title: PO2 cycling reduces diaphragm fatigue by attenuating ROS formation.
abstract: Prolonged muscle exposure to low PO2 conditions may cause oxidative stress resulting in severe muscular injuries. We hypothesize that PO2 cycling preconditioning, which involves brief cycles of diaphragmatic muscle exposure to a low oxygen level (40 Torr) followed by a high oxygen level (550 Torr), can reduce intracellular reactive oxygen species (ROS) as well as attenuate muscle fatigue in mouse diaphragm under low PO2. Accordingly, dihydrofluorescein (a fluorescent probe) was used to monitor muscular ROS production in real time with confocal microscopy during a lower PO2 condition. In the control group with no PO2 cycling, intracellular ROS formation did not appear during the first 15 min of the low PO2 period. However, after 20 min of low PO2, ROS levels increased significantly by ∼30% compared to baseline, and this increase continued until the end of the 30 min low PO2 condition. Conversely, muscles treated with PO2 cycling showed a complete absence of enhanced fluorescence emission throughout the entire low PO2 period. Furthermore, PO2 cycling-treated diaphragm exhibited increased fatigue resistance during prolonged low PO2 period compared to control. Thus, our data suggest that PO2 cycling mitigates diaphragm fatigue during prolonged low PO2. Although the exact mechanism for this protection remains to be elucidated, it is likely that through limiting excessive ROS levels, PO2 cycling initiates ROS-related antioxidant defenses.
authors.affiliation: Radiologic Sciences and Respiratory Therapy Division, School of Health and Rehabilitation Sciences, Davis Heart and Lung Research Institute, The Ohio State University College of Medicine, Columbus, Ohio, United States of America; Department of Biological Sciences, Oakland University, Rochester, Michigan, United States of America.
authors.forename: Li
authors.initials: L
authors.lastname: Zuo
authors.affiliation: Division of Pulmonary, Allergy, Critical Care & Sleep Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States of America.
authors.forename: Philip T
authors.initials: PT
authors.lastname: Diaz
authors.affiliation: Department of Biology, Kalamazoo College, Kalamazoo, Michigan, United States of America.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Chien
authors.affiliation: Radiologic Sciences and Respiratory Therapy Division, School of Health and Rehabilitation Sciences, Davis Heart and Lung Research Institute, The Ohio State University College of Medicine, Columbus, Ohio, United States of America; Department of Biological Sciences, Oakland University, Rochester, Michigan, United States of America.
authors.forename: William J
authors.initials: WJ
authors.lastname: Roberts
authors.affiliation: Department of Biological Sciences, Oakland University, Rochester, Michigan, United States of America.
authors.forename: Juliana
authors.initials: J
authors.lastname: Kishek
authors.affiliation: Division of Sports Medicine, Department of Family Medicine, Sports Health and Performance Institute, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Best
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Wagner
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D003964:Diaphragm / Q000378:metabolism / Q000473:pathology; D005221:Fatigue / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D018613:Microscopy, Confocal; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology / Q000648:ultrastructure; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen / Q000097:blood*; D010313:Partial Pressure; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D010100:Oxygen