S-Nitrosoglutathione Reductase Plays Opposite Roles in SH-SY5Y Models of Parkinson's Disease and Amyotrophic Lateral Sclerosis.
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.
Cell Stress and Survival Unit, Danish Cancer Society Research Center, 2100 Copenhagen, Denmark.
Salvatore
S
Rizza
IRCCS Santa Lucia Foundation and Department of Biology, University of Rome "Tor Vergata", 00133 Rome, Italy.
Claudia
C
Cirotti
Cell Stress and Survival Unit, Danish Cancer Society Research Center, 2100 Copenhagen, Denmark ; IRCCS Santa Lucia Foundation and Department of Biology, University of Rome "Tor Vergata", 00133 Rome, Italy.
Costanza
C
Montagna
IRCCS Santa Lucia Foundation and Department of Biology, University of Rome "Tor Vergata", 00133 Rome, Italy ; The Beatson Institute for Cancer Research, Cancer Research UK, Glasgow G61 1BD, UK.
Simone
S
Cardaci
Unit of Radiation Biology and Human Health, ENEA-Casaccia, 00123 Rome, Italy.
Claudia
C
Consales
IRCCS Santa Lucia Foundation and Department of Biology, University of Rome "Tor Vergata", 00133 Rome, Italy ; Institute for Translational Pharmacology, CNR, 00133 Rome, Italy.
Mauro
M
Cozzolino
IRCCS Santa Lucia Foundation and Department of Biology, University of Rome "Tor Vergata", 00133 Rome, Italy.
Maria Teresa
MT
Carrì
Cell Stress and Survival Unit, Danish Cancer Society Research Center, 2100 Copenhagen, Denmark ; IRCCS Santa Lucia Foundation and Department of Biology, University of Rome "Tor Vergata", 00133 Rome, Italy.
Francesco
F
Cecconi
Cell Stress and Survival Unit, Danish Cancer Society Research Center, 2100 Copenhagen, Denmark ; IRCCS Santa Lucia Foundation and Department of Biology, University of Rome "Tor Vergata", 00133 Rome, Italy.
Giuseppe
G
Filomeni
D000445:Aldehyde Oxidoreductases / Q000378:metabolism*; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D005260:Female; D020868:Gene Silencing; D006801:Humans; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000473:pathology; D009474:Neurons / Q000473:pathology; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000378:metabolism*; D010641:Phenotype; D034741:RNA, Small Interfering / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism
D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D034741:RNA, Small Interfering; D000445:Aldehyde Oxidoreductases; C087006:formaldehyde dehydrogenase, glutathione-independent