FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3080234966> ?p ?o ?g. }

• W3080234966 abstract "Abstract Background It is unknown whether liver sinusoidal endothelial cells (LSECs) metabolize alcohol. Chronic alcohol consumption decreases endothelial nitric oxide synthase (eNOS)-derived NO production typical of LSEC dysfunction. Heat shock protein 90 (Hsp90) interacts with eNOS to increase its activity. Cytochrome P450 2E1 (CYP2E1) is a key enzyme in alcohol metabolism and facilitates protein acetylation via acetyl-CoA, but its expression in LSECs is unknown. This study investigates alcohol metabolism by LSECs, the mechanism of alcohol-induced LSEC dysfunction and a potential therapeutic approach for alcohol-induced liver injury. Methods Primary human, rat and mouse LSECs were used. Histone deacetylase 6 (HDAC6) was overexpressed specifically in liver ECs using an adeno-associated virus (AAV)-mediated gene delivery system to decrease Hsp90 acetylation in ethanol fed mice. Results LSECs expressed CYP2E1 and alcohol dehydrogenase 1 (ADH1) and metabolized alcohol. Ethanol induced CYP2E1 in LSECs, but not ADH1. Alcohol metabolism by CYP2E1 increased Hsp90 acetylation and decreased its interaction with eNOS along with a decrease in NO production. A non-acetylation mutant of Hsp90 increased its interaction with eNOS and NO production, whereas a hyper-acetylation mutant decreased NO production, compared with wildtype Hsp90. These results indicate that Hsp90 acetylation is responsible for decreases in its interaction with eNOS and eNOS-derived NO production. Adeno-associated virus 8 (AAV8)-driven HDAC6 overexpression specifically in liver ECs deacetylated Hsp90, restored Hsp90’s interaction with eNOS and ameliorated alcohol-induced liver injury in mice. Conclusion Restoring LSEC function is important for ameliorating alcohol-induced liver injury. To this end, blocking acetylation of Hsp90 specifically in LSECs via AAV-mediated gene delivery has the potential to be a new therapeutic strategy." @default.
• W3080234966 created "2020-09-01" @default.
• W3080234966 creator A5012657842 @default.
• W3080234966 creator A5013087884 @default.
• W3080234966 creator A5019471332 @default.
• W3080234966 creator A5026090669 @default.
• W3080234966 creator A5053416071 @default.
• W3080234966 creator A5066961097 @default.
• W3080234966 creator A5082021081 @default.
• W3080234966 creator A5089828764 @default.
• W3080234966 date "2020-08-25" @default.
• W3080234966 modified "2023-10-16" @default.
• W3080234966 title "Alcohol-induced Hsp90 acetylation is a novel driver of liver sinusoidal endothelial dysfunction and alcoholic liver disease" @default.
• W3080234966 cites W1025953877 @default.
• W3080234966 cites W1553826095 @default.
• W3080234966 cites W1678800844 @default.
• W3080234966 cites W1967396537 @default.
• W3080234966 cites W1976912626 @default.
• W3080234966 cites W1981634237 @default.
• W3080234966 cites W1989268736 @default.
• W3080234966 cites W1994637279 @default.
• W3080234966 cites W1995188356 @default.
• W3080234966 cites W1996782134 @default.
• W3080234966 cites W1997361397 @default.
• W3080234966 cites W2003272885 @default.
• W3080234966 cites W2007399590 @default.
• W3080234966 cites W2010629576 @default.
• W3080234966 cites W2012457700 @default.
• W3080234966 cites W2012992997 @default.
• W3080234966 cites W2013161374 @default.
• W3080234966 cites W2018735093 @default.
• W3080234966 cites W2022137876 @default.
• W3080234966 cites W2032435016 @default.
• W3080234966 cites W2033522281 @default.
• W3080234966 cites W2036834058 @default.
• W3080234966 cites W2041105109 @default.
• W3080234966 cites W2044451058 @default.
• W3080234966 cites W2049423751 @default.
• W3080234966 cites W2050830506 @default.
• W3080234966 cites W2067740038 @default.
• W3080234966 cites W2070647828 @default.
• W3080234966 cites W2075502040 @default.
• W3080234966 cites W2077005457 @default.
• W3080234966 cites W2081094284 @default.
• W3080234966 cites W2090786177 @default.
• W3080234966 cites W2095203795 @default.
• W3080234966 cites W2102405052 @default.
• W3080234966 cites W2109190750 @default.
• W3080234966 cites W2112236420 @default.
• W3080234966 cites W2114026423 @default.
• W3080234966 cites W2160935294 @default.
• W3080234966 cites W2167188228 @default.
• W3080234966 cites W2171623299 @default.
• W3080234966 cites W2606824156 @default.
• W3080234966 cites W2736062522 @default.
• W3080234966 cites W2898537477 @default.
• W3080234966 cites W2937656853 @default.
• W3080234966 cites W2964534721 @default.
• W3080234966 cites W2974328440 @default.
• W3080234966 doi "https://doi.org/10.1101/2020.08.25.267096" @default.
• W3080234966 hasPublicationYear "2020" @default.
• W3080234966 type Work @default.
• W3080234966 sameAs 3080234966 @default.
• W3080234966 citedByCount "0" @default.
• W3080234966 crossrefType "posted-content" @default.
• W3080234966 hasAuthorship W3080234966A5012657842 @default.
• W3080234966 hasAuthorship W3080234966A5013087884 @default.
• W3080234966 hasAuthorship W3080234966A5019471332 @default.
• W3080234966 hasAuthorship W3080234966A5026090669 @default.
• W3080234966 hasAuthorship W3080234966A5053416071 @default.
• W3080234966 hasAuthorship W3080234966A5066961097 @default.
• W3080234966 hasAuthorship W3080234966A5082021081 @default.
• W3080234966 hasAuthorship W3080234966A5089828764 @default.
• W3080234966 hasBestOaLocation W30802349661 @default.
• W3080234966 hasConcept C104317684 @default.
• W3080234966 hasConcept C119157956 @default.
• W3080234966 hasConcept C126322002 @default.
• W3080234966 hasConcept C134018914 @default.
• W3080234966 hasConcept C140027455 @default.
• W3080234966 hasConcept C185592680 @default.
• W3080234966 hasConcept C205260736 @default.
• W3080234966 hasConcept C2775932338 @default.
• W3080234966 hasConcept C2776637226 @default.
• W3080234966 hasConcept C2777075537 @default.
• W3080234966 hasConcept C2777214474 @default.
• W3080234966 hasConcept C2777344606 @default.
• W3080234966 hasConcept C2777560012 @default.
• W3080234966 hasConcept C2777575235 @default.
• W3080234966 hasConcept C2777622882 @default.
• W3080234966 hasConcept C2778326061 @default.
• W3080234966 hasConcept C2781066024 @default.
• W3080234966 hasConcept C519581460 @default.
• W3080234966 hasConcept C526171541 @default.
• W3080234966 hasConcept C55493867 @default.
• W3080234966 hasConcept C62231903 @default.
• W3080234966 hasConcept C71924100 @default.
• W3080234966 hasConcept C86803240 @default.
• W3080234966 hasConcept C98274493 @default.
• W3080234966 hasConceptScore W3080234966C104317684 @default.
• W3080234966 hasConceptScore W3080234966C119157956 @default.

• next