The adaptor protein SH2B1β reduces hydrogen peroxide-induced cell death in PC12 cells and hippocampal neurons

Wan-Chen Lu,Hui-Chien Hsu,Chien-Jen Chen,Hsin-Ling Hsu,Linyi Chen

doi:10.1186/1750-2187-5-17

Abstract

BackgroundSH2B1β is a signaling adaptor protein that has been shown to promote neuronal differentiation in PC12 cells and is necessary for the survival of sympathetic neurons. However, the mechanism by which SH2B1β may influence cell survival is not known.ResultsIn this study, we investigated the role of SH2B1β in oxidative stress-induced cell death. Our results suggest that overexpressing SH2B1β reduced H2O2-induced, caspase 3-dependent apoptosis in PC12 cells and hippocampal neurons. In response to H2O2, overexpressing SH2B1β enhanced PI3K (phosphatidylinositol 3-kinas)-AKT (protein kinase B) and MEK (MAPK/ERK kinase)-extracellular-signal regulated kinases 1 and 2 (ERK1/2) signaling pathways. We further demonstrated that SH2B1β was able to reduce H2O2-induced nuclear localization of FoxO1 and 3a transcription factors, which lie downstream of PI3K-AKT and MEK-ERK1/2 pathways. Moreover, overexpressing SH2B1β reduced the expression of Fas ligand (FasL), one of the target genes of FoxOs.ConclusionsOverexpressing the adaptor protein SH2B1β enhanced H2O2-induced PI3K-AKT and MEK-ERK1/2 signaling, reduced nucleus-localized FoxOs and the expression of a pro-apoptotic gene, FasL.

Highlights

Oxidative stress resulting from overload of toxic reactive oxygen species (ROS) is common in the etiology of human diseases
We investigated the role of SH2B1β in oxidative stress-induced cell death, signaling, FoxOs distribution and their target gene expression
Overexpressing SH2B1β reduces hydrogen peroxideinduced cell death in PC12 cells To determine whether SH2B1β affects oxidative stressinduced cell death, PC12 cells stably expressing GFP (PC12-GFP cell line) or GFP-SH2B1β (PC12-SH2B1β cell line) were treated without (Figure 1A, B) or with (Figure 1C, D, E, F) H2O2

Summary

Introduction

Oxidative stress resulting from overload of toxic reactive oxygen species (ROS) is common in the etiology of human diseases. It has been implicated in various neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease [1,2,3,4]. A number of signaling pathways are evolved to protect cells from ROS-induced damages, including phosphatidylinositol 3-kinase (PI3K)-AKT pathway, mitogen-. SH2B1β is a signaling adaptor protein that has been shown to promote neuronal differentiation in PC12 cells and is necessary for the survival of sympathetic neurons. The mechanism by which SH2B1β may influence cell survival is not known

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Results

Conclusion