Concerted action of dipeptidyl peptidase IV and glutaminyl cyclase results in formation of pyroglutamate-modified amyloid peptides in vitro
Compelling evidence suggests a crucial role of amyloid beta peptides (Aβ(1-40/42)) in the etiology of Alzheimer's disease (AD). The N-terminal truncation of Aβ(1-40/42) and their modification, e.g. by glutaminyl cyclase (QC), is expected to enhance the amyloid toxicity. In this work, the MALDI-...
Gespeichert in:
Veröffentlicht in: | Neurochemistry international 2018-02, Vol.113, p.112-119 |
---|---|
Hauptverfasser: | , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 119 |
---|---|
container_issue | |
container_start_page | 112 |
container_title | Neurochemistry international |
container_volume | 113 |
creator | Antonyan, Alvard Schlenzig, Dagmar Schilling, Stephan Naumann, Marcel Sharoyan, Svetlana Mardanyan, Sona Demuth, Hans-Ulrich |
description | Compelling evidence suggests a crucial role of amyloid beta peptides (Aβ(1-40/42)) in the etiology of Alzheimer's disease (AD). The N-terminal truncation of Aβ(1-40/42) and their modification, e.g. by glutaminyl cyclase (QC), is expected to enhance the amyloid toxicity. In this work, the MALDI-TOF mass spectrometry application proved N-terminal cleavage of Aβ(1-40/42) by purified dipeptidyl peptidase IV (DPPIV) in vitro observed earlier. The subsequent transformation of resulted Aβ(3-40/42) to pE-Aβ(3-40/42) in QC catalyzed glutamate cyclization was manifested. Hence, consecutive conversion of Aβ(1-40/42) by DPPIV and QC can be assumed as a potential mechanism of formation of non-degrading pyroglutamated pE-Aβ(3-40/42), which might accumulate and contribute to AD progression. The in vitro acceleration of Aβ(1-40) aggregation in the simultaneous presence of DPPIV and QC was shown also.
•MALDI-TOF analysis proved N-terminal dipeptide cleavage from Aβ(1-40/42) by DPPIV.•Action of DPPIV is followed by QC catalyzed transformation to pE-Aβ(3-40/42) in vitro.•The aggregation of Aβ(1-40/42) is hindered by DPPIV and accelerated by QC in vitro. |
doi_str_mv | 10.1016/j.neuint.2017.12.001 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1975594380</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S019701861730462X</els_id><sourcerecordid>1975594380</sourcerecordid><originalsourceid>FETCH-LOGICAL-c362t-8fc1f90b6948a3f5072e8ac7e9732b25c2612ac93bf25e40527dec80f7fbb65e3</originalsourceid><addsrcrecordid>eNp9kU1q3TAQx0VpaF7S3qAULbuxK8mWZW0K5ZG2gUA2abdClkZFD9tyJTngO_QQPUtOVhu_ZNmVBPP_YOaH0HtKSkpo8-lUjjD7MZeMUFFSVhJCX6EDbQUrpOD1a3QgVIqC0La5RFcpnQghQhL-Bl0yyVgtG35Af45hNBAzWKxN9mHEwWHrJ5iyt0uP949OgG9_Yj1a_Kufsx78uM7MYvptEiHNfU7Yj9iFOOjnmGmJYZfrDMUQrHd-6xmWPnh7jobN9_T30ecY3qILp_sE787vNfrx9ebh-L24u_92e_xyV5iqYblonaFOkq6Rdasrx4lg0GojQIqKdYwb1lCmjaw6xzjUhDNhwbTECdd1DYfqGn3cc6cYfs-Qshp8MtD3eoQwJ7WejXNZVy1ZpfUuNTGkFMGpKfpBx0VRojYO6qR2DmrjoChTK4fV9uHcMHcD2BfT8-FXweddAOuejx6iSsbDisL6CCYrG_z_G_4B53agGw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1975594380</pqid></control><display><type>article</type><title>Concerted action of dipeptidyl peptidase IV and glutaminyl cyclase results in formation of pyroglutamate-modified amyloid peptides in vitro</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Antonyan, Alvard ; Schlenzig, Dagmar ; Schilling, Stephan ; Naumann, Marcel ; Sharoyan, Svetlana ; Mardanyan, Sona ; Demuth, Hans-Ulrich</creator><creatorcontrib>Antonyan, Alvard ; Schlenzig, Dagmar ; Schilling, Stephan ; Naumann, Marcel ; Sharoyan, Svetlana ; Mardanyan, Sona ; Demuth, Hans-Ulrich</creatorcontrib><description>Compelling evidence suggests a crucial role of amyloid beta peptides (Aβ(1-40/42)) in the etiology of Alzheimer's disease (AD). The N-terminal truncation of Aβ(1-40/42) and their modification, e.g. by glutaminyl cyclase (QC), is expected to enhance the amyloid toxicity. In this work, the MALDI-TOF mass spectrometry application proved N-terminal cleavage of Aβ(1-40/42) by purified dipeptidyl peptidase IV (DPPIV) in vitro observed earlier. The subsequent transformation of resulted Aβ(3-40/42) to pE-Aβ(3-40/42) in QC catalyzed glutamate cyclization was manifested. Hence, consecutive conversion of Aβ(1-40/42) by DPPIV and QC can be assumed as a potential mechanism of formation of non-degrading pyroglutamated pE-Aβ(3-40/42), which might accumulate and contribute to AD progression. The in vitro acceleration of Aβ(1-40) aggregation in the simultaneous presence of DPPIV and QC was shown also.
