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http://doi.org/10.25358/openscience-8794Full metadata record
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.author | Gehrke, Nadine | - |
| dc.contributor.author | Wörns, Marcus A. | - |
| dc.contributor.author | Mann, Amrit | - |
| dc.contributor.author | Hövelmeyer, Nadine | - |
| dc.contributor.author | Waisman, Ari | - |
| dc.contributor.author | Straub, Beate K. | - |
| dc.contributor.author | Galle, Peter R. | - |
| dc.contributor.author | Schattenberg, Jörn M. | - |
| dc.date.accessioned | 2023-02-10T09:06:12Z | - |
| dc.date.available | 2023-02-10T09:06:12Z | - |
| dc.date.issued | 2022 | - |
| dc.identifier.uri | https://openscience.ub.uni-mainz.de/handle/20.500.12030/8810 | - |
| dc.description.abstract | Acute liver failure (ALF) is a rare entity but exhibits a high mortality. The mechanisms underlying ALF are not completely understood. The present study explored the role of the hepatic B cell leukemia-3 (Bcl-3), a transcriptional regulator of nuclear factor-kappa B (NF-κB), in two independent models of ALF. We employed a recently developed transgenic mouse model in a C57BL6/J background comparing wild-type (WT) and transgenic littermates with hepatocyte-specific overexpression of Bcl-3 (Bcl-3Hep) in the ALF model of d-galactosamine (d-GalN) and lipopolysaccharide (LPS). Additionally, the apoptosis-inducing CD95 (FAS/APO-1)-ligand was explored. Bcl-3Hep mice exhibited a significant protection from ALF with decreased serum transaminases, decreased activation of the apoptotic caspases 8, 9, and 3, lower rates of oxidative stress, B-cell lymphoma 2 like 1 (BCL2L1/BCL-XL) degradation and accompanying mitochondrial cytochrome c release, and ultimately a decreased mortality rate from d-GalN/LPS compared to WT mice. d-GalN/LPS treatment resulted in a marked inflammatory cytokine release and stimulated the activation of signal transducer and activator of transcription (STAT) 3, c-Jun N-terminal kinases (JNK) and extracellular signal-regulated kinase (ERK) signaling comparably in the hepatic compartment of Bcl-3Hep and WT mice. However, in contrast to the WT, Bcl-3Hep mice showed a diminished rate of IkappaB kinase-beta (IKK-β) degradation, persistent receptor interacting protein kinase (RIPK) 1 function and thus prolonged cytoprotective nuclear factor-kappa B (NF-κB) p65 signaling through increased p65 stability and enhanced transcription. Likewise, Bcl-3 overexpression in hepatocytes protected from ALF with massive hepatocyte apoptosis induced by the anti-FAS antibody Jo2. The protection was also linked to IKK-β stabilization. Overall, our study showed that Bcl-3 rendered hepatocytes more resistant to hepatotoxicity induced by d-GalN/LPS and FAS-ligand. Therefore, Bcl-3 appears to be a critical regulator of the dynamics in ALF through IKK-β. | en_GB |
| dc.description.sponsorship | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 491381577 | de |
| dc.language.iso | eng | de |
| dc.rights | CC BY | * |
| dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | * |
| dc.subject.ddc | 610 Medizin | de_DE |
| dc.subject.ddc | 610 Medical sciences | en_GB |
| dc.title | Hepatocyte Bcl-3 protects from death-receptor mediated apoptosis and subsequent acute liver failure | en_GB |
| dc.type | Zeitschriftenaufsatz | de |
| dc.identifier.doi | http://doi.org/10.25358/openscience-8794 | - |
| jgu.type.dinitype | article | en_GB |
| jgu.type.version | Published version | de |
| jgu.type.resource | Text | de |
| jgu.organisation.department | FB 04 Medizin | de |
| jgu.organisation.number | 2700 | - |
| jgu.organisation.name | Johannes Gutenberg-Universität Mainz | - |
| jgu.rights.accessrights | openAccess | - |
| jgu.journal.title | Cell death & disease | de |
| jgu.journal.volume | 13 | de |
| jgu.pages.alternative | 510 | de |
| jgu.publisher.year | 2022 | - |
| jgu.publisher.name | Nature Publishing Group | de |
| jgu.publisher.place | London | de |
| jgu.publisher.issn | 2041-4889 | de |
| jgu.organisation.place | Mainz | - |
| jgu.subject.ddccode | 610 | de |
| jgu.publisher.doi | 10.1038/s41419-022-04946-y | de |
| jgu.organisation.ror | https://ror.org/023b0x485 | - |
| jgu.subject.dfg | Lebenswissenschaften | de |
| Appears in collections: | DFG-491381577-G | |
Files in This Item:
| File | Description | Size | Format | ||
|---|---|---|---|---|---|
 | hepatocyte_bcl3_protects_from-20230210100315764.pdf | 3.48 MB | Adobe PDF | View/Open |