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Erythropoietin Increases Neuronal NDPKA Expression, and NDPKA Up-Regulation as well as Exogenous Application Protects Cortical Neurons from In Vitro Ischemia-Related Insults

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Abstract

Using proteomics, we identified nucleoside diphosphate kinase A (NDPKA; also known as NME/NM23 nucleoside diphosphate kinase 1: NME1) to be up-regulated in primary cortical neuronal cultures by erythropoietin (EPO) preconditioning. To investigate a neuroprotective role of NDPKA in neurons, we used a RNAi construct to knock-down and an adenoviral vector to overexpress the protein in cortical neuronal cultures prior to exposure to three ischemia-related injury models; excitotoxicity (l-glutamic acid), oxidative stress (hydrogen peroxide), and in vitro ischemia (oxygen-glucose deprivation). NDPKA down-regulation had no effect on neuronal viability following injury. By contrast, NDPKA up-regulation increased neuronal survival in all three-injury models. Similarly, treatment with NDPKA recombinant protein increased neuronal survival, but only against in vitro ischemia and excitotoxicity. These findings indicate that the NDPKA protein may confer a neuroprotective advantage following injury. Furthermore, as exogenous NDPKA protein was neuroprotective, it suggests that a cell surface receptor may be activated by NDPKA leading to a protective cell-signaling response. Taken together both NDPKAs intracellular and extracellular neuroprotective actions suggest that the protein is a legitimate therapeutic target for the design of drugs to limit neuronal death following stroke and other forms of brain injury.

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Acknowledgments

This study was supported by the Neuromuscular Foundation of Western Australia, the Sir Charles Gairdner Hospital Research Fund, and by a University of Western Australia postgraduate research scholarship to Jonathan Teoh.

Conflict of interest

The authors have no competing financial interests.

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Authors and Affiliations

  1. Centre for Neuromuscular and Neurological Disorders, The University of Western Australia, Nedlands, WA, 6009, Australia

    Jonathan Teoh, Sherif Boulos, Joanne Chieng, Neville W. Knuckey & Bruno P. Meloni

  2. Western Australian Neuroscience Research Institute, A Block, 4th Floor, QEII Medical Centre, Verdun St, Nedlands, WA, 6009, Australia

    Jonathan Teoh, Sherif Boulos, Joanne Chieng, Neville W. Knuckey & Bruno P. Meloni

  3. Department of Neurosurgery, Sir Charles Gairdner Hospital, Nedlands, WA, Australia

    Neville W. Knuckey & Bruno P. Meloni

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  1. Jonathan Teoh
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  2. Sherif Boulos
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  4. Neville W. Knuckey
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  5. Bruno P. Meloni
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Correspondence to Bruno P. Meloni.

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Teoh, J., Boulos, S., Chieng, J. et al. Erythropoietin Increases Neuronal NDPKA Expression, and NDPKA Up-Regulation as well as Exogenous Application Protects Cortical Neurons from In Vitro Ischemia-Related Insults. Cell Mol Neurobiol 34, 379–392 (2014). https://doi.org/10.1007/s10571-013-0023-8

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