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

Autor: Jonathan Teoh, Joanne Chieng, Sherif Boulos, Bruno P. Meloni, Neville W. Knuckey
Rok vydání: 2014
Předmět:
Zdroj: Cellular and Molecular Neurobiology. 34:379-392
ISSN: 1573-6830
0272-4340
DOI: 10.1007/s10571-013-0023-8
Popis: 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.
Databáze: OpenAIRE
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