Genomes and Genes
Summary: A bile salt formed in the liver by conjugation of chenodeoxycholate with taurine, usually as the sodium salt. It acts as detergent to solubilize fats in the small intestine and is itself absorbed. It is used as a cholagogue and choleretic.
- Keene C, Rodrigues C, Eich T, Linehan Stieers C, Abt A, Kren B, et al. A bile acid protects against motor and cognitive deficits and reduces striatal degeneration in the 3-nitropropionic acid model of Huntington's disease. Exp Neurol. 2001;171:351-60 pubmed..This is the first demonstration, however, that a bile acid can be delivered to the brain and function as a neuroprotectant and thus may offer potential therapeutic benefit in the treatment of certain neurodegenerative diseases. ..
- Colak A, Kelten B, Sağmanligil A, Akdemir O, Karaoglan A, Sahan E, et al. Tauroursodeoxycholic acid and secondary damage after spinal cord injury in rats. J Clin Neurosci. 2008;15:665-71 pubmed publisher..A therapeutic strategy using TUDCA may eventually lead to effective treatment of SCI without toxic effects in humans. ..
- Gregor M, Hotamisligil G. Thematic review series: Adipocyte Biology. Adipocyte stress: the endoplasmic reticulum and metabolic disease. J Lipid Res. 2007;48:1905-14 pubmed..This review will focus on the function of the ER under normal conditions in the adipocyte and the pathological effects of a stressed ER contributing to adipocyte dysfunction and a thwarted metabolic homeostasis. ..
- Lamireau T, Zoltowska M, Levy E, Yousef I, Rosenbaum J, Tuchweber B, et al. Effects of bile acids on biliary epithelial cells: proliferation, cytotoxicity, and cytokine secretion. Life Sci. 2003;72:1401-11 pubmed..Furthermore, TC, a major biliary acid in human bile, stimulated secretion of cytokines involved in the inflammatory and fibrotic processes occurring during cholestatic liver diseases. ..
- Galán M, Kassan M, Choi S, Partyka M, Trebak M, Henrion D, et al. A novel role for epidermal growth factor receptor tyrosine kinase and its downstream endoplasmic reticulum stress in cardiac damage and microvascular dysfunction in type 1 diabetes mellitus. Hypertension. 2012;60:71-80 pubmed publisher..This study unveiled novel roles for enhanced EGFRtk phosphorylation and its downstream ER stress in cardiac fibrosis and microvascular endothelial dysfunction in type 1 diabetes mellitus. ..
- Falasca L, Tisone G, Palmieri G, Anselmo A, Di Paolo D, Baiocchi L, et al. Protective role of tauroursodeoxycholate during harvesting and cold storage of human liver: a pilot study in transplant recipients. Transplantation. 2001;71:1268-76 pubmed..The use of TUDCA during harvesting and cold storage of human liver is associated with significant protection from ischemia-reperfusion injury. The clinical significance of this findings must be studied. ..
- Ramalho R, Borralho P, Castro R, Sola S, Steer C, Rodrigues C. Tauroursodeoxycholic acid modulates p53-mediated apoptosis in Alzheimer's disease mutant neuroblastoma cells. J Neurochem. 2006;98:1610-8 pubmed..In conclusion, FAD mutations are associated with the activation of classical apoptotic pathways. TUDCA reduces p53-induced apoptosis and modulates expression of Bcl-2 family. ..
- Malo A, Kruger B, Seyhun E, Schafer C, Hoffmann R, Goke B, et al. Tauroursodeoxycholic acid reduces endoplasmic reticulum stress, trypsin activation, and acinar cell apoptosis while increasing secretion in rat pancreatic acini. Am J Physiol Gastrointest Liver Physiol. 2010;299:G877-86 pubmed publisher..These data hint new perspectives for an employment of chemical chaperones in the therapy of acute pancreatitis. ..
- Zhou L, Zhang J, Fang Q, Liu M, Liu X, Jia W, et al. Autophagy-mediated insulin receptor down-regulation contributes to endoplasmic reticulum stress-induced insulin resistance. Mol Pharmacol. 2009;76:596-603 pubmed publisher..Our results uncover a new mechanism underlying obesity-induced insulin resistance and shed light on potential targets for the prevention and treatment of obesity-induced insulin resistance and type 2 diabetes. ..
