulator of Oxidative Stress.
Auteurs : Waqas Tahir ; Saima Zafar ; Franc Llorens ; Amandeep Singh Arora ; Katrin Thüne ; Matthias Schmitz ; Nadine Gotzmann ; Niels Kruse ; Brit Mollenhauer ; Juan Maria Torres ; Olivier Andréoletti ; Isidre Ferrer ; Inga ZerrSource :
- Molecular neurobiology [ 1559-1182 ] ; 2016.
Abstract
Cerebellar damage and granular and Purkinje cell loss in sporadic Creutzfeldt-Jakob disease (sCJD) highlight a critical involvement of the cerebellum during symptomatic progression of the disease. In this project, global proteomic alterations in the cerebellum of brain from the two most prevalent subtypes (MM1 and VV2) of sCJD were studied. Two-dimensional gel electrophoresis (2DE) coupled mass spectrometric identification revealed 40 proteins in MM1 and 43 proteins in VV2 subtype to be differentially expressed. Of those, 12 proteins showed common differential expression in their expression between two subtypes. Differentially expressed proteins mainly belonged to (i) cell cycle, gene expression and cell death; (ii) cellular stress response/oxidative stress (OS) and (iii) signal transduction and synaptic functions, related molecular functions. We verified 10 differentially expressed proteins at transcriptional and translational level as well. Interestingly, protein deglycase DJ-1 (an antioxidative protein) showed an increase in its messenger RNA (mRNA) expression in both MM1 and VV2 subtypes but protein expression only in VV2 subtype in cerebellum of sCJD patients. Nuclear translocalization of DJ-1 confirmed its expressional alteration due to OS in sCJD. Downstream experiments showed the activation of nuclear factor erythroid-2 related factor 2 (Nrf2)/antioxidative response element (ARE) pathway. DJ-1 protein concentration was significantly increased during the clinical phase in cerebrospinal fluid of sCJD patients and also at presymptomatic and symptomatic stages in cerebellum of humanized PrP transgenic mice inoculated with sCJD (MM1 and VV2) brain. These results suggest the implication of oxidative stress during the pathophysiology of sCJD.
DOI: 10.1007/s12035-016-0294-4
PubMed: 27975168
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sort="Kruse, Niels" uniqKey="Kruse N" first="Niels" last="Kruse">Niels Kruse</name><affiliation><nlm:affiliation>Institute of Neuropathology, University Medical Center Goettingen (UMG), Robert-Koch-Str. 40, 37075, Goettingen, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Mollenhauer, Brit" sort="Mollenhauer, Brit" uniqKey="Mollenhauer B" first="Brit" last="Mollenhauer">Brit Mollenhauer</name><affiliation><nlm:affiliation>Institute of Neuropathology, University Medical Center Goettingen (UMG), Robert-Koch-Str. 40, 37075, Goettingen, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Torres, Juan Maria" sort="Torres, Juan Maria" uniqKey="Torres J" first="Juan Maria" last="Torres">Juan Maria Torres</name><affiliation><nlm:affiliation>Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Carretera de Algete a El Casar Km. 8,1 S/N, 28130, Valdeolmos, Madrid, Spain.</nlm:affiliation></affiliation></author><author><name sortKey="Andreoletti, Olivier" sort="Andreoletti, Olivier" uniqKey="Andreoletti O" first="Olivier" last="Andréoletti">Olivier Andréoletti</name><affiliation><nlm:affiliation>Institut National de la Recherche Agronomique/Ecole Nationale Vétérinaire, Toulouse, France.</nlm:affiliation></affiliation></author><author><name sortKey="Ferrer, Isidre" sort="Ferrer, Isidre" uniqKey="Ferrer I" first="Isidre" last="Ferrer">Isidre Ferrer</name><affiliation><nlm:affiliation>Institute of Neuropathology, Hospitalet de Llobregat, IDIBELL-University Hospital Bellvitge, University of Barcelona, Barcelona, Spain.</nlm:affiliation></affiliation></author><author><name sortKey="Zerr, Inga" sort="Zerr, Inga" uniqKey="Zerr I" first="Inga" last="Zerr">Inga Zerr</name><affiliation><nlm:affiliation>Department of Neurology, University Medical Center Goettingen (UMG) and German Center for Neurodegenerative Diseases (DZNE) Goettingen, Robert-Koch-Str., 40, 37075, Goettingen, Germany.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:27975168</idno><idno type="pmid">27975168</idno><idno type="doi">10.1007/s12035-016-0294-4</idno><idno type="wicri:Area/PubMed/Corpus">000044</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000044</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Molecular Alterations in the Cerebellum of Sporadic Creutzfeldt-Jakob Disease Subtypes with DJ-1 as a Key Regulator of Oxidative Stress.