These authors contributed equally to this work.
Protective action of erythropoietin on neuronal damage induced by activated microglia
Article first published online: 1 MAR 2013
© 2013 The Authors Journal compilation © 2013 FEBS
Volume 280, Issue 7, pages 1630–1642, April 2013
How to Cite
Wenker, S. D., Chamorro, M. E., Vittori, D. C. and Nesse, A. B. (2013), Protective action of erythropoietin on neuronal damage induced by activated microglia. FEBS Journal, 280: 1630–1642. doi: 10.1111/febs.12172
- Issue published online: 27 MAR 2013
- Article first published online: 1 MAR 2013
- Accepted manuscript online: 6 FEB 2013 04:14AM EST
- Manuscript Accepted: 22 JAN 2013
- Manuscript Revised: 22 DEC 2012
- Manuscript Received: 7 NOV 2012
- University of Buenos Aires and the National Council of Scientific and Technical Research
Inflammation is a physiological defense response, but may also represent a potential pathological process in neurological diseases. In this regard, microglia have a crucial role in either progression or amelioration of degenerative neuronal damage. Because of the role of hypoxia in pro-inflammatory mechanisms in the nervous system, and the potential anti-inflammatory protective effect of erythropoietin (Epo), we focused our investigation on the role of this factor on activation of microglia and neuroprotection. Activation of microglial cells (EOC-2) was achieved by chemical hypoxia induced by cobalt chloride (CoCl2) and characterized by increased levels of nitrite, tumor necrosis factor-α and reactive oxygen species production, as well as up-regulation of inducible nitric oxide synthase expression. Under these conditions, cell proliferation data and proliferating cell nuclear antigen (PCNA) staining demonstrated a mitogenic effect of chemical hypoxia. Even though pre-treatment with Epo did not prevent nitrite production, inducible nitric oxide synthase protein expression or tumor necrosis factor-α secretion, it prevented the oxidative stress induced by CoCl2 as well as cell proliferation. Neuronal cells (SH-SY5Y) cultured in the presence of conditioned medium from activated EOC-2 cells or macrophages (RAW 264.7) developed significant apoptosis, an effect that was abolished by Epo via Epo/Epo receptor activation. The results show that even though Epo did not exert a direct anti-inflammatory effect on microglia activation, it did increase the resistance of neurons to subsequent damage from pro-inflammatory agents. In addition to its anti-apoptotic ability, the Epo antioxidant effect may have an indirect influence on neuronal survival by modulation of the pro-inflammatory environment.