Survivin mutant protects differentiated dopaminergic SK-N-SH cells against oxidative stress.
Oxidative stress is due to an imbalance of antioxidant/pro-oxidant homeostasis and is associated with the progression of several neurological diseases, including Parkinson's and Alzheimer's disease and amyotrophic lateral sclerosis. Furthermore, oxidative stress is responsible for the neuronal loss and dysfunction associated with disease pathogenesis. Survivin is a member of the inhibitors of the apoptosis (IAP) family of proteins, but its neuroprotective effects have not been studied. Here, we demonstrate that SurR9-C84A, a survivin mutant, has neuroprotective effects against H₂O₂-induced neurotoxicity. Our results show that H₂O₂ toxicity is associated with an increase in cell death, mitochondrial membrane depolarisation, and the expression of cyclin D1 and caspases 9 and 3. In addition, pre-treatment with SurR9-C84A reduces cell death by decreasing both the level of mitochondrial depolarisation and the expression of cyclin D1 and caspases 9 and 3. We further show that SurR9-C84A increases the antioxidant activity of GSH-peroxidase and catalase, and effectively counteracts oxidant activity following exposure to H₂O₂. These results suggest for the first time that SurR9-C84A is a promising treatment to protect neuronal cells against H₂O₂-induced neurotoxicity.
Laboratory of Immunology and Molecular Biomedical Research, Centre for Biotechnology and Interdisciplinary Biosciences, Institute for Technology Research and Innovation, Deakin University, Waurn Ponds, Victoria, Australia.
Sara
S
Baratchi
Rupinder K
RK
Kanwar
Jagat R
JR
Kanwar
D000975:Antioxidants; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide; D051034:Inhibitor of Apoptosis Proteins / Q000493:pharmacokinetics*; D050505:Mutant Proteins / Q000494:pharmacology*; D009474:Neurons; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D000077022:Survivin
D000975:Antioxidants; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D050505:Mutant Proteins; D018696:Neuroprotective Agents; D000077022:Survivin; D006861:Hydrogen Peroxide; D004298:Dopamine
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