Biopolym. Cell. 2013; 29(5):428-440.
http://dx.doi.org/10.7124/bc.000835
Дискусії
Проблема «початку» – формулювання і спроба аналізу
1Кордюм В. А., 2Шувалова Н. С.
  1. Інститут молекулярної біології і генетики НАН України
    Вул. Академіка Заболотного, 150, Київ, Україна, 03680
  2. ДУ «Інститут генетичної і регенеративної медицини НАМН України»
    вул. Вишгородська, 67, Київ, Україна, 04114

Abstract

На прикладі дихання сформульовано і проаналізовано проблему «початку». Під «початком» мається на увазі система молекулярного датчика та подавання на нього молекулярного сигналу, з яких запускається послідовний каскад молекулярних перетворень, що в кінцевому підсумку призводить до зміни фенотипу. На роль «початку» обрано найвивченіші (як датчики) перші учасники подій – молекулярний кисень, родини білків PHD і HIF та молекули, які безпосередньо з ними взаємодіють. Обговорено також наявність додаткових і альтернативних систем. Істотним моментом усієї регуляції є відсутність систем сигналінгу на зростання (вище необхідної, тобто гіпероксію) концентрації молекулярного кисню в клітині.
Keywords: білки PHD і HIF, системи сигналінгу, молекулярний кисень
Повний текст: (PDF, російською)