- Chen Y, Liu C, Xu K, Mao X, Lu Y, Fang L, et al. Effect of taurine-conjugated ursodeoxycholic acid on endoplasmic reticulum stress and apoptosis induced by advanced glycation end products in cultured mouse podocytes. Am J Nephrol. 2008;28:1014-22 pubmed publisher..This novel mechanism of TUDCA action suggests new intervention methods for AGEs-induced apoptosis of mouse podocytes in diabetic nephropathy. ..
- Ozcan U, Yilmaz E, Ozcan L, Furuhashi M, Vaillancourt E, Smith R, et al. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science. 2006;313:1137-40 pubmed..Our results demonstrate that chemical chaperones enhance the adaptive capacity of the ER and act as potent antidiabetic modalities with potential application in the treatment of type 2 diabetes. ..
- Oveson B, Iwase T, Hackett S, Lee S, Usui S, Sedlak T, et al. Constituents of bile, bilirubin and TUDCA, protect against oxidative stress-induced retinal degeneration. J Neurochem. 2011;116:144-53 pubmed publisher..If proof-of-concept is established, manipulation of bilirubin levels and administration of TUDCA could be tested in interventional trials...
- Schoemaker M, Conde de la Rosa L, Buist Homan M, Vrenken T, Havinga R, Poelstra K, et al. Tauroursodeoxycholic acid protects rat hepatocytes from bile acid-induced apoptosis via activation of survival pathways. Hepatology. 2004;39:1563-73 pubmed..In conclusion, TUDCA contributes to the protection against GCDCA-induced mitochondria-controlled apoptosis by activating survival pathways. ..
- Colell A, Coll O, Garcia Ruiz C, Paris R, Tiribelli C, Kaplowitz N, et al. Tauroursodeoxycholic acid protects hepatocytes from ethanol-fed rats against tumor necrosis factor-induced cell death by replenishing mitochondrial glutathione. Hepatology. 2001;34:964-71 pubmed..Thus, these findings reveal a novel role of TUDCA in protecting hepatocytes in long-term ethanol-fed rats through modulation of mitochondrial membrane fluidity and subsequent normalization of mitochondrial GSH levels. ..
- Duan W, Rodrigues C, Zhao L, Steer C, Low W, Rodrigures C. Tauroursodeoxycholic acid improves the survival and function of nigral transplants in a rat model of Parkinson's disease. Cell Transplant. 2002;11:195-205 pubmed..These data demonstrate that pretreatment of the cell suspension with TUDCA can reduce apoptosis and increase the survival of grafted cells, resulting in an improvement of behavioral recovery. ..
- Wei H, Kim S, Zhang Z, Tsai P, Wisniewski K, Mukherjee A. ER and oxidative stresses are common mediators of apoptosis in both neurodegenerative and non-neurodegenerative lysosomal storage disorders and are alleviated by chemical chaperones. Hum Mol Genet. 2008;17:469-77 pubmed
- Ceylan Isik A, Sreejayan N, Ren J. Endoplasmic reticulum chaperon tauroursodeoxycholic acid alleviates obesity-induced myocardial contractile dysfunction. J Mol Cell Cardiol. 2011;50:107-16 pubmed publisher..In summary, these data depicted a pivotal role of ER stress in obesity-associated cardiac contractile dysfunction, suggesting the therapeutic potential of ER stress as a target in the management of cardiac dysfunction in obesity. ..
- Azzaroli F, Mehal W, Soroka C, Wang L, Lee J, Crispe I, et al. Ursodeoxycholic acid diminishes Fas-ligand-induced apoptosis in mouse hepatocytes. Hepatology. 2002;36:49-54 pubmed..This protective effect is not associated with reductions in Fas trimerization, but may be related to a direct effect on the mitochondrial membrane. ..
- Miller S, Greene C, McLean C, Lawless M, Taggart C, O Neill S, et al. Tauroursodeoxycholic acid inhibits apoptosis induced by Z alpha-1 antitrypsin via inhibition of Bad. Hepatology. 2007;46:496-503 pubmed..These data show that caspase-4 is not essential for ZAAT-induced apoptosis in HEK293 cells and implicates P-I-3-kinase and Bad as potential therapeutic targets for the liver disease associated with ZAAT deficiency. ..
