During the last decade, it has been shown that the activation of NRF2 and the binding to electrophile-responsive element (EpREs), stimulates the expression of a great number of genes responsible for the synthesis of phase I and phase II proteins, including antioxidants enzymes and heme oxygenase-1 (HO-1). This critical cell response occurs in cardiovascular, degenerative and chronic infective diseases aggravated by a chronic oxidative stress. In our previous reports we have shown that ozonated plasma is able to up-regulate HO-1 expression in endothelial cells. In the present work we investigated a candidate mechanism involved in this process. After treatment with increasing doses of ozonated serum (20, 40 and 80 μg/mL O3 per mL of serum), a clear dose dependent activation of NRF2 and the subsequent induction of HO-1 and NAD(P)H quinone oxidoreductase 1( NQO1) was observed. This effect was also present when cells were treated with serum and hydrogen peroxide (H2O2) or serum and 4-hydroxynonenal (4HNE). Moreover, the treatment with ozonated serum was associated with a dose-dependent activation of extracellular-signal-regulated kinases (ERK1/2) and p38 MAP kinases (p38), not directly involved in NRF2 activation. These data, provide a new insight on the mechanism responsible for the induction of HO-1 expression by ozonated serum in the endothelium, and have a practical importance as an expedient approach to the treatment of patients with both effective orthodox drugs and ozonated autohemotherapy, targeted to the restoration of redox homeostasis.
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|Titolo:||NRF2 activation is involved in ozonated human serum upregulation of HO-1 in endothelial cells|
|Citazione:||NRF2 activation is involved in ozonated human serum upregulation of HO-1 in endothelial cells / Pecorelli, Alessandra; Bocci, V.; Acquaviva, Alessandra; Belmonte, Giuseppe; Gardi, Concetta; Virgili, F.; Ciccoli, L.; Valacchi, G.. - In: TOXICOLOGY AND APPLIED PHARMACOLOGY. - ISSN 0041-008X. - 267:1(2013), pp. 30-40.|
|Appare nelle tipologie:||1.1 Articolo in rivista|