کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10815972 1058534 2007 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Granzyme B induction signalling pathway in acute myeloid leukemia cell lines stimulated by Tumor Necrosis Factor alpha and Fas Ligand
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Granzyme B induction signalling pathway in acute myeloid leukemia cell lines stimulated by Tumor Necrosis Factor alpha and Fas Ligand
چکیده انگلیسی
Acute myeloid leukemia (AML) cell lines treated by genotoxic agents or by Tumor Necrosis Factor alpha (TNFα) acquire potent cytotoxicity towards myeloid cells through activation of granzyme B (GrB)/perforin (PFN) system. Here we first extend this observation to another death receptor activator, Fas Ligand (FasL). Moreover, we analyzed GrB induction signalling pathway in TNFα- and FasL-stimulated AML cells. The effects of TNFα and FasL on GrB expression were specifically mediated by p38MAPK (Mitogen-activated-protein-kinase) activation. Otherwise, TNFα and FasL stimulation led to radical oxygen species (ROS) generation and ASK1 (Apoptosis-signal-regulating-kinase-1) activation. Endogenous activation of ASK1 by either H2O2 or thioredoxin (Trx) reductase inhibition had the same effects as TNFα and FasL on GrB up regulation. Altogether, our results suggest that TNFα- and FasL-stimulated AML cell lytic induction is regulated by a signalling pathway involving sequentially, ROS generation, Trx oxidation, ASK1 activation, p38MAPK stimulation and GrB induction at mRNA and protein levels.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 19, Issue 6, June 2007, Pages 1132-1140
نویسندگان
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