- Phillips M, Walker T, Choi H, Faulkner A, Kim M, Sidney S, et al. Tauroursodeoxycholic acid preservation of photoreceptor structure and function in the rd10 mouse through postnatal day 30. Invest Ophthalmol Vis Sci. 2008;49:2148-55 pubmed publisher..At P30, a developmental stage at which nearly all rods are absent in the rd10 mouse model of RP, TUDCA treatment preserved rod and cone function and greatly preserved overall photoreceptor numbers. ..
- Xie Q, Khaoustov V, Chung C, Sohn J, Krishnan B, Lewis D, et al. Effect of tauroursodeoxycholic acid on endoplasmic reticulum stress-induced caspase-12 activation. Hepatology. 2002;36:592-601 pubmed..This novel mechanism of TUDCA action suggests new intervention methods for ER stress-induced liver disease. ..
- Heubi J, Wiechmann D, Creutzinger V, Setchell K, Squires R, Couser R, et al. Tauroursodeoxycholic acid (TUDCA) in the prevention of total parenteral nutrition-associated liver disease. J Pediatr. 2002;141:237-42 pubmed..Erratic biliary enrichment and prolonged inability to initiate treatment may compromise the utility of enterically administered TUDCA for TPN-treated infants. ..
- Rodrigues C, Sola S, Nan Z, Castro R, Ribeiro P, Low W, et al. Tauroursodeoxycholic acid reduces apoptosis and protects against neurological injury after acute hemorrhagic stroke in rats. Proc Natl Acad Sci U S A. 2003;100:6087-92 pubmed..Thus, given its clinical safety, TUDCA may provide a potentially useful treatment in patients with hemorrhagic stroke and perhaps other acute brain injuries associated with cell death by apoptosis. ..
- Cardoso I, Martins D, Ribeiro T, Merlini G, Saraiva M. Synergy of combined doxycycline/TUDCA treatment in lowering Transthyretin deposition and associated biomarkers: studies in FAP mouse models. J Transl Med. 2010;8:74 pubmed publisher..The observed synergistic effect of doxycycline/TUDCA in the range of human tolerable quantities, in the transgenic TTR mice models prompts their application in FAP, particularly in the early stages of disease. ..
- Nathanson M, Burgstahler A, Masyuk A, LaRusso N. Stimulation of ATP secretion in the liver by therapeutic bile acids. Biochem J. 2001;358:1-5 pubmed..This strategy may be useful for treatment of cystic fibrosis and other secretory disorders of the liver and other epithelial tissues. ..
- Rodrigues C, Spellman S, Sola S, Grande A, Linehan Stieers C, Low W, et al. Neuroprotection by a bile acid in an acute stroke model in the rat. J Cereb Blood Flow Metab. 2002;22:463-71 pubmed..Thus, TUDCA, a clinically safe molecule, may be useful in the treatment of stroke and possibly other apoptosis-associated acute and chronic injuries to the brain. ..
- Lee Y, Hong S, Lee Y, Chung S, Jung H, Park S, et al. Tauroursodeoxycholate (TUDCA), chemical chaperone, enhances function of islets by reducing ER stress. Biochem Biophys Res Commun. 2010;397:735-9 pubmed publisher..42+/-0.15 vs. 1.92+/-0.12, n=12, p<0.05). Taken together, we suggest that TUDCA could be a useful agent for islet protection in islet isolation for transplantation. ..
- Sola S, Castro R, Laires P, Steer C, Rodrigues C. Tauroursodeoxycholic acid prevents amyloid-beta peptide-induced neuronal death via a phosphatidylinositol 3-kinase-dependent signaling pathway. Mol Med. 2003;9:226-34 pubmed..Together, these findings indicate that Abeta-induced apoptosis of cortical neurons proceeds through a Bax mitochondrial pathway. Further, the PI3K signaling cascade plays a role in regulating the anti-apoptotic effects of TUDCA. ..
- Kurz A, Graf D, Schmitt M, Vom Dahl S, Haussinger D. Tauroursodesoxycholate-induced choleresis involves p38(MAPK) activation and translocation of the bile salt export pump in rats. Gastroenterology. 2001;121:407-19 pubmed..Dual activation of Erks and p38(MAPK) is required for the choleretic effect of both TUDC and hypo-osmotic cell swelling. ..
- Dromparis P, Paulin R, Stenson T, Haromy A, Sutendra G, Michelakis E. Attenuating endoplasmic reticulum stress as a novel therapeutic strategy in pulmonary hypertension. Circulation. 2013;127:115-25 pubmed publisher..Attenuating ER stress with clinically used chemical chaperones may be a novel therapeutic strategy in pulmonary hypertension with high translational potential. ..
