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

Sara Baratchi, Rupinder K Kanwar, Jagat R Kanwar

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22 Citations (Scopus)

Abstract

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.
Original languageEnglish
Article numbere15865
Number of pages8
JournalPLoS ONE
Volume6
Issue number1
DOIs
Publication statusPublished - 2011
Externally publishedYes

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