التفاصيل البيبلوغرافية
| العنوان: |
A fluorescent analogue of tauroursodeoxycholic acid reduces ER stress and is cytoprotective. |
| المؤلفون: |
Gavin, Jason1, Quilty, Fran1, Majer, Ferenc1, Gilsenan, Georgina1, Byrne, Anne Marie2, Long, Aideen2, Radics, Gabor1, Gilmer, John F.1 gilmerjf@tcd.ie |
| المصدر: |
Bioorganic & Medicinal Chemistry Letters. Nov2016, Vol. 26 Issue 21, p5369-5372. 4p. |
| مصطلحات موضوعية: |
*TAUROURSODEOXYCHOLIC acid, *CYTOPROTECTION, *ENDOPLASMIC reticulum, *MOLECULAR chaperones, *TAURINE |
| مستخلص: |
Tauroursodeoxycholic acid (TUDCA) is a cytoprotective ER stress inhibitor and chemical chaperone. It has therapeutic potential in a wide array of diseases but a specific macromolecular target or molecular mechanism of action remains obscure. This Letter describes an effective new synthetic approach to taurine conjugation of bile acids which we used to prepare 3α-dansyl TUDCA ( 4 ) as a probe for TUDCA actions. As a model of ER stress we used the hepatocarcinoma cell line HUH7 and stimulation with either deoxycholic acid (DCA, 200 μM) or tunicamycin (5 μg/ml) and measured levels of Bip/GRP78, ATF4, CHOP and XBP1s/XBP1u. Compound 4 was more effective than UDCA at inhibiting ER stress markers and had similar effects to TUDCA. In a model of cholestasis using the cytotoxic DCA to induce apoptosis, pretreatment with 4 prevented cell death similarly to TUDCA whereas the unconjugated clinically used UDCA had no effect. 3α-Dansyl TUDCA ( 4 ) appears to be a suitable reporter for TUDCA effects on ER stress and related cytoprotective activity. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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