Glucose is necessary for stabilization of hypoxia-inducible factor-1alpha under hypoxia: contribution of the pentose phosphate pathway to this stabilization.
Summary of "Glucose is necessary for stabilization of hypoxia-inducible factor-1alpha under hypoxia: contribution of the pentose phosphate pathway to this stabilization."
In this study, we observed that low glucose or fructose reduces the increase in hypoxia-inducible factor-1alpha (HIF-1alpha) protein under hypoxic conditions. 6-Aminonicotinamide (6-AN), an inhibitor of the pentose phosphate pathway (PPP), also inhibited the increase of HIF-1alpha protein under hypoxic conditions, while the reduced protein levels of HIF-1alpha by low glucose were apparently recovered by the addition of MG-132 or NADPH. Moreover, siRNA for glucose-6-phosphate dehydrogenase, which produces NADPH, reduced the increase in HIF-1alpha protein. On the other hand, cobalt-induced expression of HIF-1alpha protein was not affected by low glucose or 6-AN under normoxic conditions. In conclusion, glucose metabolism through the PPP, but not in glycolysis, plays an important role in the stabilization of HIF-1alpha protein under hypoxic conditions.
Affiliation
Department of Pathological Biochemistry, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto, Japan. osada@med.osaka-cu.ac.jp
Journal Details
This article was published in the following journal.
Name: FEBS letters
ISSN: 1873-3468
Pages: 3073-9
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20621833
- DOI: http://dx.doi.org/10.1016/j.febslet.2010.05.046
Medical and Biotech [MESH] Definitions
Hypoxia-inducible Factor 1
A basic helix-loop-helix transcription factor that plays a role in APOPTOSIS. It is composed of two subunits: ARYL HYDROCARBON RECEPTOR NUCLEAR TRANSLOCATOR and HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT.
Hypoxia-inducible Factor 1, Alpha Subunit
Hypoxia-inducible factor 1, alpha subunit is a basic helix-loop-helix transcription factor that is regulated by OXYGEN availability and is targeted for degradation by VHL TUMOR SUPPRESSOR PROTEIN.
Von Hippel-lindau Tumor Suppressor Protein
A ubiquitin-protein ligase that mediates OXYGEN-dependent polyubiquitination of HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT. It is inactivated in VON HIPPEL-LINDAU SYNDROME.
Aryl Hydrocarbon Receptor Nuclear Translocator
Aryl hydrocarbon receptor nuclear translocator is a basic HELIX-LOOP-HELIX MOTIF containing protein that forms a complex with DIOXIN RECEPTOR. The complex binds xenobiotic regulatory elements and activates transcription of a variety of genes including UDP GLUCURONOSYLTRANSFERASE. AhR nuclear translocator is also a subunit of HYPOXIA-INDUCIBLE FACTOR 1.
Glucose Clamp Technique
Maintenance of a constant blood glucose level by perfusion or infusion with glucose or insulin. It is used for the study of metabolic rates (e.g., in glucose, lipid, amino acid metabolism) at constant glucose concentration.
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