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Effects of peroxynitrite-induced protein tyrosine nitration on insulin-stimulated tyrosine phosphorylation in HepG2 cells

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Abstract

Tyrosine nitration by peroxynitrite can affect signal transduction pathways involving tyrosine phosphorylation. The present study was undertaken to investigate the effects of peroxynitrite-induced protein tyrosine nitration on insulin-stimulated tyrosine phosphorylation in HepG2 cells. We show here that exposure of HepG2 cells to peroxynitrite led to a dose-dependent increase in tyrosine nitration of cellular proteins, mainly membrane and nuclear proteins. Furthermore, peroxynitrite induced differential responses in tyrosine phosphorylation of membrane proteins as well as cytosolic proteins according to peroxynitrite concentrations used. Our findings indicate at low concentrations peroxynitrite upregulates the insulin signaling and may operate as a signaling molecule, but at higher concentrations peroxynitrite downregulates the insulin signaling and may be involved in insulin resistance, suggesting peroxynitrite plays a dual role in regulation of the insulin signaling.

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Abbreviations

BSA:

Bovine serum albumin

Da:

Dalton

DMEM:

Dulbecco’s modified Eagle’s medium

DTT:

Dithiothreitol

ECL:

Enhanced chemiluminescence

IR:

Insulin receptor

IRS:

Insulin receptor substrate

NCS:

Newborn calf serum

NT:

Nitrotyrosine

PAGE:

Polyacrylamide gel electrophoresis

PBS:

Phosphate buffered saline

PI3 K:

Phosphatidylinositol 3 kinase

PKB:

Protein kinase B

PTP-ases:

Phosphotyrosine phosphatases

ROS:

Reactive oxygen species

SIN-1:

3-Morpholinosydnonimine hydrochloride

T-TBS:

Tris-buffered saline with Tween

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 20671037), the Science Foundation of Huazhong University of Science and Technology (No. 0101013180), and Graduates’ Innovation Fund of Huazhong University of Science and Technology (No. HF04052006170).

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  1. Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, People’s Republic of China

    Jun Zhou, Haidong Li, Jinhong Zeng & Kaixun Huang

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  1. Jun Zhou
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  2. Haidong Li
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  3. Jinhong Zeng
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  4. Kaixun Huang
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Correspondence to Kaixun Huang.

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Zhou, J., Li, H., Zeng, J. et al. Effects of peroxynitrite-induced protein tyrosine nitration on insulin-stimulated tyrosine phosphorylation in HepG2 cells. Mol Cell Biochem 331, 49–57 (2009). https://doi.org/10.1007/s11010-009-0144-z

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