کد مقاله کد نشریه سال انتشار مقاله انگلیسی ترجمه فارسی نسخه تمام متن
5509397 1538513 2017 41 صفحه PDF سفارش دهید دانلود رایگان
عنوان انگلیسی مقاله ISI
Cisplatin-induced necroptosis in TNFα dependent and independent pathways
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موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Cisplatin-induced necroptosis in TNFα dependent and independent pathways
چکیده انگلیسی
Cisplatin is a chemotherapeutic drug for treatment of many solid tumors. It has been shown to induce apoptosis and/or necrosis in different types of cancer cells. However, the underlying mechanisms remain elusive. In this study, we provide evidences that cisplatin induces necroptosis in receptor-interacting protein 3 (RIP3)-expressing cell lines, but not in cell lines lacking RIP3 protein expression. Deficiency of core components of necroptotic pathway, RIP1, RIP3, or mixed lineage kinase domain-like protein (MLKL) blocked cisplatin-induced cell death in L929 cells. This phenomenon is dependent on RIP1/RIP3/MLKL necrosome formation and translocation to mitochondria-associated membrane (MAM), but only partially via autocrine production of tumor necrosis factor α (TNFα). Moreover, we demonstrate that the mitochondrial permeability transition pore opening (mPTP) opening and reactive oxygen species (ROS) generation is a critical downstream event of the formation of necrosome in cisplatin-induced necroptosis, which is TNFα independent. Deficiency of cyclophilin-D (CypD) partially reduced cisplatin-induced cell death, indicating CypD mediated-mPTP opening plays an important role during cisplatin-induced necroptosis. Both deletion of CypD and TNFα completely blocked cisplatin-induced cell death, suggesting that cisplatin could induce necroptosis through TNFα dependent and independent pathway. These findings provide new insight into the molecular mechanisms underlying cisplatin-induced necroptosis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 31, February 2017, Pages 112-123
نویسندگان
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