Nükleer Reseptörler

Yıl 2023, Cilt: 20 Sayı: 1, 64 - 71, 03.04.2023

Yasin Kırtıl Murat Kanbur

https://doi.org/10.32707/ercivet.1258954

Öz

Gen ifadesinin kontrolü, modern moleküler biyolojinin merkezi ve önemli bir amacı haline gelmiştir. Nükleer resep- törler, tipik olarak hedef genler ile birlikte DNA yanıt elementlerine bağlanarak genetik ifadeyi düzenler. Son yıllarda yapılan araştırmalar, nükleer reseptör ailesinin, vücudun içindeki birçok kimyasal düzeyindeki dalgalanmalara karşı vücudun tepkisine esas faktör olduğunu ortaya koymuştur. Nükleer reseptörler metabolizma, homeostaz, farklılaşma, büyüme ve gelişme, yaşlanma ve üretim (hücre yenilenmesi) gibi birçok fizyolojik süreçte önemli roller oynar. Nükleer reseptör fonksiyonları çok karmaşıktır ve birbiri ile bağlantılıdır. Bu karmaşıklığa rağmen nükleer reseptör ailesi önemli ilaç hedefleri olarak yer almaktadır. Bu derlemede insan ve hayvanlarda bulunan nükleer reseptör ailesi ve fonksiyonla- rı hakkında bilgiler verildi.

Anahtar Kelimeler

Genetik ifade, hücre yenilenmesi, ilaç hedefleri, nükleer reseptörler, steroid reseptör

Nuclear Receptors

Öz

Control of gene expression has become a central theme in modern molecular biology. nuclear receptors typically regulate gene expression through binding to DNA response elements associated with target genes. Research over the past decade has demonstrated that the nuclear receptor family is intrinsic to the body’s response to fluctuations in the levels of many chemicals within the body. Nuclear receptors play an important role in many physiological processes such as metabolism, homeostasis, differentiation, growth and development, aging, and reproduction. Functions of nuclear receptors are highly complex and connected with each other. Despite this complexity, the nuclear receptor family has had a long history of successful drug discovery. With this review, it was given about nuclear receptor family and its functions in human and animals.

Anahtar Kelimeler

Cell expression, drug targets, genetic expression, nuclear receptors, steroid receptor

Kaynakça

• Aksoy H. Deneysel koledok kanal tıkanıklığı sonrası oluşan bakteriyel translokasyon üzerine taurourso deoksikolik asit ve moksifloksasinin etkisi, Uzmanlık Tezi, Trakya Üniv Tıp Fakültesi, Edirne, 2012; s. 43.
• Anderson KM, Gayer CP. The pathophysiology of farnesoid X receptor (FXR) in the GI tract: inflammation, barrier function and innate immunity. Cells 2021; 10(11): 3206.
• Arck P, Toth B, Pestka A, Jeschke U. Nuclear receptors of the peroxisome proliferator-activated receptor (PPAR) family in gestational diabetes: from animal models to clinical trials. Biol Reprod 2010; 83 (2): 168-76.
• Aydoğan HY, Kurt Ö, Kurnaz Ö, Teker BA, Küçükhü- seyin Ö. Koroner kalp hastalığında peroksizom proliferatör-aktive reseptör (PPAR) izoformları. Turk J Biochem 2013; 38(4): 372-84.
• Bunce MC, Campbeel JM. Nuclear receptors (Volume 8). Bunce MC, Springer, London, 2010: pp. 1-327.
• Ceydilek B, Beyler AR. Safra oluşumunda rol oyna- yan transport proteinleri. J Ankara Univ Fac Med 2005; 58: 68-72.
• Chen T. Nuclear receptor drug discovery. Curr Opin Chem Biol 2008; 12(4): 418-26.
• Çelik R. İlaç-reseptör etkileşimi ve stereokimyasal faktörler, Farmasötik Kimya Anabilim Dalı Bitirme Tezi, Erciyes Üniversitesi Eczacılık Fakültesi, 2013: s. 70.
• Deckmyn B, Domenger D, Blondel C, Ducastel S, Nicolas E, Dorchies E, Bantubungi K. Farnesoid X receptor activation in brain alters brown adipose tissue function via the sympathetic system. Front Mol Neurosci 2022; 14: 808603.
• Duan H, Xiao L, Hu J, Zhang Y, Zhao X, Ge W, Luo W. Expression of oestrogen receptor, androgen receptor and progesterone nuclear receptor in sheep uterus during the oestrous cycle. Reprod Dom Anim 2019; 54: 1305-12.
• Eraslan G, Soyer Sarıca Z, Çakır Bayram L, Tekeli MY, Kanbur M, Karabacak M. The effects of diosmin on aflatoxin-induced liver and kidney damage. Environ Sci Pollut Res 2017; 24(36): 27931-41.
• Friedman SL. Molecular mechanisms of hepatic fibrosis and principles of therapy. J Gastroente- rol,1997;32:424-430.
• Friedman SL. Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J Biol Chem, 2000;275:2247-2250.
• Froment P, Fabre S, Dupont J, Pisselet C, Chesneau D, Staels B, Monget P. Expression and functional role of peroxisome proliferator-activated receptor-γ in ovarian folliculogenesis in the sheep. Biol Rep- rod 2003; 69(5): 1665-74.
• Gonzales FJ, Yu AM. Cytochrome P450 and xenobiotic receptor humanized mice. Annu Rev Pharma- col Toxicol 2006; 46: 41-64.
• Greger DL, Gropp F, Morel C, Sauter S, Blum JW. Nuclear receptor and target gene mRNA abundance in duodenum and colon of dogs with chronic enteropathies. Domest Anim Endocrinol 2006b; 31 (4): 327-39.
• Greger DL, Philipona C, Blum JW. Ontogeny of mRNA abundance of nuclear receptors and nuclear receptor target genes in young cattle. Domest Anim Endocrinol 2006a; 31(1): 76-87.
• Han SY, Song HK, Cha JJ, Han JY, Kang YS, Cha DR. Farnesoid X receptor (FXR) agonist ameliorates systemic insulin resistance, dysregulation of lipid metabolism, and alterations of various organs in a type 2 diabetic kidney animal model. Acta Dia- betol 2021; 58(4): 495-503.
• Harmancı Ö, Dağlı Ü. İnflamatuvar bağırsak hastalı- ğında kolorektal kanser. Güncel Gastroenteroloji 2013; 17(4): 321-4.
• Huss JM, Kelly DP. Nuclear receptor signaling and cardiac energetics. Circ Res 2004; 95(6): 568-78.
• Jameson JL. Endokrinolojinin esasları. Fauci AS. Kasper DL. Longo DL. Braunwalt E. Hauser SL. Jameson JL. Loscalzo J. İn: Harison endokrinoloji. Çeviren Akçay T (İstanbul: Nobel Matbacılık, 2013) pp. 1-45
• Kanbur M, Siliğ Y, Eraslan G, Karabacak M, Soyer Sarıca Z, Şahin S. The toxic effect of cypermethrin, amitraz and combinations of cypermethrin-amitraz in rats. Environ Sci Pollut Res 2016; 23(6): 5232- 42.