•MALDI-TOF analysis proved N-terminal dipeptide cleavage from Aβ(1-40/42) by DPPIV.•Action of DPPIV is followed by QC catalyzed transformation to pE-Aβ(3-40/42) in vitro.•The aggregation of Aβ(1-40/42) is hindered by DPPIV and accelerated by QC in vitro.</description><identifier>ISSN: 0197-0186</identifier><identifier>EISSN: 1872-9754</identifier><identifier>DOI: 10.1016/j.neuint.2017.12.001</identifier><identifier>PMID: 29224965</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Amino Acid Sequence ; Aminoacyltransferases - metabolism ; Amyloid beta peptides ; Amyloid beta-Peptides - analysis ; Amyloid beta-Peptides - genetics ; Amyloid beta-Peptides - metabolism ; Animals ; Cattle ; Dipeptidyl Peptidase 4 - metabolism ; Dipeptidyl peptidase IV ; Enzyme-substrate interactions ; Glutaminyl cyclase ; Humans ; MALDI-TOF mass spectrometry ; Peptide Fragments - analysis ; Peptide Fragments - genetics ; Peptide Fragments - metabolism ; Protein Aggregates - drug effects ; Protein Aggregates - physiology ; Pyrrolidonecarboxylic Acid - pharmacology ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods</subject><ispartof>Neurochemistry international, 2018-02, Vol.113, p.112-119</ispartof><rights>2017</rights><rights>Copyright © 2017. Published by Elsevier Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-8fc1f90b6948a3f5072e8ac7e9732b25c2612ac93bf25e40527dec80f7fbb65e3</citedby><cites>FETCH-LOGICAL-c362t-8fc1f90b6948a3f5072e8ac7e9732b25c2612ac93bf25e40527dec80f7fbb65e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.neuint.2017.12.001$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29224965$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Antonyan, Alvard</creatorcontrib><creatorcontrib>Schlenzig, Dagmar</creatorcontrib><creatorcontrib>Schilling, Stephan</creatorcontrib><creatorcontrib>Naumann, Marcel</creatorcontrib><creatorcontrib>Sharoyan, Svetlana</creatorcontrib><creatorcontrib>Mardanyan, Sona</creatorcontrib><creatorcontrib>Demuth, Hans-Ulrich</creatorcontrib><title>Concerted action of dipeptidyl peptidase IV and glutaminyl cyclase results in formation of pyroglutamate-modified amyloid peptides in vitro</title><title>Neurochemistry international</title><addtitle>Neurochem Int</addtitle><description>Compelling evidence suggests a crucial role of amyloid beta peptides (Aβ(1-40/42)) in the etiology of Alzheimer's disease (AD). The N-terminal truncation of Aβ(1-40/42) and their modification, e.g. by glutaminyl cyclase (QC), is expected to enhance the amyloid toxicity. In this work, the MALDI-TOF mass spectrometry application proved N-terminal cleavage of Aβ(1-40/42) by purified dipeptidyl peptidase IV (DPPIV) in vitro observed earlier. The subsequent transformation of resulted Aβ(3-40/42) to pE-Aβ(3-40/42) in QC catalyzed glutamate cyclization was manifested. Hence, consecutive conversion of Aβ(1-40/42) by DPPIV and QC can be assumed as a potential mechanism of formation of non-degrading pyroglutamated pE-Aβ(3-40/42), which might accumulate and contribute to AD progression. The in vitro acceleration of Aβ(1-40) aggregation in the simultaneous presence of DPPIV and QC was shown also.
