Methylglyoxal-Induced Dysfunction in Brain Endothelial Cells via the Suppression of Akt/HIF-1 alpha Pathway and Activation of Mitophagy Associated with Increased Reactive Oxygen Species
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Donghyun | - |
dc.contributor.author | Kim, Kyeong-A | - |
dc.contributor.author | Kim, Jeong-Hyeon | - |
dc.contributor.author | Kim, Eun-Hye | - |
dc.contributor.author | Bae, Ok-Nam | - |
dc.date.accessioned | 2021-06-22T06:00:20Z | - |
dc.date.available | 2021-06-22T06:00:20Z | - |
dc.date.issued | 2020-09 | - |
dc.identifier.issn | 2076-3921 | - |
dc.identifier.issn | 2076-3921 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/925 | - |
dc.description.abstract | Methylglyoxal (MG) is a dicarbonyl compound, the level of which is increased in the blood of diabetes patients. MG is reported to be involved in the development of cerebrovascular complications in diabetes, but the exact mechanisms need to be elucidated. Here, we investigated the possible roles of oxidative stress and mitophagy in MG-induced functional damage in brain endothelial cells (ECs). Treatment of MG significantly altered metabolic stress as observed by the oxygen-consumption rate and barrier-integrity as found in impaired trans-endothelial electrical resistance in brain ECs. The accumulation of MG adducts and the disturbance of the glyoxalase system, which are major detoxification enzymes of MG, occurred concurrently. Reactive oxygen species (ROS)-triggered oxidative damage was observed with increased mitochondrial ROS production and the suppressed Akt/hypoxia-inducible factor 1 alpha (HIF-1 alpha) pathway. Along with the disturbance of mitochondrial bioenergetic function, parkin-1-mediated mitophagy was increased by MG. Treatment of N-acetyl cysteine significantly reversed mitochondrial damage and mitophagy. Notably, MG induced dysregulation of tight junction proteins including occludin, claudin-5, and zonula occluden-1 in brain ECs. Here, we propose that diabetic metabolite MG-associated oxidative stress may contribute to mitochondrial damage and autophagy in brain ECs, resulting in the dysregulation of tight junction proteins and the impairment of permeability. | - |
dc.format.extent | 17 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | MDPI | - |
dc.title | Methylglyoxal-Induced Dysfunction in Brain Endothelial Cells via the Suppression of Akt/HIF-1 alpha Pathway and Activation of Mitophagy Associated with Increased Reactive Oxygen Species | - |
dc.type | Article | - |
dc.publisher.location | 스위스 | - |
dc.identifier.doi | 10.3390/antiox9090820 | - |
dc.identifier.scopusid | 2-s2.0-85090514834 | - |
dc.identifier.wosid | 000580698400001 | - |
dc.identifier.bibliographicCitation | ANTIOXIDANTS, v.9, no.9, pp 1 - 17 | - |
dc.citation.title | ANTIOXIDANTS | - |
dc.citation.volume | 9 | - |
dc.citation.number | 9 | - |
dc.citation.startPage | 1 | - |
dc.citation.endPage | 17 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalResearchArea | Food Science & Technology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Medicinal | - |
dc.relation.journalWebOfScienceCategory | Food Science & Technology | - |
dc.subject.keywordPlus | INDUCED APOPTOSIS | - |
dc.subject.keywordPlus | OXIDATIVE STRESS | - |
dc.subject.keywordPlus | MITOCHONDRIAL DYSFUNCTION | - |
dc.subject.keywordPlus | PLASMA METHYLGLYOXAL | - |
dc.subject.keywordPlus | GLYOXALASE SYSTEM | - |
dc.subject.keywordPlus | AUTOPHAGY | - |
dc.subject.keywordPlus | ACCUMULATION | - |
dc.subject.keywordPlus | INFLAMMATION | - |
dc.subject.keywordPlus | MAINTENANCE | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordAuthor | methylglyoxal | - |
dc.subject.keywordAuthor | hypoxia-inducible factor 1 (HIF-1 alpha) | - |
dc.subject.keywordAuthor | mitophagy | - |
dc.subject.keywordAuthor | oxidative stress | - |
dc.subject.keywordAuthor | brain endothelial cells | - |
dc.identifier.url | https://www.mdpi.com/2076-3921/9/9/820/htm | - |
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