DC Field | Value | Language |
---|---|---|
dc.contributor.author | Azzam, Sarah Kassem | ko |
dc.contributor.author | Jang, Hyunwoo | ko |
dc.contributor.author | Choi, Myung Chul | ko |
dc.contributor.author | Alsafari, Habiba | ko |
dc.contributor.author | Lukman, Suryani | ko |
dc.contributor.author | Lee, Sungmun | ko |
dc.date.accessioned | 2018-07-24T01:37:56Z | - |
dc.date.available | 2018-07-24T01:37:56Z | - |
dc.date.created | 2018-06-25 | - |
dc.date.created | 2018-06-25 | - |
dc.date.issued | 2018-06 | - |
dc.identifier.citation | MOLECULAR PHARMACEUTICS, v.15, no.6, pp.2098 - 2106 | - |
dc.identifier.issn | 1543-8384 | - |
dc.identifier.uri | http://hdl.handle.net/10203/243696 | - |
dc.description.abstract | More than 30 human degenerative diseases result from protein aggregation such as Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM). Islet amyloid deposits, a hallmark in T2DM, are found in pancreatic islets of more than 90% of T2DM patients. An association between amylin aggregation and reduction in beta-cell mass was also established by post-mortem studies. A strategy in preventing protein aggregation-related disorders is to inhibit the protein aggregation and associated toxicity. In this study, we demonstrated that two inhibitors, lipoic acid and ascorbic acid, significantly inhibited amylin aggregation. Compared to amylin (15 mu M) as 100%, lipoic acid and ascorbic acid reduced amylin fibril formation to 42.1 +/- 17.2% and 42.9 +/- 12.8%, respectively, which is confirmed by fluorescence and TEM images. In cell viability tests, both inhibitors protected RIN-m5f beta-cells from the toxicity of amylin aggregates. At 10:1 molar ratio of lipoic acid to amylin, lipoic acid with amylin increased the cell viability to 70.3%, whereas only 42.8% RIN-m5f beta-cells survived in amylin aggregates. For ascorbic acid, an equimolar ratio achieved the highest cell viability of 63.3% as compared to 42.8% with amylin aggregates only. Docking results showed that lipoic acid and ascorbic acid physically interact with amylin amyloidogenic region (residues Ser20-Ser29) via hydrophobic interactions; hence reducing aggregation levels. Therefore, lipoic acid and ascorbic acid prevented amylin aggregation via hydrophobic interactions, which resulted in the prevention of cell toxicity in vitro. | - |
dc.language | English | - |
dc.publisher | AMER CHEMICAL SOC | - |
dc.subject | ISLET AMYLOID POLYPEPTIDE | - |
dc.subject | TYPE-2 DIABETES-MELLITUS | - |
dc.subject | PROTEIN AGGREGATION | - |
dc.subject | S20G MUTATION | - |
dc.subject | GENE S20G | - |
dc.subject | DISEASES | - |
dc.subject | JAPANESE | - |
dc.subject | FIBRILS | - |
dc.subject | PEPTIDE | - |
dc.subject | PH | - |
dc.title | Inhibition of Human Amylin Aggregation and Cellular Toxicity by Lipoic Acid and Ascorbic Acid | - |
dc.type | Article | - |
dc.identifier.wosid | 000434491800003 | - |
dc.identifier.scopusid | 2-s2.0-85046554337 | - |
dc.type.rims | ART | - |
dc.citation.volume | 15 | - |
dc.citation.issue | 6 | - |
dc.citation.beginningpage | 2098 | - |
dc.citation.endingpage | 2106 | - |
dc.citation.publicationname | MOLECULAR PHARMACEUTICS | - |
dc.identifier.doi | 10.1021/acs.molpharmaceut.7b01009 | - |
dc.contributor.localauthor | Choi, Myung Chul | - |
dc.contributor.nonIdAuthor | Azzam, Sarah Kassem | - |
dc.contributor.nonIdAuthor | Jang, Hyunwoo | - |
dc.contributor.nonIdAuthor | Alsafari, Habiba | - |
dc.contributor.nonIdAuthor | Lukman, Suryani | - |
dc.contributor.nonIdAuthor | Lee, Sungmun | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | amyloid inhibition | - |
dc.subject.keywordAuthor | amylin | - |
dc.subject.keywordAuthor | type 2 diabetes | - |
dc.subject.keywordAuthor | ascorbic acid | - |
dc.subject.keywordAuthor | lipoic acid | - |
dc.subject.keywordPlus | ISLET AMYLOID POLYPEPTIDE | - |
dc.subject.keywordPlus | TYPE-2 DIABETES-MELLITUS | - |
dc.subject.keywordPlus | PROTEIN AGGREGATION | - |
dc.subject.keywordPlus | S20G MUTATION | - |
dc.subject.keywordPlus | GENE S20G | - |
dc.subject.keywordPlus | DISEASES | - |
dc.subject.keywordPlus | JAPANESE | - |
dc.subject.keywordPlus | FIBRILS | - |
dc.subject.keywordPlus | PEPTIDE | - |
dc.subject.keywordPlus | PH | - |
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