مورد إلكتروني
Uloga žučnih kiselina u epigenetskoj regulaciji oksidativnog stresa i apoptoze u normalnim i malignim ćelijama
| العنوان: | Uloga žučnih kiselina u epigenetskoj regulaciji oksidativnog stresa i apoptoze u normalnim i malignim ćelijama |
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| المصدر: | Универзитет у Новом Саду |
| بيانات النشر: | Универзитет у Новом Саду, Медицински факултет 2018-03-09 |
| تفاصيل مُضافة: | Stankov, Karmen Mikov, Momir Dobrić, Silva Lalić-Popović, Mladena Vasović, Velibor Goločorbin-Kon, Svetlana Pavlović, Nebojša |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Žučne kiseline deluju kao signalni molekuli u organizmu i uključene su u regulaciju brojnih metaboličkih, inflamatornih i imunomodulatornih procesa. Ova endogena jedinjenja ostvaruju svoje efekte najvećim delom putem nuklearnih receptora. Farnezoid X receptor (FXR) je glavni regulator homeostaze žučnih kiselina, a pokazano je da je značajno uključen i u procese inflamacije i kancerogeneze, prevashodno u jetri i intestinalnom traktu. Aktivacija FXR receptora predstavlja značajnu farmakološku strategiju za terapiju holestatskih bolesti jetre, inflamatorne bolesti creva i karcinoma kolona. Definisana je uloga žučnih kiselina u signalnim putevima koji regulišu ćelijski ciklus i doprinose razvoju ili regresiji maligniteta, ali je malo poznat uticaj ovih jedinjenja na epigenetske mehanizme regulacije ključnih ćelijskih procesa. Imajući u vidu da su efekti žučnih kiselina determinisani njihovom polarnošću, cilj istraživanja je bio da se ispita uticaj sintetski dobijenog keto derivata holne kiseline, 12-monoketoholne kiseline (MKH), u komparaciji sa prirodnim žučnim kiselinama, hidrofobnom henodeoksiholnom kiselinom (HDH) i hidrofilnom ursodeoksiholnom kiselinom (UDH), na ćelijske procese apoptoze, oksidativnog stresa i inflamacije, koji su od značaja za hemoprevenciju i terapiju karcinoma kolona, u in vitro i in vivo sistemima. Cilj istraživanja je takođe obuhvatao i ispitivanje uloge odabranih žučnih kiselina u epigenetskoj regulaciji ovih procesa u ćelijama karcinoma kolona. Na in vivo modelu intrahepatične holestaze kod eksperimentalnih životinja, pokazano je da UDH i MKH ispoljavaju antiapoptotski, antioksidativni i antiinflamatorni efekat u jetri i intestinumu. Utvrđeno je da UDH i MKH sprečavaju mitohondrijalni put aktivacije apoptoze u jetri, dok UDH ispoljava antiapoptotski efekat i u intestinumu eksperimentalnih životinja sa holestazom. Ove dve žučne kiseline su u značajnoj meri modulirale ekspresiju gena uključenih u antioksidativnu zaštitu, kao i aktivnost antio Bile acids act as signaling molecules in the organism and they are involved in the regulation of numerous metabolic, inflammatory and immunomodulatory processes. These endogenous compounds exert their effects mostly by binding and activation of nuclear receptors. Farnesoid X receptor (FXR) is the main regulator of bile acid homeostasis, and has been shown to be significantly involved in processes of inflammation and carcinogenesis, primarily in the liver and intestinal tract. Activation of FXR receptor represents a significant pharmacological strategy for the treatment of cholestatic liver disease, inflammatory bowel disease, and colon carcinoma. The role of bile acids in signaling pathways regulating the cell cycle and contributing to the development or regression of malignancies is well determined, but the effects of these compounds on epigenetic mechanisms of key cellular processes regulation is yet to be elucidated. Given that the effects of bile acids are mostly determined by their polarity, the aim of our study was to investigate in vitro and in vivo effects of semi-synthetic keto derivative of cholic acid, 12-monoketocholic acid (MKC), in comparison to natural bile acids, hydrophobic chenodeoxycholic acid (CDC) and hydrophilic ursodeoxycholic acid (UDC), on processes of apoptosis, oxidative stress and inflammation, which are significant for both chemoprevention and therapy of colon cancer. Besides, the aim of our study was to examine the role of selected bile acids in the epigenetic regulation of these processes in colon cancer cells. In in vivo model of intrahepatic cholestasis in experimental animals, it has been demonstrated that UDC and MKC exhibit antiapoptotic, antioxidant, and antiinflammatory effects in the liver and intestine. It was shown that UDC and MKC prevent the mitochondrial pathway of apoptosis activation in the liver, while UDC exhibits an antiapoptotic effect in the intestine of experimental animals with cholestasis as well. These two bile |
| مصطلحات الفهرس: | žučne kiseline i soli, apoptoza, antineoplastični lekovi, histon deacetilaza, epigenomika, neoplazme kolona, holestaza, inflamacija, Bile Acids and Salts, Apoptosis, Antineoplastic Agents, Histone Deacetylase, Epigenomics, Colonic Neoplasms, Cholestasis, Inflammation, doctoralThesis |
| URL: | info:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/41012/RS |
| الإتاحة: | Open access content. Open access content https://creativecommons.org/licenses/by-nc-nd/4.0 BY-NC-ND openAccess |
| أرقام أخرى: | RSPST oai:nardus.mpn.gov.rs:123456789/9274 https://www.cris.uns.ac.rs/DownloadFileServlet/Disertacija150668247669721.pdf?controlNumber=(BISIS)105058&fileName=150668247669721.pdf&id=10530&source=NaRDuS&language=sr https://www.cris.uns.ac.rs/record.jsf?recordId=105058&source=NaRDuS&language=sr https://www.cris.uns.ac.rs/DownloadFileServlet/IzvestajKomisije150668248657679.pdf?controlNumber=(BISIS)105058&fileName=150668248657679.pdf&id=10531&source=NaRDuS&language=sr https://hdl.handle.net/21.15107/rcub_nardus_9274 1242117042 |
| المصدر المساهم: | UIVERSITY OF BELGRADE From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.on1242117042 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |