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Neurochemical Research

, Volume 36, Issue 1, pp 67–75 | Cite as

Sonic Hedgehog Protects Cortical Neurons Against Oxidative Stress

  • Ruo-Lian Dai
  • Sheng-Yin Zhu
  • Yuan-Peng Xia
  • Ling Mao
  • Yuan-Wu Mei
  • Yu-Fang Yao
  • Yu-Mei Xue
  • Bo Hu
ORIGINAL PAPER

Abstract

Oxidative stress is one of the most important pathological mechanisms in neurodegenerative diseases and ischemia. Recent studies have indicated that the sonic hedgehog (SHH) signaling pathway is involved in these diseases, but the underlying mechanisms remains elusive. Here we report that the SHH pathway was activated in primary cultured cortical neurons after exposure to hydrogen peroxide (H2O2). H2O2 treatment decreased the cell viability of neurons, and inhibition of endogenous SHH signaling exacerbated its neurotoxicity. Activation of SHH signaling protected neurons from H2O2-induced apoptosis and increased the cell viability while those effects were partially reversed by blocking SHH signals. Exogenous SHH increased the activities of Superoxide dismutase (SOD) and Glutathione peroxidase (GSH-PX) in H2O2-treated neurons and decreased production of Malondialdehyde (MDA). It also promoted expression of the anti-apoptotic gene Bcl-2 and inhibited expression of pro-apoptotic gene Bax. Activation of SHH signals upregulated both Neurotrophic factors vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF). Pretreatment with SHH inhibited the activation of ERK (extracellular signal-regulated kinases) signals induced by H2O2. Our findings demonstrate that activation of SHH signaling protects cortical neurons against oxidative stress and suggest a potential role of SHH for the clinic treatments of brain ischemia and neurodegenerative disorders.

Keywords

Sonic hedgehog signaling Oxidative stress Hydrogen peroxide Apoptosis 

Notes

Acknowledgment

This work was supported by grants from the Program of National Natural Science Foundation of China (No. 30600189).

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Ruo-Lian Dai
    • 1
  • Sheng-Yin Zhu
    • 1
  • Yuan-Peng Xia
    • 1
  • Ling Mao
    • 1
  • Yuan-Wu Mei
    • 1
  • Yu-Fang Yao
    • 1
  • Yu-Mei Xue
    • 1
  • Bo Hu
    • 1
  1. 1.Department of Neurology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

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