کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2601623 1133335 2006 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Involvement of endoplasmic reticulum in glycochenodeoxycholic acid-induced apoptosis in rat hepatocytes
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Involvement of endoplasmic reticulum in glycochenodeoxycholic acid-induced apoptosis in rat hepatocytes
چکیده انگلیسی

In chronic cholestatic liver diseases, accumulation of hydrophobic bile acids is thought to damage hepatocytes. The mechanism of how cells die has been an open debate, but apoptotic pathways are known to involve activation of death receptors and mitochondrial dysfunction. Recently apoptosis via an endoplasmic reticulum (ER) stress-mediated pathway was also found. In this study, we examined whether ER stress is induced in rat hepatocytes by treatment with glycochenodeoxycholic acid (GCDCA, 50–300 μM for 1–24 h), and if so, whether ER stress-mediated apoptosis occurs in this system. We determined mobility of intracellular calcium ion, activities of calpain and caspase-12, specific to ER stress-mediated apoptosis, and Bip and Chop mRNA expressions, biomarkers of ER stress. We found that GCDCA induces ER-related calcium release within about ten seconds. Significant increases in activities of calpain and caspase-12 were observed after 15 h of GCDCA treatment. Bip and Chop mRNA expressions were increased with the treated GCDCA dose and incubation time. Cytochrome c release from mitochondria peaked in about 2 h of incubation. These results suggest that ER stress is actually induced by GCDCA, though its role in hepatocellular apoptosis may be smaller than mitochondria-mediated pathway. The presence of ER stress might be important in pathogenesis of cholestatic liver diseases.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 166, Issue 2, 10 October 2006, Pages 140–149
نویسندگان
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