scbmtБИОМЕДИЦИНАJournal Biomed2074-59822713-0428Scientific center of biomedical technologies of Federal Medical and Biological Agencyscbmt-901Research ArticleСтатьиМодулирование действия ядерных рецепторов и регуляция биотрансформации лекарствЛаринаС. Н.noemail@neicon.ruЧебышевН. В.noemail@neicon.ruШихЕ. В.noemail@neicon.ruКаркищенкоВ. Н.noemail@neicon.ruММА им. И.М.Сеченова, МоскваRussian FederationНаучный центр биомедицинских технологий РАМН, МоскваRussian Federation200913022020127080Copyright © Ларина С.Н., Чебышев Н.В., Ших Е.В., Каркищенко В.Н., 20202020Ларина С.Н., Чебышев Н.В., Ших Е.В., Каркищенко В.Н.Ларина С.Н., Чебышев Н.В., Ших Е.В., Каркищенко В.Н.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.scbmt.ru/jour/article/view/901

Ядерные рецепторы являются транскрипционными факторами, которые играют важную роль в ходе эмбрионального развития, поддержании дифференцировки клеток, метаболизме. Лиганд- регулируемый ядерный PXR рецептор, взаимодействует с разнообразными химическими ли- гандами и лекарственными препаратами и регулирует экспрессию генов, которые участвуют в метаболизме ксенобиотиков и лекарств. Строение этого рецептора обеспечивает связыва- ние с широким спектром лигандов, которые могут действовать как агонисты или антагонисты. Изучение модуляции действия ядерных рецепторов важно для разработки лекарственных пре- паратов, регулирующих метаболизм, а также при изучении взаимодействия лекарств.

ядерные рецепторыPXR рецепторбиотрансформация ксенобиотиковCYP3A4 цитохромReferencesВarwick J.L., Quattrochi L.C., Mills A.S. et al. Trans-species gene transfer for analysis of glucocorticoid-inducible transcriptional activation of transiently expressed human CYP3A4 and rabbit CYP3A6 in primary cultures of adult rat and rabbit hepatocytes // Mol. Pharmacol., 50:10-16, 1996.Вarwick J.L., Quattrochi L.C., Mills A.S. et al. Trans-species gene transfer for analysis of glucocorticoid-inducible transcriptional activation of transiently expressed human CYP3A4 and rabbit CYP3A6 in primary cultures of adult rat and rabbit hepatocytes // Mol. Pharmacol., 50:10-16, 1996.Drocourt L., Ourlin J.C., Pascussi J.M. et al. Expression of CYP3A4, CYP2B6, and CYP2C9 is regulated by the vitamin D receptor pathway in primary human hepatocytes // J. Biol Chem., 277:25125-25132, 2002.Drocourt L., Ourlin J.C., Pascussi J.M. et al. Expression of CYP3A4, CYP2B6, and CYP2C9 is regulated by the vitamin D receptor pathway in primary human hepatocytes // J. Biol Chem., 277:25125-25132, 2002.Glass C.K. Differential recognition of target genes by nuclear receptor monomers, dimeres, and heterodimeres // Endocrinol. Rev., 15: 391, 407, 1994.Glass C.K. Differential recognition of target genes by nuclear receptor monomers, dimeres, and heterodimeres // Endocrinol. Rev., 15: 391, 407, 1994.Greschic H., Moras D. Structure - activity relationship of nuclear receptor - ligand interactions // Curr. Top. Med. Chem., 3:1573-1599, 2003.Greschic H., Moras D. Structure - activity relationship of nuclear receptor - ligand interactions // Curr. Top. Med. Chem., 3:1573-1599, 2003.Gronemeyer H., Gustaffson J. A., Laudet V. Principles for modulation of the nuclear receptor superfamily // Nature Rev. Drug Discovery, 3: 950-964, 2004.Gronemeyer H., Gustaffson J. A., Laudet V. Principles for modulation of the nuclear receptor superfamily // Nature Rev. Drug Discovery, 3: 950-964, 2004.Hermanson O., Glass C.K., Rosenfeld M.G. Nuclear receptor coregulators: multiple modes of modification // Trends Endocrinol Metab., 13:55-60, 2002.Hermanson O., Glass C.K., Rosenfeld M.G. Nuclear receptor coregulators: multiple modes of modification // Trends Endocrinol Metab., 13:55-60, 2002.HonkakoskiP.,NegishiM. Characterization of a Phenobarbital-responsive enhancer module in mouse P450 Cyp2b10 gene // J. Biol Chem., 272:14943-14949, 1997.HonkakoskiP.,NegishiM. Characterization of a Phenobarbital-responsive enhancer module in mouse P450 Cyp2b10 gene // J. Biol Chem., 272:14943-14949, 1997.Jordan V.C. Antioestrogens and selective oestrogen receptor modulators as multifunctional medicines. Clinical considerations and new agents // J. Med. Chem., 46 1081-1111, 2003.Jordan V.C. Antioestrogens