کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9401376 1288263 2005 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Fas/FasL Play a Central Role in Pancreatitis-Induced Hepatocyte Apoptosis
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی عمل جراحی
پیش نمایش صفحه اول مقاله
Fas/FasL Play a Central Role in Pancreatitis-Induced Hepatocyte Apoptosis
چکیده انگلیسی
Liver injury is a clinical prognostic indicator in acute pancreatitis (AP). We have demonstrated that Kupffer cell-derived FasL mediates liver injury during AP and sought to determine its role in AP-induced hepatocyte apoptosis. AP was induced in National Institutes of Health (NIH) Swiss mice, C57/C57, and Fas-/-, FasL-/- mice by a choline-deficient ethionine-supplement diet. Liver Fas, FasL, p38-mitogen activated phosphokinase (p38-MAPK), poly-ADP ribose polymerase (PARP), and cytochrome C were measured by immunoblotting. Apoptosis was assessed by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) and DNA fragmentation (ELISA). AP upregulated liver FasL (4280 ± 580 vs. 733 ± 336), Fas (2866 ± 595 vs. 649 ± 111), cytochrome C (6980 ± 237 vs. 903 ± 156), and PARP (6393 ± 591 vs. 466 ± 261) as well as increased TUNEL staining (40 ± 2 vs. 14 ± 1) and DNA fragmentation (all P < 0.03 vs. control). In FasL-/- and Fas-/- mice, AP-induced upregulation of p38-MAPK, PARP, and cytochrome C was significantly attenuated (all P < 0.01 compared to C57/C57 control). In addition, AP-induced DNA fragmentation was reduced 60% in Fas-/- and FasL-/- mice (P < 0.01 vs. C57/C57). AP induces apoptosis by transcriptional activation of Fas/FasL. AP-induced apoptosis was significantly reduced in Fas and FasL knockout mice along with downregulation of p38-MAPK, PARP, and cytochrome C, thereby suggesting a central role for Fas/FasL in hepatocyte apoptosis. The manipulation of interactions between Kupffer cell-derived FasL and hepatocytes may have important therapeutic implications.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Gastrointestinal Surgery - Volume 9, Issue 4, 1 April 2005, Pages 467-475
نویسندگان
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