NOX2 inhibition impairs early muscle gene expression induced by a single exercise bout

Carlos Henríquez-Olguín, Alexis Díaz-Vegas, Yildy Utreras-Mendoza, Cristian Campos, Manuel Arias-Calderón, Paola Llanos, Ariel Contreras-Ferrat, Alejandra Espinosa, Francisco Altamirano, Enrique Jaimovich, Denisse M. Valladares

Resultado de la investigación: Article

23 Citas (Scopus)

Resumen

Reactive oxygen species (ROS) participate as signaling molecules in response to exercise in skeletal muscle. However, the source of ROS and the molecular mechanisms involved in these phenomena are still not completely understood. The aim of this work was to study the role of skeletal muscle NADPH oxidase isoform 2 (NOX2) in the molecular response to physical exercise in skeletal muscle. BALB/c mice, pre-treated with a NOX2 inhibitor, apocynin, (3 mg/kg) or vehicle for 3 days, were swim-exercised for 60 min. Phospho-p47phox levels were significantly upregulated by exercise in flexor digitorum brevis (FDB). Moreover, exercise significantly increased NOX2 complex assembly (p47phox-gp91phox interaction) demonstrated by both proximity ligation assay and co-immunoprecipitation. Exercise-induced NOX2 activation was completely inhibited by apocynin treatment. As expected, exercise increased the mRNA levels of manganese superoxide dismutase (MnSOD), glutathione peroxidase (GPx), citrate synthase (CS), mitochondrial transcription factor A (tfam) and interleukin-6 (IL-I6) in FDB muscles. Moreover, the apocynin treatment was associated to a reduced activation of p38 MAP kinase, ERK 1/2, and NF-κB signaling pathways after a single bout of exercise. Additionally, the increase in plasma IL-6 elicited by exercise was decreased in apocynin-treated mice compared with the exercised vehicle-group (p < 0.001). These results were corroborated using gp91-dstat in an in vitro exercise model. In conclusion, NOX2 inhibition by both apocynin and gp91dstat, alters the intracellular signaling to exercise and electrical stimuli in skeletal muscle, suggesting that NOX2 plays a critical role in molecular response to an acute exercise.

Idioma originalEnglish
Número de artículo282
PublicaciónFrontiers in Physiology
Volumen7
N.ºJUL
DOI
EstadoPublished - 14 jul 2016

Huella dactilar

NADPH Oxidase
Protein Isoforms
Gene Expression
Muscles
Skeletal Muscle
Interleukin-6
Reactive Oxygen Species
Exercise
Citrate (si)-Synthase
p38 Mitogen-Activated Protein Kinases
Glutathione Peroxidase
Immunoprecipitation
Superoxide Dismutase
Ligation
acetovanillone
Messenger RNA

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Citar esto

Henríquez-Olguín, C., Díaz-Vegas, A., Utreras-Mendoza, Y., Campos, C., Arias-Calderón, M., Llanos, P., ... Valladares, D. M. (2016). NOX2 inhibition impairs early muscle gene expression induced by a single exercise bout. Frontiers in Physiology, 7(JUL), [282]. https://doi.org/10.3389/fphys.2016.00282
Henríquez-Olguín, Carlos ; Díaz-Vegas, Alexis ; Utreras-Mendoza, Yildy ; Campos, Cristian ; Arias-Calderón, Manuel ; Llanos, Paola ; Contreras-Ferrat, Ariel ; Espinosa, Alejandra ; Altamirano, Francisco ; Jaimovich, Enrique ; Valladares, Denisse M. / NOX2 inhibition impairs early muscle gene expression induced by a single exercise bout. En: Frontiers in Physiology. 2016 ; Vol. 7, N.º JUL.
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abstract = "Reactive oxygen species (ROS) participate as signaling molecules in response to exercise in skeletal muscle. However, the source of ROS and the molecular mechanisms involved in these phenomena are still not completely understood. The aim of this work was to study the role of skeletal muscle NADPH oxidase isoform 2 (NOX2) in the molecular response to physical exercise in skeletal muscle. BALB/c mice, pre-treated with a NOX2 inhibitor, apocynin, (3 mg/kg) or vehicle for 3 days, were swim-exercised for 60 min. Phospho-p47phox levels were significantly upregulated by exercise in flexor digitorum brevis (FDB). Moreover, exercise significantly increased NOX2 complex assembly (p47phox-gp91phox interaction) demonstrated by both proximity ligation assay and co-immunoprecipitation. Exercise-induced NOX2 activation was completely inhibited by apocynin treatment. As expected, exercise increased the mRNA levels of manganese superoxide dismutase (MnSOD), glutathione peroxidase (GPx), citrate synthase (CS), mitochondrial transcription factor A (tfam) and interleukin-6 (IL-I6) in FDB muscles. Moreover, the apocynin treatment was associated to a reduced activation of p38 MAP kinase, ERK 1/2, and NF-κB signaling pathways after a single bout of exercise. Additionally, the increase in plasma IL-6 elicited by exercise was decreased in apocynin-treated mice compared with the exercised vehicle-group (p < 0.001). These results were corroborated using gp91-dstat in an in vitro exercise model. In conclusion, NOX2 inhibition by both apocynin and gp91dstat, alters the intracellular signaling to exercise and electrical stimuli in skeletal muscle, suggesting that NOX2 plays a critical role in molecular response to an acute exercise.",
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Henríquez-Olguín, C, Díaz-Vegas, A, Utreras-Mendoza, Y, Campos, C, Arias-Calderón, M, Llanos, P, Contreras-Ferrat, A, Espinosa, A, Altamirano, F, Jaimovich, E & Valladares, DM 2016, 'NOX2 inhibition impairs early muscle gene expression induced by a single exercise bout', Frontiers in Physiology, vol. 7, n.º JUL, 282. https://doi.org/10.3389/fphys.2016.00282

NOX2 inhibition impairs early muscle gene expression induced by a single exercise bout. / Henríquez-Olguín, Carlos; Díaz-Vegas, Alexis; Utreras-Mendoza, Yildy; Campos, Cristian; Arias-Calderón, Manuel; Llanos, Paola; Contreras-Ferrat, Ariel; Espinosa, Alejandra; Altamirano, Francisco; Jaimovich, Enrique; Valladares, Denisse M.

