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Neuroserpin Attenuates H2O2-Induced Oxidative Stress in Hippocampal Neurons via AKT and BCL-2 Signaling Pathways

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Abstract

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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Acknowledgments

This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Health and Human Development, National Institutes of Health, USA, and grants from the Auckland Medical Research Foundation and the University of Auckland to NPB.

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Authors and Affiliations

  1. Section on Cellular Neurobiology, Program on Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892, USA

    Yong Cheng & Y. Peng Loh

  2. School of Biological Sciences, Centre for Brain Research and Brain Research New Zealand, Rangahau Roro Aotearoa, University of Auckland, 3a Symonds Street 92019, Auckland, 1142, New Zealand

    Nigel P. Birch

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  1. Yong Cheng
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  2. Y. Peng Loh
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Correspondence to Nigel P. Birch.

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All animal procedures were approved by the Animal Care and Use Committee, NICHD, NIH.

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Cheng, Y., Loh, Y.P. & Birch, N.P. Neuroserpin Attenuates H2O2-Induced Oxidative Stress in Hippocampal Neurons via AKT and BCL-2 Signaling Pathways. J Mol Neurosci 61, 123–131 (2017). https://doi.org/10.1007/s12031-016-0807-7

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  • DOI: https://doi.org/10.1007/s12031-016-0807-7

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