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Prepublished online as a Blood First Edition Paper on May 31, 2002; DOI 10.1182/blood-2001-12-0169. This Article Full Text Full Text (PDF) All Versions of this Article: 2001-12-0169v1 100/7/2623    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Stolze, I. Articles by Fandrey, J. Search for Related Content PubMed PubMed Citation Articles by Stolze, I. Articles by Fandrey, J. Related Collections Red Cells Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 October 2002, Vol. 100, No. 7, pp. 2623-2628 RED CELLS Hypoxia-inducible erythropoietin gene expression in human neuroblastoma cells Ineke Stolze, Utta Berchner-Pfannschmidt, Patricia Freitag, Christoph Wotzlaw, Jochen Rössler, Stilla Frede, Helmut Acker, and Joachim Fandrey From the Institut für Physiologie der Universität Essen; Max-Planck-Institut für molekulare Physiologie, Dortmund; and Universitäts-Kinderklinik Freiburg, Germany. Two human neuroblastoma (NB) cell lines, SH-SY5Y and Kelly, were found to express the gene for erythropoietin (EPO) in an oxygen (O2)-dependent manner. However, NB cells had maximal production of EPO with lower partial pressure of O2 values than the well-characterized hepatoma cell line HepG2. This maximal EPO expression was preceded by accumulation of the O2-sensitive  subunit of the heterodimeric transcription-factor complex hypoxia-inducible factor 1 (HIF-1). Western blot analysis revealed that the amount of the  subunit of HIF-1, identical to aryl hydrocarbon receptor nuclear translocator 1 (ARNT1), and the homolog ARNT2 increased in nuclear extracts from SH-SY5Y cells exposed to anoxia. In neuronal cells, ARNT1 and ARNT2 can form a heterodimer with HIF-1, generating a functional HIF-1 complex. Using the hypoxia response element of the human EPO enhancer, we conducted electrophoretic mobility shift assays that showed accumulation and binding of HIF-1 complexes containing both ARNT1 and ARNT2 in NB cells. In addition to the HIF-1 complex, hepatocyte nuclear factor 4 (HNF4) was found to be indispensable for hypoxia-induced EPO gene expression in hepatoma cells. Western blot analysis and polymerase chain reaction assessment showed that NB cells express neither HNF4 nor the splicing variant HNF47 and thus express EPO in an HNF4-independent manner. Together, SH-SY5Y and Kelly cells may provide a new in vitro model for studying the mechanism of tissue-specific, hypoxia-inducible EPO gene expression. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: U. Berchner-Pfannschmidt, S. Frede, C. Wotzlaw, and J. Fandrey Imaging of the hypoxia-inducible factor pathway: insights into oxygen sensing Eur. Respir. J., July 1, 2008; 32(1): 210 - 217. [Abstract] [Full Text] [PDF] L. K. Martens, K. M. Kirschner, C. Warnecke, and H. Scholz Hypoxia-inducible Factor-1 (HIF-1) Is a Transcriptional Activator of the TrkB Neurotrophin Receptor Gene J. Biol. Chem., May 11, 2007; 282(19): 14379 - 14388. [Abstract] [Full Text] [PDF] U. Berchner-Pfannschmidt, H. Yamac, B. Trinidad, and J. Fandrey Nitric Oxide Modulates Oxygen Sensing by Hypoxia-inducible Factor 1-dependent Induction of Prolyl Hydroxylase 2 J. Biol. Chem., January 19, 2007; 282(3): 1788 - 1796. [Abstract] [Full Text] [PDF] M. D. Plotkin and M. S. Goligorsky Mesenchymal cells from adult kidney support angiogenesis and differentiate into multiple interstitial cell types including erythropoietin-producing fibroblasts Am J Physiol Renal Physiol, October 1, 2006; 291(4): F902 - F912. [Abstract] [Full Text] [PDF] J. C. Chavez, O. Baranova, J. Lin, and P. Pichiule The Transcriptional Activator Hypoxia Inducible Factor 2 (HIF-2/EPAS-1) Regulates the Oxygen-Dependent Expression of Erythropoietin in Cortical Astrocytes J. Neurosci., September 13, 2006; 26(37): 9471 - 9481. [Abstract] [Full Text] [PDF] J. Fandrey, T. A. Gorr, and M. Gassmann Regulating cellular oxygen sensing by hydroxylation Cardiovasc Res, September 1, 2006; 71(4): 642 - 651. [Abstract] [Full Text] [PDF] M. Puppo, S. Pastorino, G. Melillo, A. Pezzolo, L. Varesio, and M. C. Bosco Induction of Apoptosis by Flavopiridol in Human Neuroblastoma Cells Is Enhanced under Hypoxia and Associated With N-myc Proto-oncogene Down-Regulation Clin. Cancer Res., December 15, 2004; 10(24): 8704 - 8719. [Abstract] [Full Text] [PDF] U. Berchner-Pfannschmidt, F. Petrat, K. Doege, B. Trinidad, P. Freitag, E. Metzen, H. de Groot, and J. Fandrey Chelation of Cellular Calcium Modulates Hypoxia-inducible Gene Expression through Activation of Hypoxia-inducible Factor-1{alpha} J. Biol. Chem., October 22, 2004; 279(43): 44976 - 44986. [Abstract] [Full Text] [PDF] P. B. Freeburg and D. R. Abrahamson Divergent Expression Patterns for Hypoxia-Inducible Factor-1{beta} and Aryl Hydrocarbon Receptor Nuclear Transporter-2 in Developing Kidney J. Am. Soc. Nephrol., October 1, 2004; 15(10): 2569 - 2578. [Abstract] [Full Text] [PDF] Y. Ma, P. Freitag, J. Zhou, B. Brune, S. Frede, and J. 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