Novel survivin mutant protects differentiated SK-N-SH human neuroblastoma cells from activated T-cell neurotoxicity

Sara Baratchi, Rupinder K Kanwar, Jagat R Kanwar

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13 Citations (Scopus)

Abstract

Currently, there are no known treatments for protection of axonal loss associated with neuroinflammatory diseases such as multiple sclerosis (MS). Survivin is a member of the inhibitors of the apoptosis (IAP) family of proteins that its neuroprotective effects have not been studied. We demonstrate here that SurR9-C84A, a survivin mutant, exhibits a neuroprotective role against the cytotoxic effects of activated T-cell infiltrates, such as granzyme B (GrB). The activated T-cell supernatants induce toxicity on differentiated SK-N-SH cells, which is associated with the loss of Ca2+ homeostasis, the increased population of dead cells, mitochondrial membrane depolarisation, and the accelerated expression of cyclinD1, caspase3 and Fas, as observed for most apoptotic cells. Alternatively, the pre-treatment with SurR9-C84A reduces the population of dead cells by balancing the cytosolic Ca2+ homeostasis, decreasing the level of mitochondrial depolarisation, and also reducing the expression of cyclinD1 and caspase3. Our findings suggest that SurR9-C84A has a neuroprotective effect against the cytotoxins existing in activated T-cell supernatants including GrB.
Original languageEnglish
Pages (from-to)18 - 28
Number of pages11
JournalJournal of Neuroimmunology
Volume233
Issue number1-2
DOIs
Publication statusPublished - 2011
Externally publishedYes

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