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Hydrogen peroxide-dependent oxidative stress induces SOD1 transcription gene is independent from Nrf2 transcription factor in a cellular model of neurodegeneration.

Autori

Dell'Orco M, Milani P, Arrigoni L, Pansarasa O, Sardone V, Maffioli E, Polveraccio F, Bordoni M, Diamanti L, Peverali FA, Tedeschi G, Cereda C.

Riferimenti

BIOCHIMICA ET BIOPHYSICA ACTA (BBA) - GENE REGULATORY MECHANISMS 1859(2) 315-323, 2016

Autori CNR

PEVERALI

Moduli

Abstract

BACKGROUND: It is still unclear whether oxidative stress (OS) is a disease consequence or is directly involved in the etiology of neurodegenerative disorders (NDs) onset and/or progression; however, many of these conditions are associated with increased levels of oxidation markers and damaged cell components. Previously we demonstrated the accumulation of reactive oxygen species (ROS) and increased SOD1 gene expression within H2O2 SH-SY5Y treated cells recapitulating pathological features of Amyotrophic Lateral Sclerosis (ALS). Since we observed a post-transcriptional regulation of SOD1 gene in this cellular model of ALS, we investigated the transcriptional regulation of SOD1 mRNA under oxidative stress (OS). RESULTS: In response to H2O2 treatment, PolII increased its association to SOD1 promoter. Electrophoretic mobility shift assays (EMSA) and mass spectrometry analyses on SOD1 promoter highlighted the formation of a transcriptional complex bound to the ARE sequences. WB analyses showed that in our in vitro model, H2O2 exposure increases Nrf2 nuclear fraction while IP experiments confirmed its phosphorylation and release from Keap1 inhibition. However, H2O2 treatment did not modify Nrf2 binding on SOD1 promoter, which seems to be regulated by different TFs. CONCLUSIONS: Although our data suggest that SOD1 is transcriptionally regulated in response to OS, Nrf2 does not appear to associate with SOD1 promoter in this model of ALS. Our results open new perspectives in the comprehension of two key antioxidant pathways involved in neurodegeneration. Copyright 2015. Published by Elsevier B.V.

Link all articolo

http://www.sciencedirect.com/science/article/pii/S1874939915002485

Parole Chiave

Note

10.1016/j.bbagrm.2015.11.009

Indietro


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