•MALDI-TOF analysis proved N-terminal dipeptide cleavage from Aβ(1-40/42) by DPPIV.•Action of DPPIV is followed by QC catalyzed transformation to pE-Aβ(3-40/42) in vitro.•The aggregation of Aβ(1-40/42) is hindered by DPPIV and accelerated by QC in vitro.</description><subject>Amino Acid Sequence</subject><subject>Aminoacyltransferases - metabolism</subject><subject>Amyloid beta peptides</subject><subject>Amyloid beta-Peptides - analysis</subject><subject>Amyloid beta-Peptides - genetics</subject><subject>Amyloid beta-Peptides - metabolism</subject><subject>Animals</subject><subject>Cattle</subject><subject>Dipeptidyl Peptidase 4 - metabolism</subject><subject>Dipeptidyl peptidase IV</subject><subject>Enzyme-substrate interactions</subject><subject>Glutaminyl cyclase</subject><subject>Humans</subject><subject>MALDI-TOF mass spectrometry</subject><subject>Peptide Fragments - analysis</subject><subject>Peptide Fragments - genetics</subject><subject>Peptide Fragments - metabolism</subject><subject>Protein Aggregates - drug effects</subject><subject>Protein Aggregates - physiology</subject><subject>Pyrrolidonecarboxylic Acid - pharmacology</subject><subject>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods</subject><issn>0197-0186</issn><issn>1872-9754</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1q3TAQx0VpaF7S3qAULbuxK8mWZW0K5ZG2gUA2abdClkZFD9tyJTngO_QQPUtOVhu_ZNmVBPP_YOaH0HtKSkpo8-lUjjD7MZeMUFFSVhJCX6EDbQUrpOD1a3QgVIqC0La5RFcpnQghQhL-Bl0yyVgtG35Af45hNBAzWKxN9mHEwWHrJ5iyt0uP949OgG9_Yj1a_Kufsx78uM7MYvptEiHNfU7Yj9iFOOjnmGmJYZfrDMUQrHd-6xmWPnh7jobN9_T30ecY3qILp_sE787vNfrx9ebh-L24u_92e_xyV5iqYblonaFOkq6Rdasrx4lg0GojQIqKdYwb1lCmjaw6xzjUhDNhwbTECdd1DYfqGn3cc6cYfs-Qshp8MtD3eoQwJ7WejXNZVy1ZpfUuNTGkFMGpKfpBx0VRojYO6qR2DmrjoChTK4fV9uHcMHcD2BfT8-FXweddAOuejx6iSsbDisL6CCYrG_z_G_4B53agGw</recordid><startdate>201802</startdate><enddate>201802</enddate><creator>Antonyan, Alvard</creator><creator>Schlenzig, Dagmar</creator><creator>Schilling, Stephan</creator><creator>Naumann, Marcel</creator><creator>Sharoyan, Svetlana</creator><creator>Mardanyan, Sona</creator><creator>Demuth, Hans-Ulrich</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201802</creationdate><title>Concerted action of dipeptidyl peptidase IV and glutaminyl cyclase results in formation of pyroglutamate-modified amyloid peptides in vitro</title><author>Antonyan, Alvard ; Schlenzig, Dagmar ; Schilling, Stephan ; Naumann, Marcel ; Sharoyan, Svetlana ; Mardanyan, Sona ; Demuth, Hans-Ulrich</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-8fc1f90b6948a3f5072e8ac7e9732b25c2612ac93bf25e40527dec80f7fbb65e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Amino Acid Sequence</topic><topic>Aminoacyltransferases - metabolism</topic><topic>Amyloid beta peptides</topic><topic>Amyloid beta-Peptides - analysis</topic><topic>Amyloid beta-Peptides - genetics</topic><topic>Amyloid beta-Peptides - metabolism</topic><topic>Animals</topic><topic>Cattle</topic><topic>Dipeptidyl Peptidase 4 - metabolism</topic><topic>Dipeptidyl peptidase IV</topic><topic>Enzyme-substrate interactions</topic><topic>Glutaminyl cyclase</topic><topic>Humans</topic><topic>MALDI-TOF mass spectrometry</topic><topic>Peptide Fragments - analysis</topic><topic>Peptide Fragments - genetics</topic><topic>Peptide Fragments - metabolism</topic><topic>Protein Aggregates - drug effects</topic><topic>Protein Aggregates - physiology</topic><topic>Pyrrolidonecarboxylic Acid - pharmacology</topic><topic>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Antonyan, Alvard</creatorcontrib><creatorcontrib>Schlenzig, Dagmar</creatorcontrib><creatorcontrib>Schilling, Stephan</creatorcontrib><creatorcontrib>Naumann, Marcel</creatorcontrib><creatorcontrib>Sharoyan, Svetlana</creatorcontrib><creatorcontrib>Mardanyan, Sona</creatorcontrib><creatorcontrib>Demuth, Hans-Ulrich</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Neurochemistry