کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3315525 1211268 2007 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Hyperthyroidism induces apoptosis in rat liver through activation of death receptor-mediated pathways
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های گوارشی
پیش نمایش صفحه اول مقاله
Hyperthyroidism induces apoptosis in rat liver through activation of death receptor-mediated pathways
چکیده انگلیسی

Background/AimsThe molecular basis of hepatic dysfunction in thyrotoxicosis is not fully understood. Here, we investigated the effect of altered thyroidal status on death receptor pathways including p75 neurotrophin receptor (p75NTR), a member of tumor necrosis factor (TNF) receptor superfamily, in rat liver.MethodsHyperthyroidism was induced in Sprague–Dawley rats by daily injections of triiodothyronine in a dose of 12.5 μg/100 g body weight for 10 days.ResultsTerminal deoxynucleotide-transferase-mediated dUTP nick end labeling assay and caspase-3 activation data confirmed apoptosis in hyperthyroid rat liver. We observed the elevated levels of death ligands, TNF-α, Fas ligand and their cognate receptors, TNF-receptor-1 and Fas, and 8-fold increase in caspase-8 activation in hyperthyroid rat liver (p < 0.001). We demonstrated for the first time that hyperthyroidism elevates p75NTR levels and its ligands, pro-nerve growth factor and pro-brain-derived neurotrophic factor, in rat liver. Further we showed that most of the apoptotic cells in hyperthyroid liver express p75NTR. We also demonstrated that triiodothyronine administration to rats causes NF-κB activation, but persistent exposure (10 days) to triiodothyronine deactivates NF-κB leading to sustained c-Jun N-terminal kinase (JNK) activation.ConclusionsThis study showed that hyperthyroidism-induced apoptosis in rat liver involves the activation of death receptor-mediated pathways, including p75NTR.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Hepatology - Volume 46, Issue 5, May 2007, Pages 888–898
نویسندگان
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