کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1940533 | 1050783 | 2006 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: The human transcription factor AP-1 is a mediator of bile acid-induced liver cell apoptosis The human transcription factor AP-1 is a mediator of bile acid-induced liver cell apoptosis](/preview/png/1940533.png)
Apoptosis induced by toxic bile acids is thought to contribute to liver injury during cholestasis. The transcription factor AP-1 is involved in the induction of apoptosis depending on stimulus and cell type. It is not known whether the major human toxic bile acid, glycochenodeoxycholic acid (GCDCA), modulates AP-1 in hepatocytes. Our data show that GCDCA (75 μM, 4 h) significantly upregulates cFos and JunB as demonstrated by microarray analysis and real-time PCR in HepG2-Ntcp hepatoma cells. GCDCA (75 μM, 4 h) also induced AP-1 activation as determined by EMSA that was most distinct after 30 min. In parallel, AP-1 transcriptional activity increased by 40% after exposure to GCDCA. Curcumin, an AP-1 inhibitor, dose-dependently reduced (1–25 μM) or completely abolished (50 μM) the apoptotic effect of GCDCA. Thus, GCDCA-induced upregulation of AP-1-dependent genes appears important for the cytotoxicity of this bile acid.
Journal: Biochemical and Biophysical Research Communications - Volume 340, Issue 3, 17 February 2006, Pages 800–806