کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2597157 1132568 2008 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Activation of protein kinase Cα signaling prevents cytotoxicity and mutagenicity following lead acetate in CL3 human lung cancer cells
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Activation of protein kinase Cα signaling prevents cytotoxicity and mutagenicity following lead acetate in CL3 human lung cancer cells
چکیده انگلیسی

Protein kinase C (PKC) family of serine/threonine protein kinases is sensitive signaling transducers in response to lead acetate (Pb) that could transmit phosphorylation cascade for proliferation and de-differentiation of neural cells. However, little is known as to the impact of PKC on Pb genotoxicity. Here we investigate whether Pb activates the conventional/classical subfamily of PKC (cPKC) signaling to affect cytotoxicity and mutagenicity in CL3 human non-small-cell lung adenocarcinoma cells. Pb specifically promoted membrane localization of the α isoform of PKC in CL3 cells. Pb also elicited Raf-1 activation as measured by the induction of phospho-Raf-1S338 and the dissociation from the Raf-1 kinase inhibitor protein. Inhibition of cPKC activity using Gö6976 or depletion of PKCα by introducing specific small interfering RNA blocked the induction of phospho-Raf-1S338, phospho-MKK1/2 and phospho-ERK1/2 in cells exposed to Pb. Intriguingly, declining PKCα enhanced the Pb cytotoxicity and revealed the Pb mutagenicity at the hprt gene. The results suggest that PKCα is obligatory for activation of the Raf-1–MKK1/2–ERK1/2 signaling module and plays a defensive role against cytotoxicity and mutagenicity following Pb exposure. Results obtained in this study also support our previous report showing that ERK1/2 activity is involved in preventing Pb genotoxicity.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 250, Issue 1, 19 August 2008, Pages 55–61
نویسندگان
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