- Rivard A, Steer C, Kren B, Rodrigues C, Castro R, Bianco R, et al. Administration of tauroursodeoxycholic acid (TUDCA) reduces apoptosis following myocardial infarction in rat. Am J Chin Med. 2007;35:279-95 pubmed..Additional studies will distinguish the functional result of improved cell survival following infarction, suggesting the potential for clinical application of this anti-apoptotic drug in treatment of acute MI. ..
- Araya Z, Wikvall K. 6alpha-hydroxylation of taurochenodeoxycholic acid and lithocholic acid by CYP3A4 in human liver microsomes. Biochim Biophys Acta. 1999;1438:47-54 pubmed..from different donors, and selective cytochrome P450 inhibitors were used to study the hydroxylation of taurochenodeoxycholic acid and lithocholic acid...
- Invernizzi P, Setchell K, Crosignani A, Battezzati P, Larghi A, O Connell N, et al. Differences in the metabolism and disposition of ursodeoxycholic acid and of its taurine-conjugated species in patients with primary biliary cirrhosis. Hepatology. 1999;29:320-7 pubmed..This comparative study suggests that tauroursodeoxycholate has significant advantages over ursodeoxycholate that may be of benefit for long-term therapy in PBC. ..
- Ozcan L, Ergin A, Lu A, Chung J, Sarkar S, Nie D, et al. Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metab. 2009;9:35-51 pubmed publisher..Taken together, our results may provide the basis for a novel treatment of obesity...
- Kars M, Yang L, Gregor M, Mohammed B, Pietka T, Finck B, et al. Tauroursodeoxycholic Acid may improve liver and muscle but not adipose tissue insulin sensitivity in obese men and women. Diabetes. 2010;59:1899-905 pubmed publisher..These data demonstrate that TUDCA might be an effective pharmacological approach for treating insulin resistance. Additional studies are needed to evaluate the target cells and mechanisms responsible for this effect. ..
- Rust C, Bauchmuller K, Fickert P, Fuchsbichler A, Beuers U. Phosphatidylinositol 3-kinase-dependent signaling modulates taurochenodeoxycholic acid-induced liver injury and cholestasis in perfused rat livers. Am J Physiol Gastrointest Liver Physiol. 2005;289:G88-94 pubmedb>Taurochenodeoxycholic acid (TCDCA), but not glycochenodeoxycholic acid (GCDCA), activates a phosphatidylinositol 3-kinase (PI3-K)-mediated survival pathway in vitro...
- Jiao P, Ma J, Feng B, Zhang H, Diehl J, Chin Y, et al. FFA-induced adipocyte inflammation and insulin resistance: involvement of ER stress and IKK? pathways. Obesity (Silver Spring). 2011;19:483-91 pubmed publisher..These results indicate that ER stress pathway is a key mediator for FFA-induced inflammation and insulin resistance in adipocytes with PERK and IKK? as the critical signaling components. ..
- Younce C, Kolattukudy P. MCP-1 induced protein promotes adipogenesis via oxidative stress, endoplasmic reticulum stress and autophagy. Cell Physiol Biochem. 2012;30:307-20 pubmed publisher..Preadipocytes in adipogenesis-inducing cocktail manifested ER stress and autophagy. Knockdown of MCPIP attenuated these effects. MCPIP induced p38 activation and p38 inhibitor, SB203580, attenuated MCPIP-induced adipogenesis. ..
- Barth A, Braun J, Muller D. Influence of Verapamil and Cyclosporin A on bile acid metabolism and transport in rat liver slices. Exp Toxicol Pathol. 2006;58:31-7 pubmed..The similar effects of V and CsA on BA transport and metabolism can be explained by mdr1 mediated disturbances of cellular ATP transport rather than by inhibition of individual BA transporters. ..
- Omura T, Asari M, YAMAMOTO J, Oka K, Hoshina C, Maseda C, et al. Sodium tauroursodeoxycholate prevents paraquat-induced cell death by suppressing endoplasmic reticulum stress responses in human lung epithelial A549 cells. Biochem Biophys Res Commun. 2013;432:689-94 pubmed publisher..Our findings also suggest that TUDCA treatment represses the onset of pulmonary fibrosis caused by paraquat, and therefore chemical chaperones may have novel therapeutic potential for the treatment of paraquat poisoning. ..