and selective oestrogen receptor modulators as multifunctional medicines. Clinical considerations and new agents // J. Med. Chem., 46 1081-1111, 2003.Kliewer S.A., Moore J.T., Wade L. et al. An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway // Cell 92:73-82, 1998.Kliewer S.A., Moore J.T., Wade L. et al. An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway // Cell 92:73-82, 1998.Kliewer S.A., Goodwin B., Wilson T.M. The nuclear pregnane X receptor: a key regulator of xenobiotic metabolism // Endocr. Rev., 23:687-702, 2002.Kliewer S.A., Goodwin B., Wilson T.M. The nuclear pregnane X receptor: a key regulator of xenobiotic metabolism // Endocr. Rev., 23:687-702, 2002.Kliewer S.A. The nuclear pregnane receptor regulates xenobiotic detoxification // J. Nutr. 133: 2444-2447, 2003.Kliewer S.A. The nuclear pregnane receptor regulates xenobiotic detoxification // J. Nutr. 133: 2444-2447, 2003.Kocarek T.A., Schuetz E.G., Guzelian P.S. Differentiated induction of cytochrome P450b/e and P450p mRNAs by dose of Phenobarbital in primary cultures of adult rat hepatocytes // Mol. Pharmacol., 38:440-444, 1990.Kocarek T.A., Schuetz E.G., Guzelian P.S. Differentiated induction of cytochrome P450b/e and P450p mRNAs by dose of Phenobarbital in primary cultures of adult rat hepatocytes // Mol. Pharmacol., 38:440-444, 1990.Kodama S., Koike C., Negishi M., Yamomoto Y. Nuclear receptors Car and PXR cross talk with FOXO1 to regulate genes that encode drug-metabolizing and gluconeogenic enzymes // Mol. Cell Biol., 24:7931-7940, 2004.Kodama S., Koike C., Negishi M., Yamomoto Y. Nuclear receptors Car and PXR cross talk with FOXO1 to regulate genes that encode drug-metabolizing and gluconeogenic enzymes // Mol. Cell Biol., 24:7931-7940, 2004.Kushner P.J. et. Al. Estrogen receptor pathways to AP-1 // J. Steroid Biochem. Mol. Biol., 74, 311-317, 2000.Kushner P.J. et. Al. Estrogen receptor pathways to AP-1 // J. Steroid Biochem. Mol. Biol., 74, 311-317, 2000.Krasowski M.D., Yasuda K., Hagey L.R. et al. Evolution of the pregnane X receptor: adaptation to cross - species differences in biliary bile salts // Mol. Endocrinol., 19 : 1720-1739, 2005.Krasowski M.D., Yasuda K., Hagey L.R. et al. Evolution of the pregnane X receptor: adaptation to cross - species differences in biliary bile salts // Mol. Endocrinol., 19 : 1720-1739, 2005.Lee C.H., Olson P., Evans R.M. Lipid Metabolism, metabolic diseases, and peroxisome proliferator-activated receptors // Endocrinology, 144, 2201-2207, 2003.Lee C.H., Olson P., Evans R.M. Lipid Metabolism, metabolic diseases, and peroxisome proliferator-activated receptors // Endocrinology, 144, 2201-2207, 2003.Lehmann J.M., Mckee D.D., Watson M.A. et al. The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions // J. Clin. Unvest., 102:1016-1023, 1998.Lehmann J.M., Mckee D.D., Watson M.A. et al. The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions // J. Clin. Unvest., 102:1016-1023, 1998.Liu M.M. et. al. Oppossing action of estrogen receptors α and β on cyclin D1 gene expression // J. Biol. Chem., 277, 24353-24360, 2000.Liu M.M. et. al. Oppossing action of estrogen receptors α and β on cyclin D1 gene expression // J. Biol. Chem., 277, 24353-24360, 2000.Mangelsdorf D.G. , Evans R.M. The RXR heterodimeres and orphan receptors // Cell, 83:841-850, 1995.Mangelsdorf D.G. , Evans R.M. The RXR heterodimeres and orphan receptors // Cell, 83:841-850, 1995.Moore L.B., Parks D.J., Jones S.A. et al. Orphan nuclear receptors constitutive androstane receptor and pregnane X receptor share xenobiotic and steroid ligands // J. Biol. Chem., 275:15122-15127, 2000.Moore L.B., Parks D.J., Jones S.A. et al. Orphan nuclear receptors constitutive androstane receptor and pregnane X receptor share xenobiotic and steroid ligands // J. Biol. Chem., 275:15122-15127, 2000.Moore L.B., Maglich J.M., McKee D.D. et al. Pregnane X receptor (PXR), constitutive androstane receptor (CAR), and benzoate X receptor (BXR) define three pharmacologically distinct classes of nuclear receptors // Mol. Endocrinol., 16:977-986, 2002.Moore L.B., Maglich J.M., McKee D.D. et al. Pregnane X receptor (PXR), constitutive androstane receptor (CAR), and benzoate X receptor (BXR) define three pharmacologically distinct classes of nuclear receptors // Mol. Endocrinol., 16:977-986, 2002.Orans J., Teotico D.J., Redinbo M.R. The nuclear xenobiotic receptor Pregnane X Receptor: recent insights and new challenges // Mol. Endocrinol., 19: 2891-2900, 2005.Orans J., Teotico D.J., Redinbo M.R. The nuclear xenobiotic receptor Pregnane X Receptor: recent insights and new challenges // Mol. Endocrinol., 19: 2891-2900, 2005.Repa J.J., Turley S.D., Lobaccaro J.A., et al. Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers // Science, 289:1524-1529, 2000.Repa J.J., Turley S.D., Lobaccaro J.A., et al. Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers // Science, 289:1524-1529, 2000.Saradhi M., Kumar N., Reddy R.C., Tyagi R.K. Pregnane and xenobiotic receptor (PXR): a promiscuous xenosensor in human health and disease // J.E.R., 10 (1): 1-12, 2006.Saradhi M., Kumar N., Reddy R.C., Tyagi R.K. Pregnane and xenobiotic receptor (PXR): a promiscuous xenosensor in human health and disease // J.E.R., 10 (1): 1-12, 2006.Savas U., Wester M.R., Griffin K.J., Johnson E.F. Rabbit pregnane X receptor is activated by rifampicin // Drug Metab. Dispos., 28:529-537, 2000.Savas U., Wester M.R., Griffin K.J., Johnson E.F. Rabbit pregnane X receptor is activated by rifampicin // Drug Metab. Dispos., 28:529-537, 2000.Shang Y., Hu X., Di Renzo J. et al. Cofactor dynamics and sufficiency in estrogen receptor-regylated transcription // Cell, 103, 843-852, 2000.Shang Y., Hu X., Di Renzo J. et al. Cofactor dynamics and sufficiency in estrogen receptor-regylated transcription // Cell, 103, 843-852, 2000.Shang Y., Brown, M. Molecular determinants for the tissue specificity of SERMs // Science, 295, 2465-2468, 2002.Shang Y., Brown, M. Molecular determinants for the tissue specificity of SERMs // Science, 295, 2465-2468, 2002.Shulman A.I., Mangelsdorf D.J. Retinoid X receptor heterodimers in the metabolic syndrome // N. Engl. J. Med., 353:604-615, 2005.Shulman A.I., Mangelsdorf D.J. Retinoid X receptor heterodimers in the metabolic syndrome // N. Engl. J. Med., 353:604-615, 2005.Staudinger J., Liu Y., Madan A. et al. Coordinate regulation of xenobiotic and bile acid homeostasis by pregnane X receptor // Drug Metab. Dispos., 29:3369-3374, 2001.Staudinger J., Liu Y., Madan A. et al. Coordinate regulation of xenobiotic and bile acid homeostasis by pregnane X receptor // Drug Metab. Dispos., 29:3369-3374, 2001.Sonoda J., Chong L.W., Downes M. et al. Pregnane X receptor prevents hepatorenal toxicity from cholesterol metabolites // Proc. Natl. Acad. Sci. USA, 102:2198-2203, 2005.Sonoda J., Chong L.W., Downes M. et al. Pregnane X receptor prevents hepatorenal toxicity from cholesterol metabolites // Proc. Natl. Acad. Sci. USA, 102:2198-2203, 2005.Synold T.W., Dussault I., Forman B.M. The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux // Nat. Med., 7:584-590, 2001.Synold T.W., Dussault I., Forman B.M. The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux // Nat. Med., 7:584-590, 2001.Wan Y.J., An D., Cai Y. et al. Hepatocyte- specific mutation establishes retinoid X receptor alpha as a heterodimeric integrator of multiple physiological processes in the liver // Mol. Cell Biol., 20:4436-44, 2000.Wan Y.J., An D., Cai Y. et al. Hepatocyte- specific mutation establishes retinoid X receptor alpha as a heterodimeric integrator of multiple physiological processes in the liver // Mol. Cell Biol., 20:4436-44, 2000.Watkins R.E., Wisely G.B., Moore L.B. et al. The human nuclear xenobiotic receptor PXR: structural determinants of directed promiscuity // Science, 292:2329- 2333, 2001.Watkins R.E., Wisely G.B., Moore L.B. et al. The human nuclear xenobiotic receptor PXR: structural determinants of directed promiscuity // Science, 292:2329- 2333, 2001.Xie W., Barwick J.L., Simon C.M. et al. Reciprocal activation of xenobiotic response genes by nuclear receptors SXR/PXR and CAR // Genes Dev., 14:3014-3023, 2000.Xie W., Barwick J.L., Simon C.M. et al. Reciprocal activation of xenobiotic response genes by nuclear receptors SXR/PXR and CAR // Genes Dev., 14:3014-3023, 2000.

The authors declare that there are no conflicts of interest present.