دورية أكاديمية
أعرض في EDS

MG132 dramatically reduces SAA expression in chicken hepatocellular carcinoma cells at the transcript level independent of its endogenous promoter.

التفاصيل البيبلوغرافية
العنوان: MG132 dramatically reduces SAA expression in chicken hepatocellular carcinoma cells at the transcript level independent of its endogenous promoter.
المؤلفون: Paul NF; Department of Animal Sciences, Division of Functional Breeding, Georg-August-Universität Göttingen, Burckhardtweg 2, 37077, Göttingen, Germany., Gustmann K; Department of Animal Sciences, Division of Functional Breeding, Georg-August-Universität Göttingen, Burckhardtweg 2, 37077, Göttingen, Germany., Tetens J; Department of Animal Sciences, Division of Functional Breeding, Georg-August-Universität Göttingen, Burckhardtweg 2, 37077, Göttingen, Germany.; Center for Integrated Breeding Research, Georg-August-University, Albrecht-Thaer-Weg 3, 37075, Göttingen, Germany., Falker-Gieske C; Department of Animal Sciences, Division of Functional Breeding, Georg-August-Universität Göttingen, Burckhardtweg 2, 37077, Göttingen, Germany. clemens.falker-gieske@uni-goettingen.de.; Center for Integrated Breeding Research, Georg-August-University, Albrecht-Thaer-Weg 3, 37075, Göttingen, Germany. clemens.falker-gieske@uni-goettingen.de.
المصدر: Molecular biology reports [Mol Biol Rep] 2024 Jun 19; Vol. 51 (1), pp. 770. Date of Electronic Publication: 2024 Jun 19.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Reidel Country of Publication: Netherlands NLM ID: 0403234 Publication Model: Electronic Cited Medium: Internet ISSN: 1573-4978 (Electronic) Linking ISSN: 03014851 NLM ISO Abbreviation: Mol Biol Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Dordrecht, Boston, Reidel.
مواضيع طبية MeSH: Leupeptins*/pharmacology , Chickens*/genetics , Carcinoma, Hepatocellular*/genetics , Carcinoma, Hepatocellular*/metabolism , Carcinoma, Hepatocellular*/drug therapy , Liver Neoplasms*/genetics , Liver Neoplasms*/metabolism , Liver Neoplasms*/drug therapy , Promoter Regions, Genetic*/genetics , Serum Amyloid A Protein*/genetics , Serum Amyloid A Protein*/metabolism , NF-kappa B*/metabolism, Animals ; Cell Line, Tumor ; Proteasome Endopeptidase Complex/metabolism ; Proteasome Endopeptidase Complex/genetics ; Proteasome Inhibitors/pharmacology ; Gene Expression Regulation, Neoplastic/drug effects
مستخلص: Background: MG132, a proteasome inhibitor, is widely used to inhibit nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity by proteasome-mediated degradation of IκB. It has been marketed as a specific, reversible, cell-permeable and low-cost inhibitor. However, adverse effects of the compound have been reported in the literature. We recently discovered and characterised a point mutation in the acute phase protein serum amyloid A (SAA) in chickens, by overexpressing the protein in chicken hepatocellular carcinoma (LMH) cells. This serine to arginine exchange at amino acid position 90 (SAA.R90S) leads to intra- and extracellular accumulation of SAA, which is surprisingly counteracted by MG132 treatment, independent of SAA's intrinsic promoter.
Methods and Results: To test, whether low proteasomal degradation of SAA.R90S is responsible for the observed intra- and extracellular SAA accumulation, we intended to inhibit the proteasome in SAA wild type (SAA.WT) overexpressing cells with MG132. However, we observed an unexpected drastic decrease in SAA protein expression at the transcript level. NF-κB gene expression was unchanged by MG132 at the measured time point.
Conclusions: The observed results demonstrate that MG132 inhibits SAA expression at the transcript level, independent of its endogenous promoter. Further, the data might indicate that NF-κB is not involved in the observed MG132-induced inhibition of SAA expression. We, consequently, question in this brief report whether MG132 should truly be categorised as a specific ubiquitin proteasome inhibitor and recommend the usage of alternative compounds.
(© 2024. The Author(s).)
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فهرسة مساهمة: Keywords: MG132; NF-κB; SAA; Serum amyloid A
المشرفين على المادة: RF1P63GW3K (benzyloxycarbonylleucyl-leucyl-leucine aldehyde)
0 (Leupeptins)
0 (Serum Amyloid A Protein)
0 (NF-kappa B)
EC 3.4.25.1 (Proteasome Endopeptidase Complex)
0 (Proteasome Inhibitors)
تواريخ الأحداث: Date Created: 20240619 Date Completed: 20240619 Latest Revision: 20240622
رمز التحديث: 20240622
مُعرف محوري في PubMed: PMC11186868
DOI: 10.1007/s11033-024-09726-9
PMID: 38896168
قاعدة البيانات: MEDLINE
الوصف
تدمد:1573-4978
DOI:10.1007/s11033-024-09726-9