international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Antonyan, Alvard</au><au>Schlenzig, Dagmar</au><au>Schilling, Stephan</au><au>Naumann, Marcel</au><au>Sharoyan, Svetlana</au><au>Mardanyan, Sona</au><au>Demuth, Hans-Ulrich</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Concerted action of dipeptidyl peptidase IV and glutaminyl cyclase results in formation of pyroglutamate-modified amyloid peptides in vitro</atitle><jtitle>Neurochemistry international</jtitle><addtitle>Neurochem Int</addtitle><date>2018-02</date><risdate>2018</risdate><volume>113</volume><spage>112</spage><epage>119</epage><pages>112-119</pages><issn>0197-0186</issn><eissn>1872-9754</eissn><abstract>Compelling evidence suggests a crucial role of amyloid beta peptides (Aβ(1-40/42)) in the etiology of Alzheimer's disease (AD). The N-terminal truncation of Aβ(1-40/42) and their modification, e.g. by glutaminyl cyclase (QC), is expected to enhance the amyloid toxicity. In this work, the MALDI-TOF mass spectrometry application proved N-terminal cleavage of Aβ(1-40/42) by purified dipeptidyl peptidase IV (DPPIV) in vitro observed earlier. The subsequent transformation of resulted Aβ(3-40/42) to pE-Aβ(3-40/42) in QC catalyzed glutamate cyclization was manifested. Hence, consecutive conversion of Aβ(1-40/42) by DPPIV and QC can be assumed as a potential mechanism of formation of non-degrading pyroglutamated pE-Aβ(3-40/42), which might accumulate and contribute to AD progression. The in vitro acceleration of Aβ(1-40) aggregation in the simultaneous presence of DPPIV and QC was shown also.
•MALDI-TOF analysis proved N-terminal dipeptide cleavage from Aβ(1-40/42) by DPPIV.•Action of DPPIV is followed by QC catalyzed transformation to pE-Aβ(3-40/42) in vitro.•The aggregation of Aβ(1-40/42) is hindered by DPPIV and accelerated by QC in vitro.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>29224965</pmid><doi>10.1016/j.neuint.2017.12.001</doi><tpages>8</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0197-0186 |
ispartof | Neurochemistry international, 2018-02, Vol.113, p.112-119 |
issn | 0197-0186 1872-9754 |
language | eng |
recordid | cdi_proquest_miscellaneous_1975594380 |
source | MEDLINE; Access via ScienceDirect (Elsevier) |
subjects | Amino Acid Sequence Aminoacyltransferases - metabolism Amyloid beta peptides Amyloid beta-Peptides - analysis Amyloid beta-Peptides - genetics Amyloid beta-Peptides - metabolism Animals Cattle Dipeptidyl Peptidase 4 - metabolism Dipeptidyl peptidase IV Enzyme-substrate interactions Glutaminyl cyclase Humans MALDI-TOF mass spectrometry Peptide Fragments - analysis Peptide Fragments - genetics Peptide Fragments - metabolism Protein Aggregates - drug effects Protein Aggregates - physiology Pyrrolidonecarboxylic Acid - pharmacology Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods |
title | Concerted action of dipeptidyl peptidase IV and glutaminyl cyclase results in formation of pyroglutamate-modified amyloid peptides in vitro |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-13T17%3A17%3A25IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Concerted%20action%20of%20dipeptidyl%20peptidase%20IV%20and%20glutaminyl%20cyclase%20results%20in%20formation%20of%20pyroglutamate-modified%20amyloid%20peptides%20in%C2%A0vitro&rft.jtitle=Neurochemistry%20international&rft.au=Antonyan,%20Alvard&rft.date=2018-02&rft.volume=113&rft.spage=112&rft.epage=119&rft.pages=112-119&rft.issn=0197-0186&rft.eissn=1872-9754&rft_id=info:doi/10.1016/j.neuint.2017.12.001&rft_dat=%3Cproquest_cross%3E1975594380%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1975594380&rft_id=info:pmid/29224965&rft_els_id=S019701861730462X&rfr_iscdi=true |