کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2570361 1128581 2008 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Activation of oxidative stress-responsive signaling pathways in early splenotoxic response of aniline
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Activation of oxidative stress-responsive signaling pathways in early splenotoxic response of aniline
چکیده انگلیسی
Aniline exposure causes toxicity to the spleen, which leads to a variety of sarcomas, and fibrosis appears to be an important preneoplastic lesion. However, early molecular mechanisms in aniline-induced toxicity to the spleen are not known. Previously, we have shown that aniline exposure results in iron overload and induction of oxidative stress in the spleen, which can cause transcriptional upregulation of fibrogenic/inflammatory cytokines via activation of oxidative stress (OS)-responsive signaling pathways. To test this mechanism, male SD rats were treated with aniline (1mmol/kg/day via gavage) for 7days, an experimental condition that precedes the appearance of fibrosis. Significant increases in both NF-κB and AP-1 binding activity was observed in the nuclear extracts of splenocytes from aniline-treated rats as determined by ELISAs, and supported by Western blot data showing increases in p-IκBα, p-p65 and p-c-Jun. To understand the upstream signaling events which could account for the activation of NF-κB and AP-1, phosphorylation patterns of IκB kinases (IKKα and IKKβ) and mitogen-activated protein kinases (MAPKs) were pursued. Our data showed remarkable increases in both p-IKKα and p-IKKβ in the splenocytes from aniline-treated rats, suggesting their role in the phosphorylation of both IκBα and p65 subunits. Furthermore, aniline exposure led to activation of all three classes of MAPKs, as evident from increased phosphorylation of extracellular-signal-regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK1/2) and p38 MAPKs, which could potentially contribute to the observed activation of both AP-1 and NF-κB. Activation of upstream signaling molecules was also associated with simultaneous increases in gene transcription of cytokines IL-1, IL-6 and TNF-α. The observed sequence of events following aniline exposure could initiate a fibrogenic and/or tumorigenic response in the spleen.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 230, Issue 2, 15 July 2008, Pages 227-234
نویسندگان
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