Survivin mutant protects differentiated dopaminergic SK-N-SH cells against oxidative stress

• Published in: PloS one 2011-01, Vol.6 (1), p.e15865
• Main Authors: Baratchi, Sara, Kanwar, Rupinder K, Kanwar, Jagat R
• Format: Article
• Language: English
• Subjects: Acids; Alzheimer's disease; Amyotrophic lateral sclerosis; Antioxidants; Apoptosis; Ataxia; Biology; Biomedical research; Biotechnology; Brain research; Cancer; Catalase; Cell cycle; Cell death; Cell Death - drug effects; Cell Death - genetics; Cell Line, Tumor; Chromosomes; Cyclin D1; Depolarization; Development and progression; Dopamine; Dopamine - metabolism; Dopamine receptors; Encephalitis; Homeostasis; Humans; Hydrogen Peroxide; Hypoxia; IAP protein; Immunology; Inhibitor of Apoptosis Proteins - pharmacokinetics; Ischemia; Laboratories; Medicine; Mitochondria; Movement disorders; Mutant Proteins - pharmacology; Nervous system; Nervous system diseases; Neurodegenerative diseases; Neurological diseases; Neurons; Neuroprotection; Neuroprotective Agents - pharmacology; Neurosciences; Neurosurgery; Neurotoxicity; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - genetics; Parkinson's disease; Pathogenesis; Peptides; Peroxidase; Proteins; Rodents; Survivin; Toxicity; Trends
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0015865

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.