Reversibility of Scrapie Inactivation Is Enhanced by Copper
The only known difference between the cellular (PrPC) and scrapie-specific (PrPSc) isoforms of the prion protein is conformational. Because disruption of PrPSc structure decreases scrapie infectivity, restoration of the disease-specific conformation should restore infectivity. In this study, disrupt...
Gespeichert in:
| Veröffentlicht in: | The Journal of biological chemistry 1998-10, Vol.273 (40), p.25545-25547 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 25547 |
|---|---|
| container_issue | 40 |
| container_start_page | 25545 |
| container_title | The Journal of biological chemistry |
| container_volume | 273 |
| creator | McKenzie, Debbie Bartz, Jason Mirwald, Jean Olander, Doris Marsh, Richard Aiken, Judd |
| description | The only known difference between the cellular (PrPC) and scrapie-specific (PrPSc) isoforms of the prion protein is conformational. Because disruption of PrPSc structure decreases scrapie infectivity, restoration of the disease-specific conformation should restore infectivity. In this study, disruption of PrPSc (as monitored by the loss of proteinase K resistance) by guanidine hydrochloride (GdnHCl) resulted in decreased infectivity. Upon dilution of the GdnHCl, protease resistance of PrP was restored and infectivity was regained. The addition of copper facilitated restoration of both infectivity and protease resistance of PrP in a subset of samples that did not renature by the simple dilution of the GdnHCl. These data demonstrate that loss of scrapie infectivity can be a reversible process and that copper can enhance this restoration of proteinase K resistance and infectivity. |
| doi_str_mv | 10.1074/jbc.273.40.25545 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_73932659</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0021925819598532</els_id><sourcerecordid>73932659</sourcerecordid><originalsourceid>FETCH-LOGICAL-c535t-8a8ea21af62d51f237b5f20899a96e1bfe321c88af081df0790282ad02a86d663</originalsourceid><addsrcrecordid>eNqFkE1rGzEQhkVpSJ20914Keyi9rTOSVrtSeyomH4ZAIG6gN6HVjmIFe7WV1g7-95Frk1vIXObwvvMwPIR8pTCl0FQXT62dsoZPK5gyISrxgUwoSF5yQf9-JBMARkvFhPxEzlJ6gjyVoqfkVDWVZFRMyK973GJMvvUrP-6K4IqFjWbwWMx7Y0e_NaMPfTFPxWW_NL3Frmh3xSwMA8bP5MSZVcIvx31OHq4u_8xuytu76_ns921pBRdjKY1Ew6hxNesEdYw3rXAMpFJG1Uhbh5xRK6VxIGnnoFHAJDMdMCPrrq75Oflx4A4x_NtgGvXaJ4urlekxbJJuuOKsFurdIm1AcUVlLsKhaGNIKaLTQ_RrE3eagt6L1VmszmJ1Bfq_2Hzy7cjetGvsXg-OJnP-_ZAv_ePy2UfUrQ92ies3MM4EbR6jT_phQZVqQFZc8pz_POSYhW49Rp2sx733jLSj7oJ_-8cXNw6alA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17093918</pqid></control><display><type>article</type><title>Reversibility of Scrapie Inactivation Is Enhanced by Copper</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>McKenzie, Debbie ; Bartz, Jason ; Mirwald, Jean ; Olander, Doris ; Marsh, Richard ; Aiken, Judd</creator><creatorcontrib>McKenzie, Debbie ; Bartz, Jason ; Mirwald, Jean ; Olander, Doris ; Marsh, Richard ; Aiken, Judd</creatorcontrib><description>The only known difference between the cellular (PrPC) and scrapie-specific (PrPSc) isoforms of the prion protein is conformational. Because disruption of PrPSc structure decreases scrapie infectivity, restoration of the disease-specific conformation should restore infectivity. In this study, disruption of PrPSc (as monitored by the loss of proteinase K resistance) by guanidine hydrochloride (GdnHCl) resulted in decreased infectivity. Upon dilution of the GdnHCl, protease resistance of PrP was restored and infectivity was regained. The addition of copper facilitated restoration of both infectivity and protease resistance of PrP in a subset of samples that did not renature by the simple dilution of the GdnHCl. These data demonstrate that loss of scrapie infectivity can be a reversible process and that copper can enhance this restoration of proteinase K resistance and infectivity.