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Status: Bibliographieeintrag

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Verfasst von:Ciuclan, Loredana Ioana [VerfasserIn]   i
 Ehnert, Sabrina [VerfasserIn]   i
 Ilkavets, Iryna [VerfasserIn]   i
 Weng, Honglei [VerfasserIn]   i
 Gaitantzi, Haristi [VerfasserIn]   i
 Tsukamoto, Hidekazu [VerfasserIn]   i
 Ueberham, Elke [VerfasserIn]   i
 Meindl-Beinker, Nadja M. [VerfasserIn]   i
 Singer, Manfred V. [VerfasserIn]   i
 Breitkopf-Heinlein, Katja [VerfasserIn]   i
 Dooley, Steven [VerfasserIn]   i
Titel:TGF-β enhances alcohol dependent hepatocyte damage via down-regulation of alcohol dehydrogenase I
Verf.angabe:Loredana Ciuclan, Sabrina Ehnert, Iryna Ilkavets, Hong-Lei Weng, Haristi Gaitantzi, Hidekazu Tsukamoto, Elke Ueberham, Nadja M. Meindl-Beinker, Manfred V. Singer, Katja Breitkopf, Steven Dooley
E-Jahr:2010
Jahr:6 January 2010
Umfang:10 S.
Fussnoten:Gesehen am 23.03.2023
Titel Quelle:Enthalten in: Journal of hepatology
Ort Quelle:Amsterdam [u.a.] : Elsevier Science, 1985
Jahr Quelle:2010
Band/Heft Quelle:52(2010), 3, Seite 407-416
ISSN Quelle:1600-0641
Abstract:BACKGROUND & AIMS: Adverse alcohol effects in the liver involve oxidative metabolism, fat deposition and release of fibrogenic mediators, including TGF-beta. The work presents an assessment of liver damaging cross-talk between ethanol and TGF-beta in hepatocytes. - METHODS: To investigate TGF-beta effects on hepatocytes, microarray analyses were performed and validated by qRT-PCR, Western blot analysis and immunohistochemistry. The cellular state was determined by assessing lactate dehydrogenase, cellular glutathione, reactive oxygen species, lipid peroxidation and neutral lipid deposition. RNA interference was used for gene silencing in vitro. - RESULTS: TGF-beta is induced in mouse livers after chronic ethanol insult, enhances ethanol induced oxidative stress and toxicity towards cultured hepatocytes plus induces lipid-, oxidative stress metabolism- and fibrogenesis-gene expression signatures. Interestingly, TGF-beta down-regulates alcohol metabolizing enzyme Adh1 mRNA in cultured hepatocytes and liver tissue from TGF-beta transgenic mice via the ALK5/Smad2/3 signalling branch, with Smad7 as a potent negative regulator. ADH1 deficiency is a determining factor for the increased lipid accumulation and Cyp2E1 dependent toxicity in liver cells upon alcohol challenge. Further, ADH1 expression was decreased during liver damage in an intragastric ethanol infusion mouse model. - CONCLUSION: In the presence of ethanol, TGF-beta displays pro-steatotic action in hepatocytes via decreasing ADH1 expression. Low ADH1 levels are correlated with enhanced hepatocyte damage upon chronic alcohol consumption by favoring secondary metabolic pathways.
DOI:doi:10.1016/j.jhep.2009.12.003
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1016/j.jhep.2009.12.003
 DOI: https://doi.org/10.1016/j.jhep.2009.12.003
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Alcohol Dehydrogenase
 Animals
 Cells, Cultured
 Chemical and Drug Induced Liver Injury
 Disease Models, Animal
 Down-Regulation
 Ethanol
 Hepatocytes
 Lipid Metabolism
 Lipid Peroxidation
 Male
 Mice
 Mice, Inbred C57BL
 Oxidative Stress
 Protein Serine-Threonine Kinases
 Receptor, Transforming Growth Factor-beta Type I
 Receptors, Transforming Growth Factor beta
 Signal Transduction
 Smad7 Protein
 Transforming Growth Factor beta
K10plus-PPN:183991369X
Verknüpfungen:→ Zeitschrift

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