The Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT/HIF-1β) is influenced by hypoxia and hypoxia-mimetics

作者: Matthias Wolff , Wolfgang Jelkmann , Jürgen Dunst , Reinhard Depping

DOI: 10.1159/000354487

关键词: Aryl hydrocarbon receptor nuclear translocatorCell biologyCell nucleusCellAryl hydrocarbon receptorTranscriptional regulationCell cultureChemistryHypoxia-inducible factorsLigand (biochemistry)

摘要: Background: The Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT, HIF-1β) is a member of the basic-Helix-Loop-Helix PER/ARNT/SIM (bHLH/PAS) protein family and vital transcriptional regulator regarding development physiological adaptation processes. ARNT discussed to be linked with cancer, other diseases. known translocated into cell nucleus, where accumulation takes place. heterodimerisation partner xenobiotic ligand activated (AhR), Single Minded proteins (SIM), cardiovascular helix-loop-helix factor 1 Hypoxia Inducible Factor (HIF-α). obligatory for HIF-1, HIF-2 HIF-3 binding DNA. Whereas degradation HIF-α subunits suppressed by hypoxia, generally regarded as constitutively expressed in excess within cell, stabilisation commonly thought oxygen-independent. However, we provide evidence that regulation far more complex. aim our study was reevaluate expression. Methods: We examined lines different origin like MCF-7 T47D (human breast cancer), HeLa cervix carcinoma), Hep3B HepG2 hepatoma), Kelly neuroblastoma), REPC kidney) Cos7 (primary primate cells. used immunoblot analysis, densitometry, RT-PCR transient transfection. Results Conclusion: Our results show levels are influenced hypoxia mimetics such cobalt(II)-chloride (CoCl2) dimethyloxalylglycine (DMOG) line specific manner. demonstrate this effect might triggered HIF-1α which plays an important role process stabilizing hypoxia.

参考文章(23)
Ivica Kvietikova, Dmitri Chilov, Urs Ziegler, Gieri Camenisch, Max Gassmann, Roland H. Wenger, Induction and nuclear translocation of hypoxia-inducible factor-1 (HIF-1): heterodimerization with ARNT is not necessary for nuclear accumulation of HIF-1alpha. Journal of Cell Science. ,vol. 112, pp. 1203- 1212 ,(1999) , 10.1242/JCS.112.8.1203
Hiroko Nakabayashi, Yasuharu Ohta, Masayoshi Yamamoto, Yosuke Susuki, Akihiko Taguchi, Katsuya Tanabe, Manabu Kondo, Masayuki Hatanaka, Yuko Nagao, Yukio Tanizawa, Clock-controlled output gene Dbp is a regulator of Arnt/Hif-1β gene expression in pancreatic islet β-cells Biochemical and Biophysical Research Communications. ,vol. 434, pp. 370- 375 ,(2013) , 10.1016/J.BBRC.2013.03.084
Roland H. Wenger, Andreas Rolfs, Hugo H. Marti, Christian Bauer, Max Gassmann, Hypoxia, a novel inducer of acute phase gene expression in a human hepatoma cell line. Journal of Biological Chemistry. ,vol. 270, pp. 27865- 27870 ,(1995) , 10.1074/JBC.270.46.27865
K Lisy, D J Peet, Turn me on: regulating HIF transcriptional activity. Cell Death & Differentiation. ,vol. 15, pp. 642- 649 ,(2008) , 10.1038/SJ.CDD.4402315
Michael T Chin, Koji Maemura, Shinya Fukumoto, Mukesh K Jain, Matthew D Layne, Masafumi Watanabe, Chung-Ming Hsieh, Mu-En Lee, None, Cardiovascular Basic Helix Loop Helix Factor 1, a Novel Transcriptional Repressor Expressed Preferentially in the Developing and Adult Cardiovascular System Journal of Biological Chemistry. ,vol. 275, pp. 6381- 6387 ,(2000) , 10.1074/JBC.275.9.6381
E B Rankin, A J Giaccia, The role of hypoxia-inducible factors in tumorigenesis. Cell Death & Differentiation. ,vol. 15, pp. 678- 685 ,(2008) , 10.1038/CDD.2008.21
Larissa A. Shimoda, Gregg L. Semenza, HIF and the lung: role of hypoxia-inducible factors in pulmonary development and disease. American Journal of Respiratory and Critical Care Medicine. ,vol. 183, pp. 152- 156 ,(2011) , 10.1164/RCCM.201009-1393PP
Hyunsung Choi, Yang-Sook Chun, Seung-Won Kim, Myung-Suk Kim, Jong-Wan Park, Curcumin inhibits hypoxia-inducible factor-1 by degrading aryl hydrocarbon receptor nuclear translocator: a mechanism of tumor growth inhibition. Molecular Pharmacology. ,vol. 70, pp. 1664- 1671 ,(2006) , 10.1124/MOL.106.025817
S. Shi, D.Y. Yoon, K. Hodge-Bell, S. Huerta-Yepez, O. Hankinson, Aryl Hydrocarbon Nuclear Translocator (Hypoxia Inducible Factor 1β) activity is required more during early than late tumor growth Molecular Carcinogenesis. ,vol. 49, pp. 157- 165 ,(2010) , 10.1002/MC.20585
Stilla Frede, Patricia Freitag, Luise Geuting, Rebecca Konietzny, Joachim Fandrey, Oxygen-regulated expression of the erythropoietin gene in the human renal cell line REPC. Blood. ,vol. 117, pp. 4905- 4914 ,(2011) , 10.1182/BLOOD-2010-07-298083