Hypoxia stimulates urokinase receptor expression through a heme protein-dependent pathway - PubMed (original) (raw)
. 1998 May 1;91(9):3300-7.
Affiliations
- PMID: 9558386
Free article
Hypoxia stimulates urokinase receptor expression through a heme protein-dependent pathway
C H Graham et al. Blood. 1998.
Free article
Abstract
Hypoxia underlies a number of biologic processes in which cellular migration and invasion occur. Because earlier studies have shown that the receptor for urokinase-type plasminogen activator (uPAR) may facilitate such events, we studied the effect of hypoxia on the expression of uPAR by first trimester human trophoblasts (HTR-8/SVneo) and human umbilical vein endothelial cells (HUVEC). Compared with control cells cultured under standard conditions (20% O2), HTR-8/SVneo cells and HUVEC cultured in 1% O2 expressed more uPAR, as determined by flow cytometric and [125I]-prourokinase ligand binding analyses. Increased uPAR expression paralleled increases in uPAR mRNA. The involvement of a heme protein in the hypoxia-induced expression of uPAR was suggested by the observations that culture of cells with cobalt chloride, or sodium 4, 5-dihydroxybenzene-1,3-disulfonate (Tiron), an iron-chelating agent, also stimulated uPAR expression, and that the hypoxia-induced uPAR expression was inhibited by adding carbon monoxide to the hypoxic atmosphere. Culture of HTR-8/SVneo cells with vascular endothelial growth factor (VEGF) did not increase uPAR mRNA levels, suggesting that the hypoxia-mediated effect on uPAR expression by these cells did not occur through a VEGF-dependent mechanism. The functional importance of these findings is suggested by the fact that HTR-8/SVneo cells cultured under hypoxia displayed higher levels of cell surface plasminogen activator activity and greater invasion through a reconstituted basement membrane. These results suggest that hypoxia may promote cellular invasion by stimulating the expression of uPAR through a heme protein-dependent pathway.
Similar articles
- Binding of high molecular weight kininogen to human endothelial cells is mediated via a site within domains 2 and 3 of the urokinase receptor.
Colman RW, Pixley RA, Najamunnisa S, Yan W, Wang J, Mazar A, McCrae KR. Colman RW, et al. J Clin Invest. 1997 Sep 15;100(6):1481-7. doi: 10.1172/JCI119669. J Clin Invest. 1997. PMID: 9294114 Free PMC article. - Hypoxia-mediated stimulation of carcinoma cell invasiveness via upregulation of urokinase receptor expression.
Graham CH, Forsdike J, Fitzgerald CJ, Macdonald-Goodfellow S. Graham CH, et al. Int J Cancer. 1999 Feb 9;80(4):617-23. doi: 10.1002/(sici)1097-0215(19990209)80:4<617::aid-ijc22>3.0.co;2-c. Int J Cancer. 1999. PMID: 9935166 - Biological significance of the expression of urokinase-type plasminogen activator receptors (uPARs) in brain tumors.
Mohanam S, Gladson CL, Rao CN, Rao JS. Mohanam S, et al. Front Biosci. 1999 Feb 15;4:D178-87. doi: 10.2741/mohanam. Front Biosci. 1999. PMID: 9989951 Review. - Regulation and role of urokinase plasminogen activator in vascular remodelling.
Tkachuk V, Stepanova V, Little PJ, Bobik A. Tkachuk V, et al. Clin Exp Pharmacol Physiol. 1996 Sep;23(9):759-65. doi: 10.1111/j.1440-1681.1996.tb01177.x. Clin Exp Pharmacol Physiol. 1996. PMID: 8911711 Review.
Cited by
- Hypoxia and angiogenesis: regulation of hypoxia-inducible factors via novel binding factors.
Chen L, Endler A, Shibasaki F. Chen L, et al. Exp Mol Med. 2009 Dec 31;41(12):849-57. doi: 10.3858/emm.2009.41.12.103. Exp Mol Med. 2009. PMID: 19942820 Free PMC article. Review. - Blood markers of fibrinolysis and endothelial activation in canine babesiosis.
Kuleš J, Gotić J, Mrljak V, Barić Rafaj R. Kuleš J, et al. BMC Vet Res. 2017 Mar 31;13(1):82. doi: 10.1186/s12917-017-0995-6. BMC Vet Res. 2017. PMID: 28363279 Free PMC article. - Adenosine A2B receptors induce proliferation, invasion and activation of cAMP response element binding protein (CREB) in trophoblast cells.
Darashchonak N, Koepsell B, Bogdanova N, von Versen-Höynck F. Darashchonak N, et al. BMC Pregnancy Childbirth. 2014 Jan 3;14:2. doi: 10.1186/1471-2393-14-2. BMC Pregnancy Childbirth. 2014. PMID: 24383849 Free PMC article. - Mechanism of maternal vascular remodeling during human pregnancy.
Sato Y, Fujiwara H, Konishi I. Sato Y, et al. Reprod Med Biol. 2011 Jul 16;11(1):27-36. doi: 10.1007/s12522-011-0102-9. eCollection 2012 Jan. Reprod Med Biol. 2011. PMID: 29699103 Free PMC article. Review. - Chromatin accessibility landscape and regulatory network of high-altitude hypoxia adaptation.
Xin J, Zhang H, He Y, Duren Z, Bai C, Chen L, Luo X, Yan DS, Zhang C, Zhu X, Yuan Q, Feng Z, Cui C, Qi X, Ouzhuluobu, Wong WH, Wang Y, Su B. Xin J, et al. Nat Commun. 2020 Oct 1;11(1):4928. doi: 10.1038/s41467-020-18638-8. Nat Commun. 2020. PMID: 33004791 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources