Modulation of nuclear steroid receptors by ursodeoxycholic acid inhibits TGF-beta1-induced E2F-1/p53-mediated apoptosis of rat hepatocytes

Biochemistry
Susana SoláCecília M P Rodrigues

Abstract

We have recently shown that both ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid (TUDCA) prevent transforming growth factor beta1 (TGF-beta1)-induced hepatocyte apoptosis by modulating the E2F-1/p53/Bax pathway. In addition, activation of glucocorticoid (GR) and mineralocorticoid receptors (MR) inhibits apoptosis in various systems. UDCA induces a ligand-independent activation of the GR, thus potentially regulating a number of targets. In this study, we investigated the role of GR and MR during TGF-beta1-induced hepatocyte apoptosis, and identified additional antiapoptotic targets for UDCA. Our results showed that in primary hepatocytes, TGF-beta1 induced 40-50% decreases in gr and mr mRNA expression (p < 0.01), together with up to 10-fold reductions in their protein levels (p < 0.01). Notably, pretreatment with UDCA resulted in a significant upregulation of nuclear steroid receptors (p < 0.05), which coincided with 2- and 3-fold increases in the level of GR and MR nuclear translocation, respectively, when compared with that of TGF-beta1 alone (p < 0.05). Similarly, TUDCA induced GR and MR nuclear translocations (p < 0.05) and markedly prevented MR protein changes associated with TGF-beta1 (p < 0.05) without affecting...Continue Reading

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Citations

Jun 19, 2007·Analytical and Bioanalytical Chemistry·Benedetto NataliniRoberto Pellicciari
Apr 26, 2008·Investigative Ophthalmology & Visual Science·M Joe PhillipsMachelle T Pardue
May 7, 2009·Journal of Lipid Research·Joana D AmaralCecília M P Rodrigues
Apr 11, 2009·World Journal of Gastroenterology : WJG·Maria-J Perez, Oscar Briz
Mar 31, 2006·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Susana SoláCecília M P Rodrigues
Oct 9, 2009·Bioscience Reports·Joana D AmaralCecília M P Rodrigues
Dec 25, 2012·Biochemical Pharmacology·Joana Dias AmaralCecília Maria Pereira Rodrigues
Aug 12, 2015·World Journal of Gastrointestinal Pharmacology and Therapeutics·Elias Kouroumalis, George Notas
Apr 30, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Lifu WangJean-François Dufour
Aug 11, 2005·Journal of Biochemistry·Satoko YuiKimikazu Iwami
Sep 22, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Susana SoláCecília M P Rodrigues
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Nov 27, 2015·American Journal of Physiology. Gastrointestinal and Liver Physiology·Máté KatonaViktoria Venglovecz
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Sep 21, 2007·The Journal of Biological Chemistry·Joana D AmaralCecília M P Rodrigues
Dec 17, 2010·Journal of Medicinal Chemistry·Ruchika SharmaJohn F Gilmer

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