Pore Formation by the Cytotoxic Islet Amyloid Peptide Amylin
Amylin is a 37-amino acid cytotoxic constituent of amyloid deposits found in the islets of Langerhans of patients with type II diabetes. Extracellular accumulation of this peptide results in damage to insulin-producing β cell membranes and cell death. We report here that at cytotoxic concentrations...
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| Veröffentlicht in: | The Journal of biological chemistry 1996-01, Vol.271 (4), p.1988-1992 |
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| Format: | Artikel |
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| container_end_page | 1992 |
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| container_issue | 4 |
| container_start_page | 1988 |
| container_title | The Journal of biological chemistry |
| container_volume | 271 |
| creator | Mirzabekov, T A Lin, M C Kagan, B L |
| description | Amylin is a 37-amino acid cytotoxic constituent of amyloid deposits found in the islets of Langerhans of patients with type
II diabetes. Extracellular accumulation of this peptide results in damage to insulin-producing β cell membranes and cell death.
We report here that at cytotoxic concentrations, amylin forms voltage-dependent, relatively nonselective, ion-permeable channels
in planar phospholipid bilayer membranes. Channel formation is dependent upon lipid membrane composition, ionic strength,
and membrane potential. At 1-10 μM, cytotoxic human amylin dramatically increases the conductance of lipid bilayer membranes,
while noncytotoxic rat amylin does not. We suggest that channel formation may be the mechanism of cytotoxicity of human amylin. |
| doi_str_mv | 10.1074/jbc.271.4.1988 |
| format | Article |
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II diabetes. Extracellular accumulation of this peptide results in damage to insulin-producing β cell membranes and cell death.
We report here that at cytotoxic concentrations, amylin forms voltage-dependent, relatively nonselective, ion-permeable channels
in planar phospholipid bilayer membranes. Channel formation is dependent upon lipid membrane composition, ionic strength,
and membrane potential. At 1-10 μM, cytotoxic human amylin dramatically increases the conductance of lipid bilayer membranes,
while noncytotoxic rat amylin does not. We suggest that channel formation may be the mechanism of cytotoxicity of human amylin.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.271.4.1988</identifier><identifier>PMID: 8567648</identifier><language>eng</language><publisher>United States: American Society for Biochemistry and Molecular Biology</publisher><subject>Amyloid - chemistry ; Animals ; Cell Membrane Permeability ; Cytotoxins - chemistry ; Electric Conductivity ; Humans ; Ion Channels - chemistry ; Islet Amyloid Polypeptide ; Lipid Bilayers ; Membrane Proteins - chemistry ; Rats</subject><ispartof>The Journal of biological chemistry, 1996-01, Vol.271 (4), p.1988-1992</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c454t-c0e34a376c7d65d812e89509dd257f686f97ba3b2950792bf8763af01979c0a3</citedby><cites>FETCH-LOGICAL-c454t-c0e34a376c7d65d812e89509dd257f686f97ba3b2950792bf8763af01979c0a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8567648$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mirzabekov, T A</creatorcontrib><creatorcontrib>Lin, M C</creatorcontrib><creatorcontrib>Kagan, B L</creatorcontrib><title>Pore Formation by the Cytotoxic Islet Amyloid Peptide Amylin</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Amylin is a 37-amino acid cytotoxic constituent of amyloid deposits found in the islets of Langerhans of patients with type
II diabetes. Extracellular accumulation of this peptide results in damage to insulin-producing β cell membranes and cell death.
