Nonhypoxic pathway mediates the induction of hypoxia-inducible factor 1alpha in vascular smooth muscle cells
- PMID: 10837481
- DOI: 10.1074/jbc.M003325200
Nonhypoxic pathway mediates the induction of hypoxia-inducible factor 1alpha in vascular smooth muscle cells
Abstract
Hypoxia-inducible factor-1 (HIF-1) controls the expression of a number of genes such as vascular endothelial growth factor (VEGF) and Erythropoietin in low oxygen conditions (hypoxia). VEGF is strongly induced at both the mRNA and protein expression level by a number of hormones and growth factors in vascular smooth muscle cells (VSMC) independently of the oxygen environment. However, the role of HIF-1alpha in this induction has not been studied. We report here that HIF-1alpha protein levels are strongly increased by fetal calf serum in quiescent VSMC. More interestingly, Angiotensin II (Ang II), thrombin, platelet-derived growth factor, and other hormones can also increase HIF-1alpha in VSMC to levels that are substantially more elevated than the hypoxic treatment. HIF-1alpha induced by Ang II is located in the nucleus, binds to the hypoxic response element, and is transcriptionally active. The induction of HIF-1alpha by hormones is mediated through the production of reactive oxygen species (ROS), since it can be blocked by the ROS inhibitors, diphenyleneiodonium and catalase. Finally, strong induction of VEGF mRNA by Ang II can also be inhibited by these ROS inhibitors. These results implicate HIF-1alpha and HIF-1-dependent transcriptional activity in the induction of VEGF expression after agonist stimulation and define novel hypoxia-independent mechanisms that should play a major role in vascular remodeling.
Similar articles
-
Hypoxia-induced angiogenesis during carcinogenesis.J Biochem Mol Biol. 2003 Jan 31;36(1):120-7. doi: 10.5483/bmbrep.2003.36.1.120. J Biochem Mol Biol. 2003. PMID: 12542982 Review.
-
Induction of hypoxia-inducible factor-1alpha by transcriptional and translational mechanisms.J Biol Chem. 2002 Dec 13;277(50):48403-9. doi: 10.1074/jbc.M209114200. Epub 2002 Oct 11. J Biol Chem. 2002. PMID: 12379645
-
Thrombin activates the hypoxia-inducible factor-1 signaling pathway in vascular smooth muscle cells: Role of the p22(phox)-containing NADPH oxidase.Circ Res. 2001 Jul 6;89(1):47-54. doi: 10.1161/hh1301.092678. Circ Res. 2001. PMID: 11440977
-
The molecular response of mammalian cells to hypoxia and the potential for exploitation in cancer therapy.Br J Cancer Suppl. 1996 Jul;27:S126-32. Br J Cancer Suppl. 1996. PMID: 8763864 Free PMC article. Review.
-
Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1.Mol Cell Biol. 1996 Sep;16(9):4604-13. doi: 10.1128/MCB.16.9.4604. Mol Cell Biol. 1996. PMID: 8756616 Free PMC article.
Cited by
-
Genetic Variations Related to Angiotensin II Production and Risk for Basal Cell Carcinoma.Biochem Genet. 2024 Mar 28. doi: 10.1007/s10528-024-10746-0. Online ahead of print. Biochem Genet. 2024. PMID: 38546913 Review.
-
MCJ: A mitochondrial target for cardiac intervention in pulmonary hypertension.Sci Adv. 2024 Jan 19;10(3):eadk6524. doi: 10.1126/sciadv.adk6524. Epub 2024 Jan 19. Sci Adv. 2024. PMID: 38241373 Free PMC article.
-
Protein kinase B/AKT phosphorylates hypoxia-inducible factor-3α1 in response to insulin, promoting cell growth and migration.Front Cell Dev Biol. 2023 Nov 9;11:1250000. doi: 10.3389/fcell.2023.1250000. eCollection 2023. Front Cell Dev Biol. 2023. PMID: 38020884 Free PMC article.
-
Proliferative Effect of Aqueous Extract of Sea Cucumber (Holothuria parva) Body Wall on Human Umbilical Cord Mesenchymal Stromal/Stem Cells.Mar Drugs. 2023 Apr 26;21(5):267. doi: 10.3390/md21050267. Mar Drugs. 2023. PMID: 37233461 Free PMC article.
-
Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions.Signal Transduct Target Ther. 2023 Feb 17;8(1):70. doi: 10.1038/s41392-023-01332-8. Signal Transduct Target Ther. 2023. PMID: 36797231 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous