Nuclear Phospho-SOD1 Protects DNA from Oxidative Stress Damage in Amyotrophic Lateral Sclerosis
Articolo
Data di Pubblicazione:
2019
Citazione:
Nuclear Phospho-SOD1 Protects DNA from Oxidative Stress Damage in Amyotrophic Lateral Sclerosis / M. Bordoni, O. Pansarasa, M. Dell’Orco, V. Crippa, S. Gagliardi, D. Sproviero, S. Bernuzzi, L. Diamanti, M. Ceroni, G. Tedeschi, A. Poletti, C. Cereda. - In: JOURNAL OF CLINICAL MEDICINE. - ISSN 2077-0383. - 8:5(2019 May 22).
Abstract:
We already demonstrated that in peripheral blood mononuclear cells (PBMCs) of sporadic amyotrophic lateral sclerosis (sALS) patients, superoxide dismutase 1 (SOD1) was present in an aggregated form in the cytoplasmic compartment. Here, we investigated the possible effect of soluble SOD1 decrease and its consequent aggregation. We found an increase in DNA damage in patients PBMCs characterized by a high level of aggregated SOD1, while we found no DNA damage in PBMCs with normal soluble SOD1. We found an activation of ataxia-telangiectasia-mutated (ATM)/Chk2 and ATM and Rad3-related (ATR)/Chk1 DNA damage response pathways, which lead to phosphorylation of SOD1. Moreover, data showed that phosphorylation allows SOD1 to shift from the cytoplasm to the nucleus, protecting DNA from oxidative damage. Such pathway was finally confirmed in our cellular model. Our data lead us to suppose that in a sub-group of patients this physiologic pathway is non-functional, leading to an accumulation of DNA damage that causes the death of particularly susceptible cells, like motor neurons. In conclusion, during oxidative stress SOD1 is phosphorylated by Chk2 leading to its translocation in the nuclear compartment, in which SOD1 protects DNA from oxidative damage
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
oxidative stress; ALS; SOD1; DNA damage; peripheral blood mononuclear cells
Elenco autori:
M. Bordoni, O. Pansarasa, M. Dell’Orco, V. Crippa, S. Gagliardi, D. Sproviero, S. Bernuzzi, L. Diamanti, M. Ceroni, G. Tedeschi, A. Poletti, C. Cereda
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