High glucose upregulates BACE1-mediated A beta production through ROS-dependent HIF-1 alpha and LXR alpha/ABCA1-regulated lipid raft reorganization in SK-N-MC cells
DC Field | Value | Language |
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dc.contributor.author | Lee, Hyun Jik | - |
dc.contributor.author | Ryu, Jung Min | - |
dc.contributor.author | Jung, Young Hyun | - |
dc.contributor.author | Lee, Sei-Jung | - |
dc.contributor.author | Kim, Jeong Yeon | - |
dc.contributor.author | Lee, Sang Hun | - |
dc.contributor.author | Hwang, In Koo | - |
dc.contributor.author | Seong, Je Kyung | - |
dc.contributor.author | Han, Ho Jae | - |
dc.date.accessioned | 2021-08-11T16:44:30Z | - |
dc.date.available | 2021-08-11T16:44:30Z | - |
dc.date.issued | 2016-11-10 | - |
dc.identifier.issn | 2045-2322 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/8601 | - |
dc.description.abstract | There is an accumulation of evidence indicating that the risk of Alzheimer's disease is associated with diabetes mellitus, an indicator of high glucose concentrations in blood plasma. This study investigated the effect of high glucose on BACE1 expression and amyloidogenesis in vivo, and we present details of the mechanism associated with those effects. Our results, using ZLC and ZDF rat models, showed that ZDF rats have high levels of amyloid-beta (A beta), phosphorylated tau, BACE1, and APP-C99. In vitro result with mouse hippocampal neuron and SK-N-MC, high glucose stimulated A beta secretion and apoptosis in a dose-dependent manner. In addition, high glucose increased BACE1 and APP-C99 expressions, which were reversed by a reactive oxygen species (ROS) scavenger. Indeed, high glucose increased intracellular ROS levels and HIF-1 alpha expression, associated with regulation of BACE1 and Liver X Receptor alpha (LXR alpha). In addition, high glucose induced ATP-binding cassette transporter A1 (ABCA1) down-regulation, was associated with LXR-induced lipid raft reorganization and BACE1 localization on the lipid raft. Furthermore, silencing of BACE1 expression was shown to regulate A beta secretion and apoptosis of SK-N-MC. In conclusion, high glucose upregulates BACE1 expression and activity through HIF-1 alpha and LXR alpha/ABCA1-regulated lipid raft reorganization, leading to A beta production and apoptosis of SK-N-MC. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | Nature Publishing Group | - |
dc.title | High glucose upregulates BACE1-mediated A beta production through ROS-dependent HIF-1 alpha and LXR alpha/ABCA1-regulated lipid raft reorganization in SK-N-MC cells | - |
dc.type | Article | - |
dc.publisher.location | 영국 | - |
dc.identifier.doi | 10.1038/srep36746 | - |
dc.identifier.scopusid | 2-s2.0-84995519769 | - |
dc.identifier.wosid | 000388087200001 | - |
dc.identifier.bibliographicCitation | Scientific Reports, v.6 | - |
dc.citation.title | Scientific Reports | - |
dc.citation.volume | 6 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordPlus | NICOTINIC ACETYLCHOLINE-RECEPTOR | - |
dc.subject.keywordPlus | ALZHEIMERS-DISEASE | - |
dc.subject.keywordPlus | DIABETES-MELLITUS | - |
dc.subject.keywordPlus | TAU PHOSPHORYLATION | - |
dc.subject.keywordPlus | NUCLEAR RECEPTORS | - |
dc.subject.keywordPlus | BACE1 EXPRESSION | - |
dc.subject.keywordPlus | MOUSE MODEL | - |
dc.subject.keywordPlus | CHOLESTEROL | - |
dc.subject.keywordPlus | CALPAIN | - |
dc.subject.keywordPlus | BRAIN | - |
dc.subject.keywordAuthor | High glucose | - |
dc.subject.keywordAuthor | lipid raft | - |
dc.subject.keywordAuthor | SK-N-MC cells | - |
dc.subject.keywordAuthor | Alzheimer’s disease | - |
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