Suppression of hERG K+ current and cardiac action potential prolongation by 4-hydroxynonenal via dual mechanisms
DC Field | Value | Language |
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dc.contributor.author | Choi, Seong Woo | - |
dc.contributor.author | Choi, Si Won | - |
dc.contributor.author | Jeon, Young Keul | - |
dc.contributor.author | Moon, Sung-Hwan | - |
dc.contributor.author | Zhang, Yin-Hua | - |
dc.contributor.author | Kim, Sung Joon | - |
dc.date.accessioned | 2024-01-09T03:31:19Z | - |
dc.date.available | 2024-01-09T03:31:19Z | - |
dc.date.issued | 2018-10 | - |
dc.identifier.issn | 2213-2317 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/69811 | - |
dc.description.abstract | Oxidative stress under pathological conditions, such as ischemia/reperfusion and inflammation, results in the production of various reactive chemicals. Of these chemicals, 4-hydroxynonenal (4-UNE), a peroxidation product of omega 6-polyunsaturated fatty acid, has garnered significant attention. However, the effect of 4-HNE on cardiac electrophysiology has not yet been reported. In the present study, we investigated the effects of 4-HNE on several cardiac ion channels, including human ether-a-go-go-related (hERG) channels, using the whole-cell patch clamp technique. Short-term exposure to 100 mu M 4-FINE (4-HNE100S), which mimics local levels under oxidative stress, decreased the amplitudes of rapidly activating delayed rectifier K+ current (I-Kr) in guinea pig ventricular myocytes (GPVMs) and HEK293T cells overexpressing hERG (I-hERG). MS analysis revealed the formation of 4-HNE-hERG adduct on specific amino acid residues, including C276, K595, H70, and H687. Longterm treatment (1-3 h) with 10 mu NI 4-HNE (4-HNE10L), suppressed I(Kr )and I-hERG, but not I-Ks, and I-ca,(L). Action potential duration (APD) of GPVMs was prolonged by 37% and 64% by 4-HNE100S and 4-HNE10L, respectively. Western blot analysis using surface biotinylation revealed a reduction in mature membrane hERG protein after treatment with 4-HNEio L. Proteasomal degradation inhibitors, such as bortezomib, prevented the 4-HNEloi,induced decrease in mature hERG, suggesting a retrograde degradation of membrane hERG due to 4-HNE. Taken together, 4-HNE100S and 4-HNE10L suppressed I-hERG via functional inhibition and downregulation of membrane expression of hERG, respectively. The exposure of 4-HNE under pathological oxidative stress may increase the risk of proarrhythmic events via APD prolongation. | - |
dc.format.extent | 10 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | ELSEVIER SCIENCE BV | - |
dc.title | Suppression of hERG K+ current and cardiac action potential prolongation by 4-hydroxynonenal via dual mechanisms | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.redox.2018.08.018 | - |
dc.identifier.bibliographicCitation | REDOX BIOLOGY, v.19, pp 190 - 199 | - |
dc.description.isOpenAccess | Y | - |
dc.identifier.wosid | 000449722100020 | - |
dc.identifier.scopusid | 2-s2.0-85052527363 | - |
dc.citation.endPage | 199 | - |
dc.citation.startPage | 190 | - |
dc.citation.title | REDOX BIOLOGY | - |
dc.citation.volume | 19 | - |
dc.type.docType | Article | - |
dc.publisher.location | 네델란드 | - |
dc.subject.keywordAuthor | Lipid peroxidant | - |
dc.subject.keywordAuthor | 4-hydroxynonenal | - |
dc.subject.keywordAuthor | hERG channel | - |
dc.subject.keywordAuthor | Cardiac action potential prolongation | - |
dc.subject.keywordPlus | LIPID-PEROXIDATION | - |
dc.subject.keywordPlus | QT PROLONGATION | - |
dc.subject.keywordPlus | OXIDATIVE STRESS | - |
dc.subject.keywordPlus | DOWN-REGULATION | - |
dc.subject.keywordPlus | CHANNEL | - |
dc.subject.keywordPlus | CARDIOTOXICITY | - |
dc.subject.keywordPlus | DETOXIFICATION | - |
dc.subject.keywordPlus | DEGRADATION | - |
dc.subject.keywordPlus | INVOLVEMENT | - |
dc.subject.keywordPlus | DYSFUNCTION | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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