Exercise-induced immunosuppression: roles of reactive oxygen species and 5′-AMP-activated protein kinase dephosphorylation within immune cells

We previously proposed 5′-AMP-activated protein kinase (AMPK) dephosphorylation within immune cells as an intracellular mechanism linking exercise and immunosuppression. In this study, AMPK phosphorylation underwent transient (<1 h) decreases (53.8 ± 7.2% basal) immediately after exercise (45 min...

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Main Authors: Moir, H., Hughes, M., Potter, S., Sims, Craig, Butcher, L., Davies, N., Verheggen, K., Jones, K., Thomas, A., Webb, R.
Format: Journal Article
Language:English
Published: American Physiological Society 2010
Subjects:
Online Access:http://hdl.handle.net/20.500.11937/76560
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author Moir, H.
Hughes, M.
Potter, S.
Sims, Craig
Butcher, L.
Davies, N.
Verheggen, K.
Jones, K.
Thomas, A.
Webb, R.
author_facet Moir, H.
Hughes, M.
Potter, S.
Sims, Craig
Butcher, L.
Davies, N.
Verheggen, K.
Jones, K.
Thomas, A.
Webb, R.
author_sort Moir, H.
building Curtin Institutional Repository
collection Online Access
description We previously proposed 5′-AMP-activated protein kinase (AMPK) dephosphorylation within immune cells as an intracellular mechanism linking exercise and immunosuppression. In this study, AMPK phosphorylation underwent transient (<1 h) decreases (53.8 ± 7.2% basal) immediately after exercise (45 min of cycling at 70% V̇o2max) in a cohort of 16 adult male participants. Similar effects were seen with running. However, because exercise-induced inactivation of AMPK was previously shown to occur in an AMP-independent manner, the means by which AMPK is inactivated in this context is not yet clear. To investigate the hypothesis that exercise-induced inactivation of AMPK is mediated via signaling mechanisms distinct from changes in cellular AMP-to-ATP ratios, reactive oxygen species (ROS) and intracellular Ca2+ signaling were investigated in mononuclear cells before and after exercise and in cultured monocytic MM6 cells. In in vitro studies, treatment with an antioxidant (ascorbic acid, 4 h, 50 μM) decreased MM6 cell intracellular ROS levels (88.0 ± 5.2% basal) and induced dephosphorylation of AMPK (44.7 ± 17.6% basal). By analogy, the fact that exercise decreased mononuclear cell ROS content (32.8 ± 16.6% basal), possibly due to downregulation (43.4 ± 8.0% basal) of mRNA for NOX2, the catalytic subunit of the cytoplasmic ROS-generating enzyme NADPH oxidase, may provide an explanation for the AMPK-dephosphorylating effect of exercise. In contrast, exercise-induced Ca2+ signaling events did not seem to be coupled to changes in AMPK activity. Thus we propose that the exercise-induced decreases in both intracellular ROS and AMPK phosphorylation seen in this study constitute evidence supporting a role for ROS in controlling AMPK, and hence immune function, in the context of exercise-induced immunosuppression.
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spelling curtin-20.500.11937-765602019-10-18T03:49:05Z Exercise-induced immunosuppression: roles of reactive oxygen species and 5′-AMP-activated protein kinase dephosphorylation within immune cells Moir, H. Hughes, M. Potter, S. Sims, Craig Butcher, L. Davies, N. Verheggen, K. Jones, K. Thomas, A. Webb, R. 1101 - Medical Biochemistry and Metabolomics We previously proposed 5′-AMP-activated protein kinase (AMPK) dephosphorylation within immune cells as an intracellular mechanism linking exercise and immunosuppression. In this study, AMPK phosphorylation underwent transient (<1 h) decreases (53.8 ± 7.2% basal) immediately after exercise (45 min of cycling at 70% V̇o2max) in a cohort of 16 adult male participants. Similar effects were seen with running. However, because exercise-induced inactivation of AMPK was previously shown to occur in an AMP-independent manner, the means by which AMPK is inactivated in this context is not yet clear. To investigate the hypothesis that exercise-induced inactivation of AMPK is mediated via signaling mechanisms distinct from changes in cellular AMP-to-ATP ratios, reactive oxygen species (ROS) and intracellular Ca2+ signaling were investigated in mononuclear cells before and after exercise and in cultured monocytic MM6 cells. In in vitro studies, treatment with an antioxidant (ascorbic acid, 4 h, 50 μM) decreased MM6 cell intracellular ROS levels (88.0 ± 5.2% basal) and induced dephosphorylation of AMPK (44.7 ± 17.6% basal). By analogy, the fact that exercise decreased mononuclear cell ROS content (32.8 ± 16.6% basal), possibly due to downregulation (43.4 ± 8.0% basal) of mRNA for NOX2, the catalytic subunit of the cytoplasmic ROS-generating enzyme NADPH oxidase, may provide an explanation for the AMPK-dephosphorylating effect of exercise. In contrast, exercise-induced Ca2+ signaling events did not seem to be coupled to changes in AMPK activity. Thus we propose that the exercise-induced decreases in both intracellular ROS and AMPK phosphorylation seen in this study constitute evidence supporting a role for ROS in controlling AMPK, and hence immune function, in the context of exercise-induced immunosuppression. 2010 Journal Article http://hdl.handle.net/20.500.11937/76560 10.1152/japplphysiol.00737.2009 English American Physiological Society restricted
spellingShingle 1101 - Medical Biochemistry and Metabolomics
Moir, H.
Hughes, M.
Potter, S.
Sims, Craig
Butcher, L.
Davies, N.
Verheggen, K.
Jones, K.
Thomas, A.
Webb, R.
Exercise-induced immunosuppression: roles of reactive oxygen species and 5′-AMP-activated protein kinase dephosphorylation within immune cells
title Exercise-induced immunosuppression: roles of reactive oxygen species and 5′-AMP-activated protein kinase dephosphorylation within immune cells
title_full Exercise-induced immunosuppression: roles of reactive oxygen species and 5′-AMP-activated protein kinase dephosphorylation within immune cells
title_fullStr Exercise-induced immunosuppression: roles of reactive oxygen species and 5′-AMP-activated protein kinase dephosphorylation within immune cells
title_full_unstemmed Exercise-induced immunosuppression: roles of reactive oxygen species and 5′-AMP-activated protein kinase dephosphorylation within immune cells
title_short Exercise-induced immunosuppression: roles of reactive oxygen species and 5′-AMP-activated protein kinase dephosphorylation within immune cells
title_sort exercise-induced immunosuppression: roles of reactive oxygen species and 5′-amp-activated protein kinase dephosphorylation within immune cells
topic 1101 - Medical Biochemistry and Metabolomics
url http://hdl.handle.net/20.500.11937/76560