• Kaya S. İlaçların etki şekilleri ve etkileri. Kaya S. Eds. İn: Veteriner Farmakoloji. Beşinci Baskı. Ankara: Medisan Yayınları, 2009; ss. 89-117.
• Keong KGS. The role of peroxisome proliferator activated receptor (PPAR) isoforms in the pathogenesis of type 1 diabetes in male non-obese diabetıc (nod) mice, Master's thesis, USM 2008; s. 110.
• Labinskyy V, Bellomo M, Chandler MP, Young ME, Lionetti V, Qanud K, Recchia FA. Chronic activation of PPAR {alpha} with fenofibrate prevents alterations in cardiac metabolic phenotype without changing the onset of decompensation in pacing- induced heart failure. J Pharmacol Exp Ther 2007; 321(1): 165-71.
• Lazarević S, Đanić M, Goločorbin-Kon S, Al-Salami H, Mikov M. Semisynthetic bile acids: A new therapeutic option for metabolic syndrome. Pharmacol res 2019; 146: 104333.
• Maeda A, Horikoshi S, Gohda T et al. Pioglitazone attenuates TGF-beta(1)-induction of fibronectin synthesis and its splicing variant in human mesangial cells via activation of peroxisome proliferator- activated receptor (PPAR)gamma. Cell Biol Int. 2005; 29(6):422-8.
• Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schütz G. The nuclear receptor superfamily: The second decade. Cell 1995; 83: 835-9.
• McEvan JI. The nuclear receptor superfamily. First Edition. New York: Humana Press, 2009; pp. 1-18.
• Moore JT, Collins JL, Pearce KH. The nuclear receptor superfamily and drug discovery. Chem Med Chem 2006; 1(5): 504-23.
• Nebbia C. Biotransformation enzymes as determinants of xenobiotic toxicity in domestic animals. Vet J 2001; 161(3): 238-52.
• Ottow E, Weinman H. Nuclear receptors as drug tragets. Volume 39. Weinheim, Germany: Wiley-Vch, 2008; p.1-382.
• Plant N, Aouabdi S. Nuclear receptors: the controlling force in drug metabolism of the liver. Xenobiotica 2009; 39(8): 597-605.
• Ribeiro ES. Symposium review: Lipids as regulators of conceptus development: Implications for metabolic regulation of reproduction in dairy cattle. J Dairy Sci 2018; 101(4): 3630-3641.
• Sağlam F. Peroksizom proliferatör aktive reseptör-γ agonisti pioglitazon’un enkapsüle peritoneal fibrozis modelinde periton membranı üzerine olan etkileri, Uzmanlık tezi, Dokuz Eylül Üniv Tıp Fakültesi, İz- mir, 2009; s. 46.
• Seydel GŞ. Hepatosellüler karsinomaya neden olan genlerin gen ekspresyonunun kantitatif ölçümü, Doktora tezi, Çukurova Üniv Sağ Bil Ens, Adana, 2011; s. 110.
• Squires EJ, Sueyoshi T, Negishi M. Cytoplasmic localization of pregnane X receptor and ligand- dependent nuclear translocation in mouse liver. J Biol Chem 2004; 279 (47): 49307-14.
• Süzer Ö. Farmakodinamik: İlaçların etki mekanizma- ları, toksik etkileri, doz yanıt ilişkisi. Klinik Gelişim 2008; 21(2): 33-41.
• Şenol ŞP, Tunçtan B. Peroksizom proliferatör ile et- kinleştirilen reseptörlerin insülin direnci ve septik şok patojenezindeki rolü. MÜSBED 2015; 5(4): 247 -58.
• Tardelli M, Claudel T, Bruschi FV, Trauner M. Nuclear receptor regulation of aquaglyceroporins in metabolic organs. Int J Mol Sci 2018; 19(6): 1777.
• Usman A, Gürçelik NE. Novel therapeutic approaches in cushing’s disease: PPAR-gamma agonists, Turk J Endocrinol Metab 2009; 13(4): 80-83.
• Ünal AD, Ünal HÜ. Glukoz metabolizmasında yeni oyuncu: safra asitleri. Güncel Gastroenteroloji 2011, 15 (4): 254-6.
• Weikum ER, Liu X, Ortlund EA. The nuclear receptor superfamily: A structural perspective. Protein Sci 2018; 27(11), 1876-92.
• Xie W, Barwick JL, Downes M. Humanized xenobiotic response in mice expressing nuclear receptor sxr. Nature 2000; 406: 435-8.
• Yan J, Chen B, Lu J, Xie W. Deciphering the roles of the constitutive androstane receptor in energy metabolism. Acta Pharmacol Sin 2015; 36: 62-70.