</title><author><name sortKey="Tahir, Waqas" sort="Tahir, Waqas" uniqKey="Tahir W" first="Waqas" last="Tahir">Waqas Tahir</name><affiliation><nlm:affiliation>Department of Neurology, University Medical Center Goettingen (UMG) and German Center for Neurodegenerative Diseases (DZNE) Goettingen, Robert-Koch-Str., 40, 37075, Goettingen, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Zafar, Saima" sort="Zafar, Saima" uniqKey="Zafar S" first="Saima" last="Zafar">Saima Zafar</name><affiliation><nlm:affiliation>Department of Neurology, University Medical Center Goettingen (UMG) and German Center for Neurodegenerative Diseases (DZNE) Goettingen, Robert-Koch-Str., 40, 37075, Goettingen, Germany. sz_awaan@yahoo.com.</nlm:affiliation></affiliation></author><author><name sortKey="Llorens, Franc" sort="Llorens, Franc" uniqKey="Llorens F" first="Franc" last="Llorens">Franc Llorens</name><affiliation><nlm:affiliation>Department of Neurology, University Medical Center Goettingen (UMG) and German Center for Neurodegenerative Diseases (DZNE) Goettingen, Robert-Koch-Str., 40, 37075, Goettingen, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Arora, Amandeep Singh" sort="Arora, Amandeep Singh" uniqKey="Arora A" first="Amandeep Singh" last="Arora">Amandeep Singh Arora</name><affiliation><nlm:affiliation>Department of Neurology, University Medical Center Goettingen (UMG) and German Center for Neurodegenerative Diseases (DZNE) Goettingen, Robert-Koch-Str., 40, 37075, Goettingen, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Thune, Katrin" sort="Thune, Katrin" uniqKey="Thune K" first="Katrin" last="Thüne">Katrin Thüne</name><affiliation><nlm:affiliation>Department of Neurology, University Medical Center Goettingen (UMG) and German Center for Neurodegenerative Diseases (DZNE) Goettingen, Robert-Koch-Str., 40, 37075, Goettingen, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Schmitz, Matthias" sort="Schmitz, Matthias" uniqKey="Schmitz M" first="Matthias" last="Schmitz">Matthias Schmitz</name><affiliation><nlm:affiliation>Department of Neurology, University Medical Center Goettingen (UMG) and German Center for Neurodegenerative Diseases (DZNE) Goettingen, Robert-Koch-Str., 40, 37075, Goettingen, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Gotzmann, Nadine" sort="Gotzmann, Nadine" uniqKey="Gotzmann N" first="Nadine" last="Gotzmann">Nadine Gotzmann</name><affiliation><nlm:affiliation>Department of Neurology, University Medical Center Goettingen (UMG) and German Center for Neurodegenerative Diseases (DZNE) Goettingen, Robert-Koch-Str., 40, 37075, Goettingen, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Kruse, Niels" sort="Kruse, Niels" uniqKey="Kruse N" first="Niels" last="Kruse">Niels Kruse</name><affiliation><nlm:affiliation>Institute of Neuropathology, University Medical Center Goettingen (UMG), Robert-Koch-Str. 40, 37075, Goettingen, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Mollenhauer, Brit" sort="Mollenhauer, Brit" uniqKey="Mollenhauer B" first="Brit" last="Mollenhauer">Brit Mollenhauer</name><affiliation><nlm:affiliation>Institute of Neuropathology, University Medical Center Goettingen (UMG), Robert-Koch-Str. 40, 37075, Goettingen, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Torres, Juan Maria" sort="Torres, Juan Maria" uniqKey="Torres J" first="Juan Maria" last="Torres">Juan Maria Torres</name><affiliation><nlm:affiliation>Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Carretera de Algete a El Casar Km. 8,1 S/N, 28130, Valdeolmos, Madrid, Spain.</nlm:affiliation></affiliation></author><author><name sortKey="Andreoletti, Olivier" sort="Andreoletti, Olivier" uniqKey="Andreoletti O" first="Olivier" last="Andréoletti">Olivier Andréoletti</name><affiliation><nlm:affiliation>Institut National de la Recherche Agronomique/Ecole Nationale Vétérinaire, Toulouse, France.</nlm:affiliation></affiliation></author><author><name sortKey="Ferrer, Isidre" sort="Ferrer, Isidre" uniqKey="Ferrer I" first="Isidre" last="Ferrer">Isidre Ferrer</name><affiliation><nlm:affiliation>Institute of Neuropathology, Hospitalet de Llobregat, IDIBELL-University Hospital Bellvitge, University of Barcelona, Barcelona, Spain.</nlm:affiliation></affiliation></author><author><name sortKey="Zerr, Inga" sort="Zerr, Inga" uniqKey="Zerr I" first="Inga" last="Zerr">Inga Zerr</name><affiliation><nlm:affiliation>Department of Neurology, University Medical Center Goettingen (UMG) and German Center for Neurodegenerative Diseases (DZNE) Goettingen, Robert-Koch-Str., 40, 37075, Goettingen, Germany.