References

[1] Gibson D. G., Glass J. I., Lartigue C., Noskov V. N., Chuang R. Y., Algire M. A., Benders G. A., Montague M. G., Ma L., Moodie M. M., Merryman C., Vashee S., Krishnakumar R., Assad-Garcia N., Andrews-Pfannkoch C., Denisova E. A., Young L., Qi Z. Q., Segall-Shapiro T. H., Calvey C. H., Parmar P. P., Hutchison C. A. 3rd, Smith H. O., Venter J. C. Creation of a bacterial cell con trolled by a chemically synthesized genome Science 2010 329, N 5987:52–56.
[2] Brahimi-Horn M. C., Pouyssegur J. Oxygen, a source of life and stress FEBS Letters 2007 581, N 19:3582–3591.
[3] Braun R. D., Lanzen J. L., Snyder S. A., Dewhirst M. W. Comparison of tumor and normal tissue oxygen tension measurements using OxyLite or microelectrodes in rodents Am. J. Physiol. Heart Circ. Physiol 2001 280, N 6 H2533–2544.
[4] Erecinska M., Silver I. A. Tissue oxygen tension and brain sensitivity to hypoxia Respir. Physiol 2001 128, N 3:263–276.
[5] Siddiq A., Aminova L. R., Ratan R. R. Hypoxia inducible factor prolyl 4-hydroxylase enzymes: center stage in the battle against hypoxia, metabolic compromise and oxidative stress Neurochem Res 2007 32, N 4–5:931–946.
[6] McDonough M. A., Li V., Flashman E., Chowdhury R., Mohr C., Lienard B. M., Zondlo J., Oldham N. J., Clifton I. J., Lewis J., McNeill L. A.,Kurzeja R. J., Hewitson K. S., Yang E., Jordan S., Syed R. S., Schofield C. J. Cellular oxygen sensing: Crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2) Proc. Natl Acad. Sci. USA 2006 103, N 26:9814–9819.
[7] Choi K., Lee T., Lee N., Kim J. H., Yang E. G., Yoon J. M., Kim J. H., Lee T. G., Park H. Inhibition of the catalytic activity of hypoxia-inducible factor-1-prolyl-hydroxylase 2 by a MYND-type zinc finger Mol. Pharmacol 2005 68, N 68:1803–1809.
[8] Metzen E. Enzyme substrate recognition in oxygen sensing: how the HIF trap snaps Biochem. J 2007 408, N 2:e5–6.
[9] Dalgard C. L., Lu H., Mohyeldin A., Verma A. Endogenous 2oxoacids differentially regulate expression of oxygen sensors Biochem. J 2004 380, Pt 2:419–424.
[10] Schofield C. J., Ratcliffe P. J. Oxygen sensing by HIF hydroxylases Nat. Rev. Mol. Cell Biol 2004 5, N 5:343–354.
[11] Semenza G. L., Wang G. L. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation Mol. Cell Biol 1992 12, N 12:5447–5454.
[12] Shi Y. H., Fang W. G. Hypoxia-inducible factor-1 in tumour angiogenesis World J. Gastroenterol 2004 10, N 8:1082– 1087.
[13] Semenza G. L. Oxygen homeostasis Wiley Interdiscip. Rev. Syst. Biol. Med 2010 2, N 3:336–361.
[14] Wang G. L., Jiang B. H., Rue E. A., Semenza G. L. Hypoxia inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension Proc. Natl. Acad. Sci. USA 1995 92, N 12:5510–5514.
[15] Qutub A. A., Popel A. S. A computational model of intracellular oxygen sensing by hypoxia-inducible factor HIF1a J. Cell Sci 2006 119, Pt.16:3467–3480.
[16] Kaelin W. G. Jr., Ratcliffe P. J. Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway Mol. Cell 2008 30, N 4:393–402.
[17] Rankin E. B., Rha J., Selak M. A., Unger T. L., Keith B., Liu Q., Haase V. H. Hypoxia-inducible factor 2 regulates hepatic lipid metabolism Mol. Cell Biol 2009 29, N 16:4527–4538.
[18] Zagorska A., Dulak J. HIF-1: the knowns and unknowns of hypoxia sensing Acta Biochim. Pol 2004 51, N 3:563–585.
[19] Lisy K., Peet D. J. Turn me on: regulating HIF transcriptional activity Cell Death Differ 2008 15, N 4:642–649.
[20] Fulda S., Debatin K. M. HIF-1-regulated glucose metabolism: a key to apoptosis resistance? Cell Cycle 2007 6, N 7 P. 790–792.
[21] Haddad J. J. Oxygen-sensing mechanisms and the regulation of redox-responsive transcription factors in development and pathophysiology Respir. Res 2002 3:26.
[22] Fong G. H., Takeda K. Role and regulation of prolyl hydroxylase domain proteins Cell Death Differ 2008 15, N 4 P. 635–641.
[23] Metzen E., Berchner-Pfannschmidt U., Stengel P., Marxsen J. H., Stolze I., Klinger M., Huang W. Q., Wotzlaw C., Hellwig-Burgel T., Jelkmann W., Acker H., Fandrey J. Intracellular localisation of human HIF-1 alpha hydroxylases: implications for oxygen sensing J. Cell. Sci 2003 116, Pt 7:1319–1326.
[24] Hirsila M., Koivunen P., Gunzler V., Kivirikko K.I., Myllyharju J. Characterization of the human prolyl 4-hydroxylases that modify the hypoxia-inducible factor J. Biol. Chem 2003 278, N 33:30772–30780.
[25] Metzen E., Stiehl D. P., Doege K., Marxsen J. H., Hellwig-Burgel T., Jelkmann W. Regulation of the prolyl hydroxylase domain protein 2 (phd2/egln-1) gene: identification of a functional hypoxia-responsive element Biochem J 2005 387, Pt. 3 P. 711–717.
[26] Berra E., Ginouves A., Pouyssegur J. The hypoxia-induciblefactor hydroxylases bring fresh air into hypoxia signalling EMBO Rep 2006 7, N 1:41–45.
[27] Cervera A. M., Apostolova N., Luna-Crespo F., Sanjuan-Pla A., Garcia-Bou R., McCreath K. J. An alternatively spliced transcript of the PHD3 gene retains prolyl hydroxylase activity Cancer Lett 2006 233, N1:131–138.
[28] Chan D. A., Sutphin P. D., Yen S. E., Giaccia A. J. Coordinate regulation of the oxygen-dependent degradation domains of hypoxia-inducible factor 1 alpha Mol. Cell Biol 2005 25, N 15 P. 6415–6426.
[29] Ke Q., Costa M. Hypoxia-Inducible Factor-1 (HIF-1) Mol. Pharmacol 2006 70, N 5:1469–1480.
[30] Katschinski D. M. In vivo functions of the prolyl-4-hydroxylase domain oxygen sensors: direct route to the treatment of anaemia and the protection of ischaemic tissues Acta Physiol. (Oxf.) 2009 195, N 4:407–414.
[31] Soilleux E. J., Turley H., Tian Y. M., Pugh C. W., Gatter K. C., Harris A. L. Use of novel monoclonal antibodies to determine the expression and distribution of the hypoxia regulatory factors PHD-1, PHD-2, PHD-3 and FIH in normal and neoplastic human tissues Histopathology 2005 47, N 6:602–610.
[32] Tian H., McKnight S. L.,Russell D. W. Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells Genes Dev 1997 11, N 1:72–82.
[33] Covello K. L., Kehler J., Yu H., Gordan J. D., Arsham A. M., Hu C. J., Labosky P. A., Simon M. C., Keith B. HIF-2a regulates Oct4: effects of hypoxia on stem cell function, embryonic development, and tumor growth Genes Dev 2006 20, N 5–P. 557–570.
[34] Okuyama H., Krishnamachary B., Zhou Y.F., Nagasawa H., Bosch-Marce M., Semenza G. L. Expression of vascular endothelial growth factor receptor 1 in bone marrow-derived mesenchymal cells is dependent on hypoxia-inducible factor 1 J. Biol. Chem 2006 281, N 22:15554–15563.
[35] Gu Y. Z., Moran S. M., Hogenesch J. B., Wartman L., Bradfield C. A. Molecular characterization and chromosomal localization of a third alpha-class hypoxia inducible factor subunit, HIF3 alpha Gene Expr. 1998 7, N 3:205–213.
[36] Aragones J., Frais P., Baes M., Carmeliet P. Oxygen sensors at the crossroad of metabolism Cell Metabolism 2009 9, N 1 P. 11–22.
[37] Koivunen P., Hirsila M., Gunzler V., Kivirikko K.I., Myllyharju J. Catalytic properties of the asparaginyl hydroxylase (FIH) in the oxygen sensing pathway are distinct from those of its prolyl 4-hydroxylases J. Biol. Chem 2004 279, N 11:9899– 9904.
[38] Acker H. The oxygen sensing signal cascade under the influence of reactive oxygen species Philos Trans. R. Soc. Lond. B Biol. Sci 2005 360, N 1464–P. 2201–2210.
[39] Echevarria M., Munoz-Cabello A. M., Sanchez-Silva R., ToledoAral J. J., Lopez-Barneo J. Development of cytosolic hypoxia and HIF stabilization are facilitated by aquaporin 1 expression J. Biol. Chem 2007 282, N 41:30207–30215.
[40] Fink T., Abildtrup L., Fogd K., Abdallah B. M., Kassem M., Ebbesen P., Zachar V. Induction of adipocyte-like phenotype in human mesenchymal stem cells by hypoxia Stem Cells 2004 22, N 7:1346–1355.
[41] Haque N., Rahman M. T., Abu Kasim N. H., Alabsi A. M. Hypoxic culture conditions as a solution for mesenchymal stem cell based regenerative therapy Sci. World J 2013 2013:1–12.