TY - JOUR

T1 - The emerging roles of nicotinamide adenine dinucleotide phosphate oxidase 2 in skeletal muscle redox signaling and metabolism

AU - Henríquez-Olguín, Carlos

AU - Boronat, Susanna

AU - Cabello-Verrugio, Claudio

AU - Jaimovich, Enrique

AU - Hidalgo, Elena

AU - Jensen, Thomas Elbenhardt

N1 - CURIS 2019 NEXS 347

PY - 2019

Y1 - 2019

N2 - Significance: Skeletal muscle is a crucial tissue to whole-body locomotion and metabolic health. Reactive oxygen species (ROS) have emerged as intracellular messengers participating in both physiological and pathological adaptations in skeletal muscle. A complex interplay between ROS-producing enzymes and antioxidant networks exists in different subcellular compartments of mature skeletal muscle. Recent evidence suggests that NADPH oxidases (NOX) are a major source of contraction- and insulin-stimulated oxidants production, but may paradoxically also contribute to muscle insulin resistance and atrophy.Recent advances: Pharmacological and molecular biological tools, including redox-sensitive probes and transgenic mouse models, have generated novel insights into compartmentalized redox signaling and suggested that NOX2 contributes to redox control of skeletal muscle metabolism. Critical issues: Major outstanding questions in skeletal muscle include where NOX2 activation occurs under different conditions in health and disease, how NOX2 activation is regulated, how superoxide/ H2O2 generated by NOX2 reaches the cytosol, what the signaling mediators are downstream of NOX2, and the role of NOX2 for different physiological and pathophysiological processes. Future directions: Future research should utilize and expand the current redox-signaling toolbox to clarify the NOX2-dependent mechanisms in skeletal muscle and determine whether the proposed functions of NOX2 in cells and animal models are conserved into man.

AB - Significance: Skeletal muscle is a crucial tissue to whole-body locomotion and metabolic health. Reactive oxygen species (ROS) have emerged as intracellular messengers participating in both physiological and pathological adaptations in skeletal muscle. A complex interplay between ROS-producing enzymes and antioxidant networks exists in different subcellular compartments of mature skeletal muscle. Recent evidence suggests that NADPH oxidases (NOX) are a major source of contraction- and insulin-stimulated oxidants production, but may paradoxically also contribute to muscle insulin resistance and atrophy.Recent advances: Pharmacological and molecular biological tools, including redox-sensitive probes and transgenic mouse models, have generated novel insights into compartmentalized redox signaling and suggested that NOX2 contributes to redox control of skeletal muscle metabolism. Critical issues: Major outstanding questions in skeletal muscle include where NOX2 activation occurs under different conditions in health and disease, how NOX2 activation is regulated, how superoxide/ H2O2 generated by NOX2 reaches the cytosol, what the signaling mediators are downstream of NOX2, and the role of NOX2 for different physiological and pathophysiological processes. Future directions: Future research should utilize and expand the current redox-signaling toolbox to clarify the NOX2-dependent mechanisms in skeletal muscle and determine whether the proposed functions of NOX2 in cells and animal models are conserved into man.

KW - Faculty of Science

KW - Exercise

KW - Skeletal muscle

KW - Glucose metabolism

KW - Insulin resistance

KW - Atrophy

U2 - 10.1089/ars.2018.7678

DO - 10.1089/ars.2018.7678

M3 - Review

C2 - 31588777

VL - 31

SP - 1371

EP - 1410

JO - Antioxidants and Redox Signaling

JF - Antioxidants and Redox Signaling

SN - 1523-0864

IS - 8

ER -