En: Frontiers in Physiology, Vol. 7, N.º JUL, 282, 14.07.2016.

Resultado de la investigación: Article

TY - JOUR

T1 - NOX2 inhibition impairs early muscle gene expression induced by a single exercise bout

AU - Henríquez-Olguín, Carlos

AU - Díaz-Vegas, Alexis

AU - Utreras-Mendoza, Yildy

AU - Campos, Cristian

AU - Arias-Calderón, Manuel

AU - Llanos, Paola

AU - Contreras-Ferrat, Ariel

AU - Espinosa, Alejandra

AU - Altamirano, Francisco

AU - Jaimovich, Enrique

AU - Valladares, Denisse M.

PY - 2016/7/14

Y1 - 2016/7/14

N2 - Reactive oxygen species (ROS) participate as signaling molecules in response to exercise in skeletal muscle. However, the source of ROS and the molecular mechanisms involved in these phenomena are still not completely understood. The aim of this work was to study the role of skeletal muscle NADPH oxidase isoform 2 (NOX2) in the molecular response to physical exercise in skeletal muscle. BALB/c mice, pre-treated with a NOX2 inhibitor, apocynin, (3 mg/kg) or vehicle for 3 days, were swim-exercised for 60 min. Phospho-p47phox levels were significantly upregulated by exercise in flexor digitorum brevis (FDB). Moreover, exercise significantly increased NOX2 complex assembly (p47phox-gp91phox interaction) demonstrated by both proximity ligation assay and co-immunoprecipitation. Exercise-induced NOX2 activation was completely inhibited by apocynin treatment. As expected, exercise increased the mRNA levels of manganese superoxide dismutase (MnSOD), glutathione peroxidase (GPx), citrate synthase (CS), mitochondrial transcription factor A (tfam) and interleukin-6 (IL-I6) in FDB muscles. Moreover, the apocynin treatment was associated to a reduced activation of p38 MAP kinase, ERK 1/2, and NF-κB signaling pathways after a single bout of exercise. Additionally, the increase in plasma IL-6 elicited by exercise was decreased in apocynin-treated mice compared with the exercised vehicle-group (p < 0.001). These results were corroborated using gp91-dstat in an in vitro exercise model. In conclusion, NOX2 inhibition by both apocynin and gp91dstat, alters the intracellular signaling to exercise and electrical stimuli in skeletal muscle, suggesting that NOX2 plays a critical role in molecular response to an acute exercise.

AB - Reactive oxygen species (ROS) participate as signaling molecules in response to exercise in skeletal muscle. However, the source of ROS and the molecular mechanisms involved in these phenomena are still not completely understood. The aim of this work was to study the role of skeletal muscle NADPH oxidase isoform 2 (NOX2) in the molecular response to physical exercise in skeletal muscle. BALB/c mice, pre-treated with a NOX2 inhibitor, apocynin, (3 mg/kg) or vehicle for 3 days, were swim-exercised for 60 min. Phospho-p47phox levels were significantly upregulated by exercise in flexor digitorum brevis (FDB). Moreover, exercise significantly increased NOX2 complex assembly (p47phox-gp91phox interaction) demonstrated by both proximity ligation assay and co-immunoprecipitation. Exercise-induced NOX2 activation was completely inhibited by apocynin treatment. As expected, exercise increased the mRNA levels of manganese superoxide dismutase (MnSOD), glutathione peroxidase (GPx), citrate synthase (CS), mitochondrial transcription factor A (tfam) and interleukin-6 (IL-I6) in FDB muscles. Moreover, the apocynin treatment was associated to a reduced activation of p38 MAP kinase, ERK 1/2, and NF-κB signaling pathways after a single bout of exercise. Additionally, the increase in plasma IL-6 elicited by exercise was decreased in apocynin-treated mice compared with the exercised vehicle-group (p < 0.001). These results were corroborated using gp91-dstat in an in vitro exercise model. In conclusion, NOX2 inhibition by both apocynin and gp91dstat, alters the intracellular signaling to exercise and electrical stimuli in skeletal muscle, suggesting that NOX2 plays a critical role in molecular response to an acute exercise.

KW - Antioxidant defense

KW - IL-6

KW - Muscle adaptation

KW - NADPH oxidase

KW - Reactive oxygen species

KW - Redox signaling

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U2 - 10.3389/fphys.2016.00282

DO - 10.3389/fphys.2016.00282

M3 - Article

AN - SCOPUS:84981484980

VL - 7

JO - Frontiers in Physiology

JF - Frontiers in Physiology

SN - 1664-042X

IS - JUL

M1 - 282

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Henríquez-Olguín C, Díaz-Vegas A, Utreras-Mendoza Y, Campos C, Arias-Calderón M, Llanos P y otros. NOX2 inhibition impairs early muscle gene expression induced by a single exercise bout. Frontiers in Physiology. 2016 jul 14;7(JUL). 282. https://doi.org/10.3389/fphys.2016.00282