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Molecular neurobiology</title><idno type="eISSN">1559-1182</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Cerebellar damage and granular and Purkinje cell loss in sporadic Creutzfeldt-Jakob disease (sCJD) highlight a critical involvement of the cerebellum during symptomatic progression of the disease. In this project, global proteomic alterations in the cerebellum of brain from the two most prevalent subtypes (MM1 and VV2) of sCJD were studied. Two-dimensional gel electrophoresis (2DE) coupled mass spectrometric identification revealed 40 proteins in MM1 and 43 proteins in VV2 subtype to be differentially expressed. Of those, 12 proteins showed common differential expression in their expression between two subtypes. Differentially expressed proteins mainly belonged to (i) cell cycle, gene expression and cell death; (ii) cellular stress response/oxidative stress (OS) and (iii) signal transduction and synaptic functions, related molecular functions. We verified 10 differentially expressed proteins at transcriptional and translational level as well. Interestingly, protein deglycase DJ-1 (an antioxidative protein) showed an increase in its messenger RNA (mRNA) expression in both MM1 and VV2 subtypes but protein expression only in VV2 subtype in cerebellum of sCJD patients. Nuclear translocalization of DJ-1 confirmed its expressional alteration due to OS in sCJD. Downstream experiments showed the activation of nuclear factor erythroid-2 related factor 2 (Nrf2)/antioxidative response element (ARE) pathway. DJ-1 protein concentration was significantly increased during the clinical phase in cerebrospinal fluid of sCJD patients and also at presymptomatic and symptomatic stages in cerebellum of humanized PrP transgenic mice inoculated with sCJD (MM1 and VV2) brain. These results suggest the implication of oxidative stress during the pathophysiology of sCJD.</div></front></TEI><pubmed><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">27975168</PMID><DateCreated><Year>2016</Year><Month>12</Month><Day>15</Day></DateCreated><DateRevised><Year>2016</Year><Month>12</Month><Day>16</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1559-1182</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2016</Year><Month>Dec</Month><Day>14</Day></PubDate></JournalIssue><Title>Molecular neurobiology</Title><ISOAbbreviation>Mol. Neurobiol.</ISOAbbreviation></Journal><ArticleTitle>Molecular Alterations in the Cerebellum of Sporadic Creutzfeldt-Jakob Disease Subtypes with DJ-1 as a Key Regulator of Oxidative Stress.</ArticleTitle><Pagination><MedlinePgn></MedlinePgn></Pagination><Abstract><AbstractText NlmCategory="UNASSIGNED">Cerebellar damage and granular and Purkinje cell loss in sporadic Creutzfeldt-Jakob disease (sCJD) highlight a critical involvement of the cerebellum during symptomatic progression of the disease. In this project, global proteomic alterations in the cerebellum of brain from the two most prevalent subtypes (MM1 and VV2) of sCJD were studied. Two-dimensional gel electrophoresis (2DE) coupled mass spectrometric identification revealed 40 proteins in MM1 and 43 proteins in VV2 subtype to be differentially expressed. Of those, 12 proteins showed common differential expression in their expression between two subtypes. Differentially expressed proteins mainly belonged to (i) cell cycle, gene expression and cell death; (ii) cellular stress response/oxidative stress (OS) and (iii) signal transduction and synaptic functions, related molecular functions. We verified 10 differentially expressed proteins at transcriptional and translational level as well. Interestingly, protein deglycase DJ-1 (an antioxidative protein) showed an increase in its messenger RNA (mRNA) expression in both MM1 and VV2 subtypes but protein expression only in VV2 subtype in cerebellum of sCJD patients. Nuclear translocalization of DJ-1 confirmed its expressional alteration due to OS in sCJD. Downstream experiments showed the activation of nuclear factor erythroid-2 related factor 2 (Nrf2)/antioxidative response element (ARE) pathway. DJ-1 protein concentration was significantly increased during the clinical phase in cerebrospinal fluid of sCJD patients and also at presymptomatic and symptomatic stages in cerebellum of humanized PrP transgenic mice inoculated with sCJD (MM1 and VV2) brain. These results suggest the implication of oxidative stress during the pathophysiology of sCJD.