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.273.40.25545</identifier><identifier>PMID: 9748215</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Brain - pathology ; COPPER ; Copper - pharmacology ; COPPER SULPHATE ; Cricetinae ; Endopeptidase K - metabolism ; Guanidine - pharmacology ; GUANIDINE HYDROCHLORIDE ; GUANIDINES ; HAMSTERS ; INFECTIVITY ; Mesocricetus ; MOLECULAR CONFORMATION ; PATHOGENICITY ; Prion Diseases - physiopathology ; PRION PROTEINS ; PRIONS ; PROTEASES ; Protein Conformation ; Protein Denaturation - drug effects ; PrPC Proteins - chemistry ; PrPSc Proteins - chemistry ; RESISTANCE ; SCRAPIE ; Scrapie - physiopathology</subject><ispartof>The Journal of biological chemistry, 1998-10, Vol.273 (40), p.25545-25547</ispartof><rights>1998 © 1998 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c535t-8a8ea21af62d51f237b5f20899a96e1bfe321c88af081df0790282ad02a86d663</citedby><cites>FETCH-LOGICAL-c535t-8a8ea21af62d51f237b5f20899a96e1bfe321c88af081df0790282ad02a86d663</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,27933,27934</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9748215$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>McKenzie, Debbie</creatorcontrib><creatorcontrib>Bartz, Jason</creatorcontrib><creatorcontrib>Mirwald, Jean</creatorcontrib><creatorcontrib>Olander, Doris</creatorcontrib><creatorcontrib>Marsh, Richard</creatorcontrib><creatorcontrib>Aiken, Judd</creatorcontrib><title>Reversibility of Scrapie Inactivation Is Enhanced by Copper</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>The only known difference between the cellular (PrPC) and scrapie-specific (PrPSc) isoforms of the prion protein is conformational. Because disruption of PrPSc structure decreases scrapie infectivity, restoration of the disease-specific conformation should restore infectivity. In this study, disruption of PrPSc (as monitored by the loss of proteinase K resistance) by guanidine hydrochloride (GdnHCl) resulted in decreased infectivity. Upon dilution of the GdnHCl, protease resistance of PrP was restored and infectivity was regained. The addition of copper facilitated restoration of both infectivity and protease resistance of PrP in a subset of samples that did not renature by the simple dilution of the GdnHCl. These data demonstrate that loss of scrapie infectivity can be a reversible process and that copper can enhance this restoration of proteinase K resistance and infectivity.</description><subject>Animals</subject><subject>Brain - pathology</subject><subject>COPPER</subject><subject>Copper - pharmacology</subject><subject>COPPER SULPHATE</subject><subject>Cricetinae</subject><subject>Endopeptidase K - metabolism</subject><subject>Guanidine - pharmacology</subject><subject>GUANIDINE HYDROCHLORIDE</subject><subject>GUANIDINES</subject><subject>HAMSTERS</subject><subject>INFECTIVITY</subject><subject>Mesocricetus</subject><subject>MOLECULAR CONFORMATION</subject><subject>PATHOGENICITY</subject><subject>Prion Diseases - physiopathology</subject><subject>PRION PROTEINS</subject><subject>PRIONS</subject><subject>PROTEASES</subject><subject>Protein Conformation</subject><subject>Protein Denaturation - drug effects</subject><subject>PrPC Proteins - chemistry</subject><subject>PrPSc Proteins - chemistry</subject><subject>RESISTANCE</subject><subject>SCRAPIE</subject><subject>Scrapie - physiopathology</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1rGzEQhkVpSJ20914Keyi9rTOSVrtSeyomH4ZAIG6gN6HVjmIFe7WV1g7-95Frk1vIXObwvvMwPIR8pTCl0FQXT62dsoZPK5gyISrxgUwoSF5yQf9-JBMARkvFhPxEzlJ6gjyVoqfkVDWVZFRMyK973GJMvvUrP-6K4IqFjWbwWMx7Y0e_NaMPfTFPxWW_NL3Frmh3xSwMA8bP5MSZVcIvx31OHq4u_8xuytu76_ns921pBRdjKY1Ew6hxNesEdYw3rXAMpFJG1Uhbh5xRK6VxIGnnoFHAJDMdMCPrrq75Oflx4A4x_NtgGvXaJ4urlekxbJJuuOKsFurdIm1AcUVlLsKhaGNIKaLTQ_RrE3eagt6L1VmszmJ1Bfq_2Hzy7cjetGvsXg-OJnP-_ZAv_ePy2UfUrQ92ies3MM4EbR6jT_phQZVqQFZc8pz_POSYhW49Rp2sx733jLSj7oJ_-8cXNw6alA</recordid><startdate>19981002</startdate><enddate>19981002</enddate><creator>McKenzie, Debbie</creator><creator>Bartz, Jason</creator><creator>Mirwald, Jean</creator><creator>Olander, Doris</creator><creator>Marsh, Richard</creator><creator>Aiken, Judd</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</scope><scope>FBQ</scope><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>7TK</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>19981002</creationdate><title>Reversibility of Scrapie Inactivation Is Enhanced by Copper</title><author>McKenzie, Debbie ; Bartz, Jason ; Mirwald, Jean ; Olander, Doris ; Marsh, Richard ; Aiken, Judd</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c535t-8a8ea21af62d51f237b5f20899a96e1bfe321c88af081df0790282ad02a86d663</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Animals</topic><topic>Brain - pathology</topic><topic>COPPER</topic><topic>Copper - pharmacology</topic><topic>COPPER SULPHATE</topic><topic>Cricetinae</topic><topic>Endopeptidase K - metabolism</topic><topic>Guanidine - pharmacology</topic><topic>GUANIDINE HYDROCHLORIDE</topic><topic>GUANIDINES</topic><topic>HAMSTERS</topic><topic>INFECTIVITY</topic><topic>Mesocricetus</topic><topic>MOLECULAR CONFORMATION</topic><topic>PATHOGENICITY</topic><topic>Prion Diseases - physiopathology</topic><topic>PRION PROTEINS</topic><topic>PRIONS</topic><topic>PROTEASES</topic><topic>Protein Conformation</topic><topic>Protein Denaturation - drug effects</topic><topic>PrPC Proteins - chemistry</topic><topic>PrPSc Proteins - chemistry</topic><topic>RESISTANCE</topic><topic>SCRAPIE</topic><topic>Scrapie - physiopathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>McKenzie, Debbie</creatorcontrib><creatorcontrib>Bartz, Jason</creatorcontrib><creatorcontrib>Mirwald, Jean</creatorcontrib><creatorcontrib>Olander, Doris</creatorcontrib><creatorcontrib>Marsh, Richard</creatorcontrib><creatorcontrib>Aiken, Judd</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>McKenzie, Debbie</au><au>Bartz, Jason</au><au>Mirwald, Jean</au><au>Olander, Doris</au><au>Marsh, Richard</au><au>Aiken, Judd</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reversibility of Scrapie Inactivation Is Enhanced by Copper</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1998-10-02</date><risdate>1998</risdate><volume>273</volume><issue>40</issue><spage>25545</spage><epage>25547</epage><pages>25545-25547</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>The only known difference between the cellular (PrPC) and scrapie-specific (PrPSc) isoforms of the prion protein is conformational. Because disruption of PrPSc structure decreases scrapie infectivity, restoration of the disease-specific conformation should restore infectivity. In this study, disruption of PrPSc (as monitored by the loss of proteinase K resistance) by guanidine hydrochloride (GdnHCl) resulted in decreased infectivity. Upon dilution of the GdnHCl, protease resistance of PrP was restored and infectivity was regained. The addition of copper facilitated restoration of both infectivity and protease resistance of PrP in a subset of samples that did not renature by the simple dilution of the GdnHCl. These data demonstrate that loss of scrapie infectivity can be a reversible process and that copper can enhance this restoration of proteinase K resistance and infectivity.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>9748215</pmid><doi>10.1074/jbc.273.40.25545</doi><tpages>3</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-9258 |
| ispartof | The Journal of biological chemistry, 1998-10, Vol.273 (40), p.25545-25547 |
| issn | 0021-9258 1083-351X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_73932659 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals Brain - pathology COPPER Copper - pharmacology COPPER SULPHATE Cricetinae Endopeptidase K - metabolism Guanidine - pharmacology GUANIDINE HYDROCHLORIDE GUANIDINES HAMSTERS INFECTIVITY Mesocricetus MOLECULAR CONFORMATION PATHOGENICITY Prion Diseases - physiopathology PRION PROTEINS PRIONS PROTEASES Protein Conformation Protein Denaturation - drug effects PrPC Proteins - chemistry PrPSc Proteins - chemistry RESISTANCE SCRAPIE Scrapie - physiopathology |
| title | Reversibility of Scrapie Inactivation Is Enhanced by Copper |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-11-29T01%3A44%3A56IST&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=Reversibility%20of%20Scrapie%20Inactivation%20Is%20Enhanced%20by%20Copper&rft.jtitle=The%20Journal%20of%20biological%20chemistry&rft.au=McKenzie,%20Debbie&rft.date=1998-10-02&rft.volume=273&rft.issue=40&rft.spage=25545&rft.epage=25547&rft.pages=25545-25547&rft.issn=0021-9258&rft.eissn=1083-351X&rft_id=info:doi/10.1074/jbc.273.40.25545&rft_dat=%3Cproquest_cross%3E73932659%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=17093918&rft_id=info:pmid/9748215&rft_els_id=S0021925819598532&rfr_iscdi=true |