Oxidative stress is involved in the pathogenesis of Duchenne muscular dystrophy (DMD), an X-linked genetic disorder caused by mutations in the dystrophin gene and characterized by progressive, lethal muscle degeneration and chronic inflammation. In this study, we explored the expression and signaling pathway of a master player of the anti-oxidant and anti-inflammatory response, namely NRF2, in muscle biopsies of DMD patients. We classified DMD patients in two age groups (Class I, 0-2 years and Class II, 2-9 years), in order to evaluate the antioxidant pathway expression during the disease progression. We observed that altered enzymatic antioxidant responses, increased levels of oxidized glutathione and oxidative damage are differently modulated in the two age classes of patients and well correlate with the severity of pathology. Interestingly, we also observed a modulation of relevant markers of the inflammatory response, such as heme oxygenase 1 and IL-6, suggesting a link between oxidative stress and chronic inflammatory response. Of note, using a transgenic mouse model, we demonstrated that IL-6 overexpression parallels the antioxidant expression profile and the severity of dystrophic muscle observed in DMD patients. This study advances our understanding of the pathogenic mechanisms underlying DMD and defines the critical role of oxidative stress on muscle wasting with clear implications for disease pathogenesis and therapy in human.

Oxidative stress in Duchenne muscular dystrophy: focus on the NRF2 redox pathway / Petrillo, Sara; Pelosi, Laura; Piemonte, Fiorella; Travaglini, Lorena; Forcina, Laura; Catteruccia, Michela; Petrini, Stefania; Verardo, Margherita; D'Amico, Adele; Musaro', Antonio; Bertini, Enrico. - In: HUMAN MOLECULAR GENETICS. - ISSN 0964-6906. - STAMPA. - 26:14(2017), pp. 2781-2790. [10.1093/hmg/ddx173]

Oxidative stress in Duchenne muscular dystrophy: focus on the NRF2 redox pathway

PELOSI, LAURA;FORCINA, LAURA;MUSARO', Antonio;
2017

Abstract

Oxidative stress is involved in the pathogenesis of Duchenne muscular dystrophy (DMD), an X-linked genetic disorder caused by mutations in the dystrophin gene and characterized by progressive, lethal muscle degeneration and chronic inflammation. In this study, we explored the expression and signaling pathway of a master player of the anti-oxidant and anti-inflammatory response, namely NRF2, in muscle biopsies of DMD patients. We classified DMD patients in two age groups (Class I, 0-2 years and Class II, 2-9 years), in order to evaluate the antioxidant pathway expression during the disease progression. We observed that altered enzymatic antioxidant responses, increased levels of oxidized glutathione and oxidative damage are differently modulated in the two age classes of patients and well correlate with the severity of pathology. Interestingly, we also observed a modulation of relevant markers of the inflammatory response, such as heme oxygenase 1 and IL-6, suggesting a link between oxidative stress and chronic inflammatory response. Of note, using a transgenic mouse model, we demonstrated that IL-6 overexpression parallels the antioxidant expression profile and the severity of dystrophic muscle observed in DMD patients. This study advances our understanding of the pathogenic mechanisms underlying DMD and defines the critical role of oxidative stress on muscle wasting with clear implications for disease pathogenesis and therapy in human.
2017
antioxidants; oxidative stress; duchenne's muscular dystrophy; biopsy; glutathione disulfide; oxidation-reduction; interleukin-6; pathology; chronic inflammation
01 Pubblicazione su rivista::01a Articolo in rivista
Oxidative stress in Duchenne muscular dystrophy: focus on the NRF2 redox pathway / Petrillo, Sara; Pelosi, Laura; Piemonte, Fiorella; Travaglini, Lorena; Forcina, Laura; Catteruccia, Michela; Petrini, Stefania; Verardo, Margherita; D'Amico, Adele; Musaro', Antonio; Bertini, Enrico. - In: HUMAN MOLECULAR GENETICS. - ISSN 0964-6906. - STAMPA. - 26:14(2017), pp. 2781-2790. [10.1093/hmg/ddx173]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/972252
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