RGD Reference Report - Sonic hedgehog protects cortical neurons against oxidative stress. - Rat Genome Database

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Sonic hedgehog protects cortical neurons against oxidative stress.

Authors: Dai, Ruo-Lian  Zhu, Sheng-Yin  Xia, Yuan-Peng  Mao, Ling  Mei, Yuan-Wu  Yao, Yu-Fang  Xue, Yu-Mei  Hu, Bo 
Citation: Dai RL, etal., Neurochem Res. 2011 Jan;36(1):67-75. doi: 10.1007/s11064-010-0264-6. Epub 2010 Sep 17.
RGD ID: 12879463
Pubmed: PMID:20848190   (View Abstract at PubMed)
DOI: DOI:10.1007/s11064-010-0264-6   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of neuron apoptotic process  IMP 12879463 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Smo  (smoothened, frizzled class receptor)


Additional Information