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Tahir</LastName><ForeName>Waqas</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Department of Neurology, University Medical Center Goettingen (UMG) and German Center for Neurodegenerative Diseases (DZNE) Goettingen, Robert-Koch-Str., 40, 37075, Goettingen, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zafar</LastName><ForeName>Saima</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Neurology, University Medical Center Goettingen (UMG) and German Center for Neurodegenerative Diseases (DZNE) Goettingen, Robert-Koch-Str., 40, 37075, Goettingen, Germany. sz_awaan@yahoo.com.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Llorens</LastName><ForeName>Franc</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Department of Neurology, University Medical Center Goettingen (UMG) and German Center for Neurodegenerative Diseases (DZNE) Goettingen, Robert-Koch-Str., 40, 37075, Goettingen, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Arora</LastName><ForeName>Amandeep Singh</ForeName><Initials>AS</Initials><AffiliationInfo><Affiliation>Department of Neurology, University Medical Center Goettingen (UMG) and German Center for Neurodegenerative Diseases (DZNE) Goettingen, Robert-Koch-Str., 40, 37075, Goettingen, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Thüne</LastName><ForeName>Katrin</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Neurology, University Medical Center Goettingen (UMG) and German Center for Neurodegenerative Diseases (DZNE) Goettingen, Robert-Koch-Str., 40, 37075, Goettingen, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schmitz</LastName><ForeName>Matthias</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Neurology, University Medical Center Goettingen (UMG) and German Center for Neurodegenerative Diseases (DZNE) Goettingen, Robert-Koch-Str., 40, 37075, Goettingen, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gotzmann</LastName><ForeName>Nadine</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Neurology, University Medical Center Goettingen (UMG) and German Center for Neurodegenerative Diseases (DZNE) Goettingen, Robert-Koch-Str., 40, 37075, Goettingen, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kruse</LastName><ForeName>Niels</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Institute of Neuropathology, University Medical Center Goettingen (UMG), Robert-Koch-Str. 40, 37075, Goettingen, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mollenhauer</LastName><ForeName>Brit</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Institute of Neuropathology, University Medical Center Goettingen (UMG), Robert-Koch-Str. 40, 37075, Goettingen, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Torres</LastName><ForeName>Juan Maria</ForeName><Initials>JM</Initials><AffiliationInfo><Affiliation>Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Carretera de Algete a El Casar Km. 8,1 S/N, 28130, Valdeolmos, Madrid, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Andréoletti</LastName><ForeName>Olivier</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>Institut National de la Recherche Agronomique/Ecole Nationale Vétérinaire, Toulouse, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ferrer</LastName><ForeName>Isidre</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Institute of Neuropathology, Hospitalet de Llobregat, IDIBELL-University Hospital Bellvitge, University of Barcelona, Barcelona, Spain.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Network Center for Biomedical Research of Neurodegenerative Diseases (CIBERNED), Ministry of Health, Institute Carlos III, Madrid, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zerr</LastName><ForeName>Inga</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Department of Neurology, University Medical Center Goettingen (UMG) and German Center for Neurodegenerative Diseases (DZNE) Goettingen, Robert-Koch-Str., 40, 37075, Goettingen, Germany.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>12</Month><Day>14</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Mol Neurobiol</MedlineTA><NlmUniqueID>8900963</NlmUniqueID><ISSNLinking>0893-7648</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Antioxidative response elements</Keyword><Keyword MajorTopicYN="N">Mass spectrometry</Keyword><Keyword MajorTopicYN="N">Parkinson disease protein 7/protein deglycase DJ-1</Keyword><Keyword MajorTopicYN="N">Sporadic Creutzfeldt–Jakob disease</Keyword><Keyword MajorTopicYN="N">Two-dimensional gel electrophoresis</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>09</Month><Day>02</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2016</Year><Month>11</Month><Day>08</Day></PubMedPubDate><PubMedPubDate 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