The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Hyperglycemia Regulates Hypoxia-Inducible Factor-1α Protein Stability and Function
Open accessAbstract
Hyperglycemia and hypoxia are suggested to play essential pathophysiological roles in the complications of diabetes, which may result from a defective response of the tissues to low oxygen tension. In this study, we show that in primary dermal fibroblasts and endothelial cells, hyperglycemia interferes with the function of hypoxia-inducible factor-1 (HIF-1), a transcription factor that is essential for adaptive responses of the cell to hypoxia. Experiments using proteasomal and prolyl hydroxylases inhibitors indicate that hyperglycemia inhibits hypoxia-induced stabilization of HIF-1α protein levels against degradation and suggest that mechanisms in addition to proline hydroxylation may be involved. This effect of hyperglycemia was dose dependent and correlates with a lower transcription activation potency of HIF-1α, as assessed by transient hypoxia-inducible reporter gene assay. Regulation of HIF-1α function by hyperglycemia could be mimicked by mannitol, suggesting hyperosmolarity as one critical parameter. The interference of hyperglycemia with hypoxia-dependent stabilization of HIF-1α protein levels was confirmed in vivo, where only very low levels of HIF-1α protein could be detected in diabetic wounds, as compared with chronic venous ulcers. In conclusion, our data demonstrate that hyperglycemia impairs hypoxia-dependent protection of HIF-1α against proteasomal degradation and suggest a mechanism by which diabetes interferes with cellular responses to hypoxia.
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Cites
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Biochemistry and molecular cell biology of diabetic complications
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HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O 2 Sensing
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Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage
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A conserved family of prolyl-4-hydroxylases that modify HIF
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Role of HIF-1α in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis
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Cellular and developmental control of O 2 homeostasis by hypoxia-inducible factor 1α
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Cited by
Regulation of hypoxia-inducible factor-1α by NF-κB
van Uden, P., Kenneth, N. S., & Rocha, S. (2008) · Biochemical Journal · doi:10.1042/bj20080476 · Cited by 729
Hypoxia and mitochondrial oxidative metabolism
Solaini, G., Baracca, A., Lenaz, G., & Sgarbi, G. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.02.011 · Cited by 608
Stabilization of HIF-1α is critical to improve wound healing in diabetic mice
Botusan, I. R., Sunkari, V. G., Savu, O., Catrina, A. I., Grünler, J., Lindberg, S., Pereira, T., Ylä-Herttuala, S., Poellinger, L., Brismar, K., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805230105 · Cited by 533
Self-citationHypoxia signaling in human health and diseases: implications and prospects for therapeutics
Luo, Z., Tian, M., Yang, G., Tan, Q., Chen, Y., Li, G., Zhang, Q., Li, Y., Wan, P., & Wu, J. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01080-1 · Cited by 499
Hypoxia and hypoxia-inducible factors in diabetes and its complications
Catrina, S.-B., & Zheng, X. (2021) · Diabetologia · doi:10.1007/s00125-021-05380-z · Cited by 400
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Metadata
- Authors
- Catrina, S.-B., Okamoto, K., Pereira, T., Brismar, K., & Poellinger, L.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2004-12-01
- Volume
- 53
- Issue
- 12
- Pages
- 3226-3232
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2098379861
- Cited by
- 384
- References
- 48
- FWCI
- 2.94
- Type
- journal article
- Language
- en
- Open access
- bronze
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