کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9245187 | 1209942 | 2005 | 16 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Bid Is Upstream of Lysosome-Mediated Caspase 2 Activation in Tumor Necrosis Factor α-Induced Hepatocyte Apoptosis
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
EGTADAPIACDTNF-R1TNF4′,6-diamidino-2-phenylindole - 4 '، 6-دیامیدینو-2-فنیلینولBSA - BSASmall interfering RNA - RNA تداخل کوچکsiRNA - siRNAbovine serum albumin - آلبومین سرم گاوethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid - اتیلن گلیکول بیس (β-آمینویل اتر) -N، N، N '، N'-tetraacetic اسیدactinomycin D - اکتینومایسین Dtruncated Bid - تضعیف مزایدهtumor necrosis factor - فاکتور نکروز تومورwild-type - نوع وحشیtumor necrosis factor receptor 1 - گیرنده فاکتور نکروز تومور 1
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای گوارشی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Background & Aims: During tumor necrosis factor α-mediated hepatocyte cytotoxicity, cathepsin B is released from lysosomes and contributes to apoptosis by indirectly promoting mitochondrial dysfunction. How this lysosomal pathway mediates mitochondrial dysfunction is unclear. Because Bcl-2 family proteins and caspase 2 have been implicated in proximal apoptosis-signaling pathways, we examined the role of these proteins in tumor necrosis factor α-induced lysosomal permeabilization and cathepsin B-mediated mitochondrial dysfunction. Methods: Studies were performed in primary hepatocytes from wild-type cathepsin B knockout, Bid knockout, and caspase 2 knockout mice and in the rat hepatoma cell line McArdle7777 by using tumor necrosis factor α/actinomycin D. Results: Studies in wild-type and Bid knockout hepatocytes showed that tumor necrosis factor α-mediated lysosomal permeabilization is Bid dependent. After tumor necrosis factor α/actinomycin D treatment, caspase 2 activity increased severalfold in wild-type hepatocytes, whereas minimal activity was observed in hepatocytes from cathepsin B knockout mice or in hepatoma cells treated with a cathepsin B inhibitor. In contrast, Bax was activated independently of cathepsin B. Pharmacological, genetic, or small interfering RNA-mediated inhibition of caspase 2 attenuated tumor necrosis factor α-mediated mitochondrial dysfunction, downstream caspase activation, and hepatocyte apoptosis. Conclusions: These data suggest that tumor necrosis factor α triggers Bid-dependent lysosomal permeabilization, followed by release of cathepsin B into the cytosol and activation of caspase 2. Caspase 2 then facilitates efficient mitochondrial cytochrome c release and apoptosis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 129, Issue 1, July 2005, Pages 269-284
Journal: Gastroenterology - Volume 129, Issue 1, July 2005, Pages 269-284
نویسندگان
M. Eugenia Guicciardi, Steven F. Bronk, Nathan W. Werneburg, Xiao-Ming Yin, Gregory J. Gores,