Erythropoietin increases neuronal NDPKA expression, and NDPKA up-regulation as well as exogenous application protects cortical neurons from in vitro ischemia-related insults.

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.

• Authors: Jonathan Teoh, Sherif Boulos, Joanne Chieng, Neville W Knuckey, Bruno P Meloni
• Journal: Cellular and molecular neurobiology (Cell Mol Neurobiol) Vol. 34 Issue 3 Pg. 379-92 (Apr 2014) ISSN: 1573-6830 [Electronic] United States
• PMID: 24395206 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Neuroprotective Agents
• Erythropoietin
• Nucleoside-Diphosphate Kinase
• nucleoside diphosphate kinase, rat

Topics

• Animals
• Brain Ischemia (metabolism, prevention & control)
• Cell Survival (drug effects, physiology)
• Cells, Cultured
• Cerebral Cortex (drug effects, metabolism)
• Erythropoietin (pharmacology, therapeutic use)
• Gene Expression Regulation
• HEK293 Cells
• Humans
• Neurons (drug effects, metabolism)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Nucleoside-Diphosphate Kinase (biosynthesis, pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Up-Regulation (drug effects, physiology)