- Chignard N, Mergey M, Veissiere D, Parc R, Capeau J, Poupon R, et al. Bile acid transport and regulating functions in the human biliary epithelium. Hepatology. 2001;33:496-503 pubmed..The differential effect of TUDC may cause a reduction in bile inspissation and provide a benefit in biliary disorders. ..
- Turdi S, Hu N, Ren J. Tauroursodeoxycholic acid mitigates high fat diet-induced cardiomyocyte contractile and intracellular Ca2+ anomalies. PLoS ONE. 2013;8:e63615 pubmed publisher..These data depict that TUDCA may ameliorate high fat diet feeding-induced cardiomyocyte contractile and intracellular Ca(2+) defects through mechanisms associated with mitochondrial integrity, AMPK, JNK and IRS-1 serine phosphorylation. ..
- Fu Y, Zhang T. Pathophysilogical mechanism and treatment strategies for Leber congenital amaurosis. Adv Exp Med Biol. 2014;801:791-6 pubmed publisher..We found that systemic injection of an ER chemical chaperone, tauroursodeoxycholic acid (TUDCA), is effective in reducing ER stress, preventing apoptosis, and preserving cones in Lrat (-/-) mice. ..
- Mantopoulos D, Murakami Y, Comander J, Thanos A, Roh M, Miller J, et al. Tauroursodeoxycholic acid (TUDCA) protects photoreceptors from cell death after experimental retinal detachment. PLoS ONE. 2011;6:e24245 pubmed publisher..TUDCA may be used as a novel therapeutic agent for preventing vision loss in diseases that are characterized by photoreceptor detachment. ..
- Ved R, Saha S, Westlund B, Perier C, Burnam L, Sluder A, et al. Similar patterns of mitochondrial vulnerability and rescue induced by genetic modification of alpha-synuclein, parkin, and DJ-1 in Caenorhabditis elegans. J Biol Chem. 2005;280:42655-42668 pubmed publisher..These results show that diverse PD-related genetic modifications disrupt the mitochondrial function in C. elegans, and they raise the possibility that mitochondrial disruption is a pathway shared in common by many types of familial PD. ..
- Beuers U. Effects of bile acids on hepatocellular signaling and secretion. Yale J Biol Med. 1997;70:341-6 pubmed..The present paper provides a brief overview of the effects of bile acids on three key messengers in liver cells: cytosolic free calcium, protein kinase A and protein kinase C. ..
- Lo A, Callaerts Vegh Z, Nunes A, Rodrigues C, D Hooge R. Tauroursodeoxycholic acid (TUDCA) supplementation prevents cognitive impairment and amyloid deposition in APP/PS1 mice. Neurobiol Dis. 2013;50:21-9 pubmed publisher..Furthermore, TUDCA-supplemented APP/PS1 mice displayed reduced hippocampal and prefrontal amyloid deposition. These effects of TUDCA supplementation suggest a novel mechanistic route for Alzheimer therapeutics. ..
- Nonaka M, Tazuma S, Hyogo H, Kanno K, Chayama K. Cytoprotective effect of tauroursodeoxycholate on hepatocyte apoptosis induced by peroxisome proliferator-activated receptor gamma ligand. J Gastroenterol Hepatol. 2008;23:e198-206 pubmed..We speculate that the administration of TUDC might be one of the potential strategies for the hepatotoxicity caused by TGZ. ..
- Wang L, Piguet A, Schmidt K, Tordjmann T, Dufour J. Activation of CREB by tauroursodeoxycholic acid protects cholangiocytes from apoptosis induced by mTOR inhibition. Hepatology. 2005;41:1241-51 pubmed..In conclusion, TUDCA activates CREB in cholangiocytes, reducing the apoptotic effect of CCI-779. These findings suggest a novel cytoprotective mechanism for this bile acid. ..
- van Nieuwerk C, Groen A, Ottenhoff R, van Wijland M, van den Bergh Weerman M, Tytgat G, et al. The role of bile salt composition in liver pathology of mdr2 (-/-) mice: differences between males and females. J Hepatol. 1997;26:138-45 pubmed..These observations support our hypothesis that liver pathology in the mdr2 (-/-) mouse is caused by bile salts and depends on the hydrophobicity c.q. cytotoxicity of biliary bile salts. ..