The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Hypoxia Promotes Glycogen Accumulation through Hypoxia Inducible Factor (HIF)-Mediated Induction of Glycogen Synthase 1
Open accessAbstract
When oxygen becomes limiting, cells reduce mitochondrial respiration and increase ATP production through anaerobic fermentation of glucose. The Hypoxia Inducible Factors (HIFs) play a key role in this metabolic shift by regulating the transcription of key enzymes of glucose metabolism. Here we show that oxygen regulates the expression of the muscle glycogen synthase (GYS1). Hypoxic GYS1 induction requires HIF activity and a Hypoxia Response Element within its promoter. GYS1 gene induction correlated with a significant increase in glycogen synthase activity and glycogen accumulation in cells exposed to hypoxia. Significantly, knockdown of either HIF1alpha or GYS1 attenuated hypoxia-induced glycogen accumulation, while GYS1 overexpression was sufficient to mimic this effect. Altogether, these results indicate that GYS1 regulation by HIF plays a central role in the hypoxic accumulation of glycogen. Importantly, we found that hypoxia also upregulates the expression of UTP:glucose-1-phosphate urydylyltransferase (UGP2) and 1,4-alpha glucan branching enzyme (GBE1), two enzymes involved in the biosynthesis of glycogen. Therefore, hypoxia regulates almost all the enzymes involved in glycogen metabolism in a coordinated fashion, leading to its accumulation. Finally, we demonstrated that abrogation of glycogen synthesis, by knock-down of GYS1 expression, impairs hypoxic preconditioning, suggesting a physiological role for the glycogen accumulated during chronic hypoxia. In summary, our results uncover a novel effect of hypoxia on glucose metabolism, further supporting the central importance of metabolic reprogramming in the cellular adaptation to hypoxia.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Jaakkola, P., Mole, D. R., Tian, Y.-M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A. V., Hebestreit, H. F., Mukherji, M., Schofield, C. J., et al. (2001) · Science · doi:10.1126/science.1059796 · Cited by 5,535
The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Maxwell, P. H., Wiesener, M. S., Chang, G.-W., Clifford, S. C., Vaux, E. C., Cockman, M. E., Wykoff, C. C., Pugh, C. W., Maher, E. R., & Ratcliffe, P. J. (1999) · Nature · doi:10.1038/20459 · Cited by 5,180
HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O 2 Sensing
Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J. M., Lane, W. S., & Kaelin Jr., W. G. (2001) · Science · doi:10.1126/science.1059817 · Cited by 4,735
Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes
Siepel, A., Bejerano, G., Pedersen, J. S., Hinrichs, A. S., Hou, M., Rosenbloom, K., Clawson, H., Spieth, J., Hillier, L. W., Richards, S., et al. (2005) · Genome Research · doi:10.1101/gr.3715005 · Cited by 3,971 · cited 1×
“Moreover, the HRE motif was included in a noncoding region conserved across vertebrates (figure 3A, PhastCons vertebrate track) [28].”
BackgroundKim, J.-W., Tchernyshyov, I., Semenza, G. L., & Dang, C. V. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.02.002 · Cited by 3,905
Huang, L. E., Gu, J., Schau, M., & Bunn, H. F. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.14.7987 · Cited by 2,113
Differential Roles of Hypoxia-Inducible Factor 1α (HIF-1α) and HIF-2α in Hypoxic Gene Regulation
Hu, C.-J., Wang, L.-Y., Chodosh, L. A., Keith, B., & Simon, M. C. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.24.9361-9374.2003 · Cited by 1,386
HIF-1 Regulates Cytochrome Oxidase Subunits to Optimize Efficiency of Respiration in Hypoxic Cells
Fukuda, R., Zhang, H., Kim, J.-W., Shimoda, L., Dang, C. V., & Semenza, G. L. (2007) · Cell · doi:10.1016/j.cell.2007.01.047 · Cited by 1,225
HIF-1α binding to VHL is regulated by stimulus-sensitive proline hydroxylation
Yu, F., White, S. B., Zhao, Q., & Lee, F. S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.181341498 · Cited by 796
Ivan, M., Haberberger, T., Gervasi, D. C., Michelson, K. S., Günzler, V., Kondo, K., Yang, H., Sorokina, I., Conaway, R. C., Conaway, J. W., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.192342099 · Cited by 561
Cited by
HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations
Semenza, G. L. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67230 · Cited by 1,335
Oxygen Sensing, Hypoxia-Inducible Factors, and Disease Pathophysiology
Semenza, G. L. (2014) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-012513-104720 · Cited by 1,159
Hypoxia-Inducible Factors: Master Regulators of Cancer Progression
Schito, L., & Semenza, G. L. (2016) · Trends in Cancer · doi:10.1016/j.trecan.2016.10.016 · Cited by 962
Hypoxia and Metabolic Adaptation of Cancer Cells
Eales, K. L., Hollinshead, K. E. R., & Tennant, D. A. (2016) · Oncogenesis · doi:10.1038/oncsis.2015.50 · Cited by 724
Favaro, E., Bensaad, K., Chong, M. G., Tennant, D. A., Ferguson, D. J. P., Snell, C., Steers, G., Turley, H., Li, J.-L., Günther, U. L., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.10.017 · Cited by 386
Metadata
- Authors
- Pescador, N., Villar, D., Cifuentes, D., Garcia-Rocha, M., Ortiz-Barahona, A., Vazquez, S., Ordoñez, A., Cuevas, Y., Saez-Morales, D., Garcia-Bermejo, M. L., Landazuri, M. O., Guinovart, J., & del Peso, L.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-03-12
- Volume
- 5
- Issue
- 3
- Pages
- e9644
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W1972633518
- Cited by
- 264
- References
- 10
- FWCI
- 3.34
- Type
- journal article
- Language
- en
- Open access
- gold
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Hypoxia Promotes Glycogen Accumulation through Hypoxia Inducible Factor (HIF)-Mediated Induction of Glycogen Synthase 1. https://app.cochat.ai/papers/10.1371/journal.pone.0009644
- The paper
- Pescador, N., Villar, D., Cifuentes, D., Garcia-Rocha, M., Ortiz-Barahona, A., Vazquez, S., Ordoñez, A., Cuevas, Y., Saez-Morales, D., Garcia-Bermejo, M. L., Landazuri, M. O., Guinovart, J., & del Peso, L. (2010). Hypoxia Promotes Glycogen Accumulation through Hypoxia Inducible Factor (HIF)-Mediated Induction of Glycogen Synthase 1. PLoS ONE. https://doi.org/10.1371/journal.pone.0009644
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
