| Organ preservation solutions attenuate accumulation and nuclear translocation of hypoxia-inducible factor-1alpha in the hepatoma cell line HepG2. | |
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MedLine Citation:
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PMID: 19821261 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Hypoxia-inducible factor-1alpha (HIF-1alpha) is a key transcription factor orchestrating hypoxic and inflammatory reactions. Here, we determined the impact of organ preservation solutions (Celsior; histidine-tryptophan-ketoglutarate solution, HTK; University of Wisconsin solution; UW), oxygen supply, and temperature on HIF-1alpha accumulation, recorded by Western blotting and immunocytochemistry, in the human hepatoma cell line HepG2. Generation of reactive oxygen species (ROS), NO, and cell viability were concomitantly assessed. At 4 degrees C, HIF-1alpha accumulation was not detectable. In normothermic (37 degrees C) cell culture medium (Dulbecco's Modified Eagle's Medium, DMEM), HepG2 cells accumulated HIF-1alpha even in normoxia (21% O(2)) which was not observed in either of the preservation solutions. This correlated to high generation of NO, a normoxic stabilizer of HIF-1alpha, and L-arginine content (substrate for NO synthesis) in DMEM, and low NO production and absence of L-arginine in preservation solutions. In normothermic hypoxia up to 24 h, intracellular HIF-1alpha accumulated in all conditions, but less in preservation solutions compared to DMEM. The inhibitory effect on accumulation and nuclear translocation was most prominent for HTK, the only solution containing the activator of HIF-1alpha degradation, alpha-ketoglutarate. Addition of other intermediates of the tricarbon acid cycle-succinate, fumarate, malate-did not alter HIF-1alpha accumulation, although succinate exhibited a beneficial effect on cell viability in cold storage. In conclusion, preservation solutions attenuate accumulation and nuclear translocation of the transcription factor HIF-1alpha, and this property is seemingly related to their chemical composition (L-arginine, alpha-ketoglutarate). Thus, it appears feasible to design preservation solution specifically to modify HIF-1alpha accumulation and nuclear translocation. |
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Authors:
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Renate Paddenberg; Nele Howold; Christiane Hoger; Hermann Janssen; Veronika Grau; Wolfgang Kummer |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Cell biochemistry and function Volume: 27 ISSN: 1099-0844 ISO Abbreviation: Cell Biochem. Funct. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-12-02 Completed Date: 2010-02-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8305874 Medline TA: Cell Biochem Funct Country: England |
Other Details:
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Languages: eng Pagination: 516-25 Citation Subset: IM |
Affiliation:
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Institute for Anatomy and Cell Biology, Justus-Liebig-University, Giessen, Germany. Renate.Paddenberg@anatomie.med.uni-giessen.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Active Transport, Cell Nucleus
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drug effects Anoxia / metabolism*, physiopathology Carcinoma, Hepatocellular / metabolism, physiopathology Cell Nucleus / drug effects, metabolism* Cell Survival / drug effects Hep G2 Cells Humans Hypoxia-Inducible Factor 1, alpha Subunit / metabolism* Liver Neoplasms / metabolism, physiopathology Organ Preservation Organ Preservation Solutions / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Organ Preservation Solutions |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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