کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2514487 1118469 2009 19 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The significance of the nongenomic pathway in mediating inflammatory signaling of the dioxin-activated Ah receptor to cause toxic effects
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
پیش نمایش صفحه اول مقاله
The significance of the nongenomic pathway in mediating inflammatory signaling of the dioxin-activated Ah receptor to cause toxic effects
چکیده انگلیسی

Evidence has been accumulating to indicate that the current classical model of dioxin's action based on the ligand-activated aryl hydrocarbon receptor (AHR) and AHR nuclear translocator (ARNT) dimer directly activating its target genes is not robust enough to explain many of the major toxic effects of this compound. In this review, efforts have been made to analyze the results of recent investigations in our laboratory in comparison to already existing evidence on the patterns of toxic actions of dioxin (=TCDD) from other laboratories from a specific viewpoint of elicitation of cellular inflammatory signaling by the ligand-activated AHR. The most salient features of the inflammatory action of TCDD are that its triggering events, such as the rapid increase in intracellular Ca2+ concentration, enzymatic activation of cytosolic phospholipase A2 (cPLA2) and that of Cox-2 are taking place through the nongenomic action of the ligand-activated AHR. This nongenomic pathway does not require ARNT. Therefore, this inflammation pathway is clearly discernable from the classical, genomic action pathway. The effect of such a nongenomic signaling persists for long time periods as shown by recent findings that artificial suppression of the early triggering events of this pathway, such as via suppression of cPLA2, Cox-2, or Src kinase indeed causes significant reduction of manifestations of hallmark toxicities of TCDD such as wasting syndrome and hydronephrosis. Together, the evidence strongly support the notion that the inflammatory action of the ligand-activated AHR that is mediated by the nongenomic pathway plays the major role in the inflammation inducing actions of dioxin-like chemicals.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 77, Issue 4, 15 February 2009, Pages 608–626
نویسندگان
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