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Titel: ER stress inhibition enhances formation of triacylglcerols and protects endothelial cells from lipotoxicity
Autor(en): Kovačević, IgorIn der Gemeinsamen Normdatei der DNB nachschlagen
Schmidt, Paula Henriette
Kowalski, Annkatrin
Helms, Bernd J.
Lest, Christiaan Hendrikus AdriaanIn der Gemeinsamen Normdatei der DNB nachschlagen
Kluttig, AlexanderIn der Gemeinsamen Normdatei der DNB nachschlagen
Posern, GuidoIn der Gemeinsamen Normdatei der DNB nachschlagen
Erscheinungsdatum: 2024
Art: Artikel
Sprache: Englisch
Zusammenfassung: Elevated concentrations of palmitate in serum of obese individuals can impair endothelial function, contributing to development of cardiovascular disease. Although several molecular mechanisms of palmitate-induced endothelial dysfunction have been proposed, there is no consensus on what signaling event is the initial trigger of detrimental palmitate effects. Here we report that inhibitors of ER stress or ceramid synthesis can rescue palmitate-induced autophagy impairment in macro- and microvascular endothelial cells. Furthermore, palmitate-induced cholesterol synthesis was reverted using these inhibitors. Similar to cell culture data, autophagy markers were increased in serum of obese individuals. Subsequent lipidomic analysis revealed that palmitate changed the composition of membrane phospholipids in endothelial cells and that these effects were not reverted upon application of above-mentioned inhibitors. However, ER stress inhibition in palmitate-treated cells enhanced the synthesis of trilglycerides and restored ceramide levels to control condition. Our results suggest that palmitate induces ER-stress presumably by shift in membrane architecture, leading to impaired synthesis of triglycerides and enhanced production of ceramides and cholesterol, which altogether enhances lipotoxicity of palmitate in endothelial cells.
URI: https://opendata.uni-halle.de//handle/1981185920/120061
http://dx.doi.org/10.25673/118102
Open-Access: Open-Access-Publikation
Nutzungslizenz: (CC BY 4.0) Creative Commons Namensnennung 4.0 International(CC BY 4.0) Creative Commons Namensnennung 4.0 International
Journal Titel: Cell communication and signaling
Verlag: Biomed Central
Verlagsort: London
Band: 22
Originalveröffentlichung: 10.1186/s12964-024-01682-y
Seitenanfang: 1
Seitenende: 21
Enthalten in den Sammlungen:Open Access Publikationen der MLU

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