The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Activation of the hypoxia‐inducible factor pathway and stimulation of angiogenesis by application of prolyl hydroxylase inhibitors
Abstract
Hypoxia‐inducible transcription factors (HIF) mediate complex adaptations to reduced oxygen supply, including neoangiogenesis. Regulation of HIF occurs mainly through oxygen‐dependent destruction of its α subunit. In the presence of oxygen, two HIFα prolyl residues undergo enzymatic hydroxylation, which is required for its proteasomal degradation. We therefore tested whether pharmacological activation of HIFα by hydroxylase inhibitors may provide a novel therapeutic strategy for the treatment of ischemic diseases. Three distinct prolyl 4‐hydroxylase inhibitors— l ‐mimosine ( l ‐Mim), ethyl 3,4‐dihydroxybenzoate (3,4‐DHB), and 6‐chlor‐3‐hydroxychinolin‐2‐carbonic acid‐N‐carboxymethylamid (S956711)—demonstrated similar effects to hypoxia (0.5% O 2 ) by inducing HIFα protein in human and rodent cells. l ‐Mim, S956711, and, less effectively, 3,4‐DHB also induced HIF target genes in cultured cells, including glucose transporter 1 and vascular endothelial growth factor, as well as HIF‐dependent reporter gene expression. Systemic administration of l ‐Mim and S956711 in rats led to HIFα induction in the kidney. In a sponge model for angiogenesis, repeated local injection of the inhibitors strongly increased invasion of highly vascularized tissue into the sponge centers. In conclusion, structurally distinct inhibitors of prolyl hydroxylation are capable of inducing HIFα and HIF target genes in vitro and in vivo and induce adaptive responses to hypoxia, including angiogenesis.
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Cites
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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
Self-citationHIFα 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
Asparagine Hydroxylation of the HIF Transactivation Domain: A Hypoxic Switch
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“21 mM in vitro and in cultured cells (5, 7).”
BackgroundSelf-citationLee, P. J., Jiang, B.-H., Chin, B. Y., Iyer, N. V., Alam, J., Semenza, G. L., & Choi, A. K. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.9.5375 · Cited by 782
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Cited by
Targeting Hypoxia-Inducible Factors for the Treatment of Anemia in Chronic Kidney Disease Patients
Locatelli, F., Fishbane, S., Block, G. A., & Macdougall, I. C. (2017) · American Journal of Nephrology · doi:10.1159/000455166 · Cited by 4,813
Oxygen sensing by HIF hydroxylases
Schofield, C. J., & Ratcliffe, P. J. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1366 · Cited by 2,068
Weidemann, A., & Johnson, R. S. (2008) · Cell Death & Differentiation · doi:10.1038/cdd.2008.12 · Cited by 941
Self-citationTargeting hypoxia signalling for the treatment of ischaemic and inflammatory diseases
Eltzschig, H. K., Bratton, D. L., & Colgan, S. P. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4422 · Cited by 366
Inhibition of Prolyl Hydroxylases Increases Erythropoietin Production in ESRD
Bernhardt, W. M., Wiesener, M. S., Scigalla, P., Chou, J., Schmieder, R. E., Günzler, V., & Eckardt, K.-U. (2010) · Journal of the American Society of Nephrology · doi:10.1681/asn.2010010116 · Cited by 340
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Metadata
- Authors
- Warnecke, C., Griethe, W., Weidemann, A., Jürgensen, J. S., Willam, C., Bachmann, S., Ivashchenko, Y., Wagner, I., Frei, U., Wiesener, M., & Eckardt, K.-U.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2003-04-22
- Volume
- 17
- Issue
- 9
- Pages
- 1186-1188
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2079844104
- Cited by
- 200
- References
- 12
- FWCI
- 5.32
- Type
- journal article
- Language
- en
- Open access
- closed
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- Warnecke, C., Griethe, W., Weidemann, A., Jürgensen, J. S., Willam, C., Bachmann, S., Ivashchenko, Y., Wagner, I., Frei, U., Wiesener, M., & Eckardt, K.-U. (2003). Activation of the hypoxia‐inducible factor pathway and stimulation of angiogenesis by application of prolyl hydroxylase inhibitors. The FASEB Journal. https://doi.org/10.1096/fj.02-1062fje
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