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Mediators of Inflammation
Volume 2015, Article ID 536238, 12 pages
Research Article

S-Nitrosoglutathione Reductase Plays Opposite Roles in SH-SY5Y Models of Parkinson’s Disease and Amyotrophic Lateral Sclerosis

1Cell Stress and Survival Unit, Danish Cancer Society Research Center, 2100 Copenhagen, Denmark
2IRCCS Santa Lucia Foundation and Department of Biology, University of Rome “Tor Vergata”, 00133 Rome, Italy
3The Beatson Institute for Cancer Research, Cancer Research UK, Glasgow G61 1BD, UK
4Unit of Radiation Biology and Human Health, ENEA-Casaccia, 00123 Rome, Italy
5Institute for Translational Pharmacology, CNR, 00133 Rome, Italy

Received 26 December 2014; Revised 22 March 2015; Accepted 13 May 2015

Academic Editor: Jan G. C. van Amsterdam

Copyright © 2015 Salvatore Rizza et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Oxidative and nitrosative stresses have been reported as detrimental phenomena concurring to the onset of several neurodegenerative diseases. Here we reported that the ectopic modulation of the denitrosylating enzyme S-nitrosoglutathione reductase (GSNOR) differently impinges on the phenotype of two SH-SY5Y-based in vitro models of neurodegeneration, namely, Parkinson’s disease (PD) and familial amyotrophic lateral sclerosis (fALS). In particular, we provide evidence that GSNOR-knocking down protects SH-SY5Y against PD toxins, while, by contrast, its upregulation is required for G93A-SOD1 expressing cells resistance to NO-releasing drugs. Although completely opposite, both conditions are characterized by Nrf2 localization in the nuclear compartment: in the first case induced by GSNOR silencing, while in the second one underlying the antinitrosative response. Overall, our results demonstrate that GSNOR expression has different effect on neuronal viability in dependence on the stimulus applied and suggest that GSNOR could be a responsive gene downstream of Nrf2 activation.