کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8290167 | 1536344 | 2014 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Insulin-like modulation of Akt/FoxO signaling by copper ions is independent of insulin receptor
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Copper ions are known to induce insulin-like effects in various cell lines, stimulating the phosphoinositide 3â²-kinase (PI3K)/Akt signaling cascade and leading to the phosphorylation of downstream targets, including FoxO transcription factors. The aim of this work was to study the role of insulin- and IGF1-receptors (IR and IGF1R) in insulin-like signaling induced by copper in HepG2 human hepatoma cells. Cells were exposed to Cu(II) at various concentrations for up to 60Â min. While Akt and FoxO1a/FoxO3a were strongly phosphorylated in copper- and insulin-treated cells at all time points studied, only faint tyrosine phosphorylation of IR/IGF1R was detected in cells exposed to Cu(II) by either immunoprecipitation/immunoblot or by immunoblotting using phospho-specific antibodies, whereas insulin triggered strong phosphorylation at these sites. Pharmacological inhibition of IR/IGF1R modestly attenuated Cu-induced Akt and FoxO phosphorylation, whereas no attenuation of Cu-induced Akt activation was achieved by siRNA-mediated IR depletion. Cu(II)-induced FoxO1a nuclear exclusion was only slightly impaired by pharmacological inhibition of IR/IGF1R, whereas insulin-induced effects were blunted. In contrast, genistein, a broad-spectrum tyrosine kinase inhibitor, at concentrations not affecting IR/IGF1R, attenuated Cu(II)-induced Akt phosphorylation, pointing to the requirement of tyrosine kinases other than IR/IGF1R for Cu(II)-induced signaling.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Archives of Biochemistry and Biophysics - Volume 558, 15 September 2014, Pages 42-50
Journal: Archives of Biochemistry and Biophysics - Volume 558, 15 September 2014, Pages 42-50
نویسندگان
Ingrit Hamann, Kerstin Petroll, Larson Grimm, Andrea Hartwig, Lars-Oliver Klotz,