The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Induction of Hypoxia-inducible Factor-1α by Transcriptional and Translational Mechanisms
Open accessAbstract
Hypoxia-inducible factor-1 (HIF-1) regulates the transcription of many genes induced by low oxygen conditions. Recent studies have demonstrated that non-hypoxic stimuli can also activate HIF-1 in a cell-specific manner. Here, we define two key mechanisms that are implicated in increasing the active subunit of the HIF-1 complex, HIF-1alpha, following the stimulation of vascular smooth muscle cells (VSMC) with angiotensin II (Ang II). We show that, in contrast to hypoxia, the induction of HIF-1alpha by Ang II in VSMC is dependent on active transcription and ongoing translation. We demonstrate that stimulation of VSMC by Ang II strongly increases HIF-1alpha gene expression. The activation of diacylglycerol-sensitive protein kinase C (PKC) plays a major role in the increase of HIF-1alpha gene transcription. We also demonstrate that Ang II relies on ongoing translation to maintain elevated HIF-1alpha protein levels. Ang II increases HIF-1alpha translation by a reactive oxygen species (ROS)-dependent activation of the phosphatidylinositol 3-kinase pathway, which acts on the 5'-untranslated region of HIF-1alpha mRNA. These results establish that the non-hypoxic induction of the HIF-1 transcription factor via vasoactive hormones (Ang II and thrombin) is triggered by a dual mechanism, i.e. a PKC-mediated transcriptional action and a ROS-dependent increase in HIF-1alpha protein expression. Elucidation of these signaling pathways that up-regulate the vascular endothelial growth factor (VEGF) could have a strong impact on different aspects of vascular biology.
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Hydrogen peroxide sensing, signaling and regulation of transcription factors
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The vascular NAD(P)H oxidases as therapeutic targets in cardiovascular diseases
Cai, H., Griendling, K. K., & Harrison, D. G. (2003) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(03)00233-5 · Cited by 687
Lactate in the tumour microenvironment: From immune modulation to therapy
Wang, Z.-H., Peng, W.-B., Zhang, P., Yang, X.-P., & Zhou, Q. (2021) · EBioMedicine · doi:10.1016/j.ebiom.2021.103627 · Cited by 528
The effect of HIF on metabolism and immunity
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Metadata
- Authors
- Pagé, E. L., Robitaille, G. A., Pouysségur, J., & Richard, D. E.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-12
- Volume
- 277
- Issue
- 50
- Pages
- 48403-48409
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2033453582
- Cited by
- 385
- References
- 37
- FWCI
- 8.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
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