Chronic Intermittent Hypoxia-Induced Diaphragm Muscle Weakness Is NADPH Oxidase-2 Dependent
Chronic intermittent hypoxia (CIH)-induced redox alterations underlie diaphragm muscle dysfunction. We sought to establish if NADPH oxidase 2 (NOX2)-derived reactive oxygen species (ROS) underpin CIH-induced changes in diaphragm muscle, which manifest as impaired muscle performance. Adult male mice...
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MDPI AG
2023-07-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/14/1834 |
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| author | Sarah E. Drummond David P. Burns Sarah El Maghrani Oscar Ziegler Vincent Healy Ken D. O’Halloran |
| author_facet | Sarah E. Drummond David P. Burns Sarah El Maghrani Oscar Ziegler Vincent Healy Ken D. O’Halloran |
| author_sort | Sarah E. Drummond |
| collection | DOAJ |
| description | Chronic intermittent hypoxia (CIH)-induced redox alterations underlie diaphragm muscle dysfunction. We sought to establish if NADPH oxidase 2 (NOX2)-derived reactive oxygen species (ROS) underpin CIH-induced changes in diaphragm muscle, which manifest as impaired muscle performance. Adult male mice (C57BL/6J) were assigned to one of three groups: normoxic controls (sham); chronic intermittent hypoxia-exposed (CIH, 12 cycles/hour, 8 h/day for 14 days); and CIH + apocynin (NOX2 inhibitor, 2 mM) administered in the drinking water throughout exposure to CIH. In separate studies, we examined sham and CIH-exposed NOX2-null mice (B6.129S-<i>Cybb<sup>TM1Din</sup></i><sup>/J</sup>). Apocynin co-treatment or NOX2 deletion proved efficacious in entirely preventing diaphragm muscle dysfunction following exposure to CIH. Exposure to CIH had no effect on NOX2 expression. However, NOX4 mRNA expression was increased following exposure to CIH in wild-type and NOX2 null mice. There was no evidence of overt CIH-induced oxidative stress. A NOX2-dependent increase in genes related to muscle regeneration, antioxidant capacity, and autophagy and atrophy was evident following exposure to CIH. We suggest that NOX-dependent CIH-induced diaphragm muscle weakness has the potential to affect ventilatory and non-ventilatory performance of the respiratory system. Therapeutic strategies employing NOX2 blockade may function as an adjunct therapy to improve diaphragm muscle performance and reduce disease burden in diseases characterised by exposure to CIH, such as obstructive sleep apnoea. |
| first_indexed | 2024-03-11T01:12:21Z |
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| id | doaj.art-20458eec60c5449b8a186724f256ab7b |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T01:12:21Z |
| publishDate | 2023-07-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-20458eec60c5449b8a186724f256ab7b2023-11-18T18:45:49ZengMDPI AGCells2073-44092023-07-011214183410.3390/cells12141834Chronic Intermittent Hypoxia-Induced Diaphragm Muscle Weakness Is NADPH Oxidase-2 DependentSarah E. Drummond0David P. Burns1Sarah El Maghrani2Oscar Ziegler3Vincent Healy4Ken D. O’Halloran5Department of Physiology, School of Medicine, College of Medicine and Health, University College Cork, T12 XF62 Cork, IrelandDepartment of Physiology, School of Medicine, College of Medicine and Health, University College Cork, T12 XF62 Cork, IrelandDepartment of Physiology, School of Medicine, College of Medicine and Health, University College Cork, T12 XF62 Cork, IrelandDepartment of Physiology, School of Medicine, College of Medicine and Health, University College Cork, T12 XF62 Cork, IrelandDepartment of Physiology, School of Medicine, College of Medicine and Health, University College Cork, T12 XF62 Cork, IrelandDepartment of Physiology, School of Medicine, College of Medicine and Health, University College Cork, T12 XF62 Cork, IrelandChronic intermittent hypoxia (CIH)-induced redox alterations underlie diaphragm muscle dysfunction. We sought to establish if NADPH oxidase 2 (NOX2)-derived reactive oxygen species (ROS) underpin CIH-induced changes in diaphragm muscle, which manifest as impaired muscle performance. Adult male mice (C57BL/6J) were assigned to one of three groups: normoxic controls (sham); chronic intermittent hypoxia-exposed (CIH, 12 cycles/hour, 8 h/day for 14 days); and CIH + apocynin (NOX2 inhibitor, 2 mM) administered in the drinking water throughout exposure to CIH. In separate studies, we examined sham and CIH-exposed NOX2-null mice (B6.129S-<i>Cybb<sup>TM1Din</sup></i><sup>/J</sup>). Apocynin co-treatment or NOX2 deletion proved efficacious in entirely preventing diaphragm muscle dysfunction following exposure to CIH. Exposure to CIH had no effect on NOX2 expression. However, NOX4 mRNA expression was increased following exposure to CIH in wild-type and NOX2 null mice. There was no evidence of overt CIH-induced oxidative stress. A NOX2-dependent increase in genes related to muscle regeneration, antioxidant capacity, and autophagy and atrophy was evident following exposure to CIH. We suggest that NOX-dependent CIH-induced diaphragm muscle weakness has the potential to affect ventilatory and non-ventilatory performance of the respiratory system. Therapeutic strategies employing NOX2 blockade may function as an adjunct therapy to improve diaphragm muscle performance and reduce disease burden in diseases characterised by exposure to CIH, such as obstructive sleep apnoea.https://www.mdpi.com/2073-4409/12/14/1834obstructive sleep apnoeadiaphragmchronic intermittent hypoxiaNADPH oxidase |
| spellingShingle | Sarah E. Drummond David P. Burns Sarah El Maghrani Oscar Ziegler Vincent Healy Ken D. O’Halloran Chronic Intermittent Hypoxia-Induced Diaphragm Muscle Weakness Is NADPH Oxidase-2 Dependent Cells obstructive sleep apnoea diaphragm chronic intermittent hypoxia NADPH oxidase |
| title | Chronic Intermittent Hypoxia-Induced Diaphragm Muscle Weakness Is NADPH Oxidase-2 Dependent |
| title_full | Chronic Intermittent Hypoxia-Induced Diaphragm Muscle Weakness Is NADPH Oxidase-2 Dependent |
| title_fullStr | Chronic Intermittent Hypoxia-Induced Diaphragm Muscle Weakness Is NADPH Oxidase-2 Dependent |
| title_full_unstemmed | Chronic Intermittent Hypoxia-Induced Diaphragm Muscle Weakness Is NADPH Oxidase-2 Dependent |
| title_short | Chronic Intermittent Hypoxia-Induced Diaphragm Muscle Weakness Is NADPH Oxidase-2 Dependent |
| title_sort | chronic intermittent hypoxia induced diaphragm muscle weakness is nadph oxidase 2 dependent |
| topic | obstructive sleep apnoea diaphragm chronic intermittent hypoxia NADPH oxidase |
| url | https://www.mdpi.com/2073-4409/12/14/1834 |
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