We report here that at cytotoxic concentrations, amylin forms voltage-dependent, relatively nonselective, ion-permeable channels
in planar phospholipid bilayer membranes. Channel formation is dependent upon lipid membrane composition, ionic strength,
and membrane potential. At 1-10 μM, cytotoxic human amylin dramatically increases the conductance of lipid bilayer membranes,
while noncytotoxic rat amylin does not. We suggest that channel formation may be the mechanism of cytotoxicity of human amylin.</description><subject>Amyloid - chemistry</subject><subject>Animals</subject><subject>Cell Membrane Permeability</subject><subject>Cytotoxins - chemistry</subject><subject>Electric Conductivity</subject><subject>Humans</subject><subject>Ion Channels - chemistry</subject><subject>Islet Amyloid Polypeptide</subject><subject>Lipid Bilayers</subject><subject>Membrane Proteins - chemistry</subject><subject>Rats</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkDFPwzAQhS0EKqWwsiFFDGwJdmzHtsRSVRQqVaJDBzbLcRziKqmL7Qry70lphbjldO-9e8MHwC2CGYKMPG5KneUMZSRDgvMzMEaQ4xRT9H4OxhDmKBU55ZfgKoQNHIYINAIjTgtWED4GTyvnTTJ3vlPRum1S9klsTDLro4vu2-pkEVoTk2nXt85Wycrsoq3M72231-CiVm0wN6c9Aev583r2mi7fXhaz6TLVhJKYamgwUZgVmlUFrTjKDRcUiqrKKasLXtSClQqX-SAykZc1ZwVWNUSCCQ0VnoCHY-3Ou8-9CVF2NmjTtmpr3D5IxCAWmOIhmB2D2rsQvKnlzttO-V4iKA-05EBLDrQkkQdaw8PdqXlfdqb6i5_wDP790W_sR_NlvZGldbox3f-SH9aKb7M</recordid><startdate>19960126</startdate><enddate>19960126</enddate><creator>Mirzabekov, T A</creator><creator>Lin, M C</creator><creator>Kagan, B L</creator><general>American Society for Biochemistry and Molecular Biology</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>7TK</scope></search><sort><creationdate>19960126</creationdate><title>Pore Formation by the Cytotoxic Islet Amyloid Peptide Amylin</title><author>Mirzabekov, T A ; Lin, M C ; Kagan, B L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c454t-c0e34a376c7d65d812e89509dd257f686f97ba3b2950792bf8763af01979c0a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Amyloid - chemistry</topic><topic>Animals</topic><topic>Cell Membrane Permeability</topic><topic>Cytotoxins - chemistry</topic><topic>Electric Conductivity</topic><topic>Humans</topic><topic>Ion Channels - chemistry</topic><topic>Islet Amyloid Polypeptide</topic><topic>Lipid Bilayers</topic><topic>Membrane Proteins - chemistry</topic><topic>Rats</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mirzabekov, T A</creatorcontrib><creatorcontrib>Lin, M C</creatorcontrib><creatorcontrib>Kagan, B L</creatorcontrib><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><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mirzabekov, T A</au><au>Lin, M C</au><au>Kagan, B L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pore Formation by the Cytotoxic Islet Amyloid Peptide Amylin</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1996-01-26</date><risdate>1996</risdate><volume>271</volume><issue>4</issue><spage>1988</spage><epage>1992</epage><pages>1988-1992</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Amylin is a 37-amino acid cytotoxic constituent of amyloid deposits found in the islets of Langerhans of patients with type
II diabetes. Extracellular accumulation of this peptide results in damage to insulin-producing β cell membranes and cell death.
We report here that at cytotoxic concentrations, amylin forms voltage-dependent, relatively nonselective, ion-permeable channels
in planar phospholipid bilayer membranes. Channel formation is dependent upon lipid membrane composition, ionic strength,
and membrane potential. At 1-10 μM, cytotoxic human amylin dramatically increases the conductance of lipid bilayer membranes,
while noncytotoxic rat amylin does not. We suggest that channel formation may be the mechanism of cytotoxicity of human amylin.</abstract><cop>United States</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>8567648</pmid><doi>10.1074/jbc.271.4.1988</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-9258 |
| ispartof | The Journal of biological chemistry, 1996-01, Vol.271 (4), p.1988-1992 |
| issn | 0021-9258 1083-351X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_17039353 |
| source | MEDLINE; Alma/SFX Local Collection; EZB Electronic Journals Library |
| subjects | Amyloid - chemistry Animals Cell Membrane Permeability Cytotoxins - chemistry Electric Conductivity Humans Ion Channels - chemistry Islet Amyloid Polypeptide Lipid Bilayers Membrane Proteins - chemistry Rats |
| title | Pore Formation by the Cytotoxic Islet Amyloid Peptide Amylin |
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