Journal
JOURNAL OF MOLECULAR NEUROSCIENCE
Volume 61, Issue 1, Pages 123-131Publisher
HUMANA PRESS INC
DOI: 10.1007/s12031-016-0807-7
Keywords
Oxidative stress; Reactive oxygen species; Protease inhibitor; Neuroprotection; Hippocampal neurons
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Funding
- Intramural Research Program of the Eunice Kennedy Shriver National Institute of Health and Human Development, National Institutes of Health, USA
- Auckland Medical Research Foundation
- University of Auckland
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Oxidative stress plays a critical role in neuronal injury and is associated with various neurological diseases. Here, we explored the potential protective effect of neuroserpin against oxidative stress in primary cultured hippocampal neurons. Our results show that neuroserpin inhibits H2O2-induced neurotoxicity in hippocampal cultures as measured by WST, LDH release, and TUNEL assays. We found that neuroserpin enhanced the activation of AKT in cultures subjected to oxidative stress and that the AKT inhibitor Ly294002 blocked this neuroprotective effect. Neuroserpin increased the expression of the anti-apoptotic protein BCL-2 and blocked the activation of caspase-3. Neuroserpin did not increase the level of neuroprotection over levels seen in neurons transduced with a BCL-2 expression vector, and an inhibitor of Trk receptors, K252a, did not block neuroserpin's effect. Taken together, our study demonstrates that neuroserpin protects against oxidative stress-induced dysfunction and death of primary cultured hippocampal neurons through the AKT-BCL-2 signaling pathway through a mechanism that does not involve the Trk receptors and leads to inhibition of caspase-3 activation.
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