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

By Hannah Moir, Michael G Hughes, Stephen Potter, Craig Sims, Lee R Butcher, Nia Anne Davies, Kenneth Verheggen, Kenneth Philip Jones, Andrew W Thomas and Richard Webb

Abstract

We have previously proposed 5'AMP-Activated Protein Kinase (AMPK) dephosphorylation within immune cells as an intracellular mechanism linking exercise and immunosuppression. Here, AMPK phosphorylation underwent transient (<1h) decreases (53.8±7.2% basal) immediately after exercise (45 min of cycling at 70% VO2 max) 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 signalling mechanisms distinct from changes in cellular AMP:ATP ratios, reactive oxygen species (ROS) and intracellular Ca2+ signalling ([Ca2+]i) 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; 4h; 50μM) 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 exercise's AMPK-dephosphorylating effect. In contrast, exercise-induced Ca2+ signalling 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 thence immune function - in the context of exercise-induced immunosuppression

Topics: Biology and Life Sciences, HYDROGEN-PEROXIDE, ENDOTHELIAL-CELLS, SKELETAL-MUSCLE, NADPH OXIDASE, STIMULATION, ACTIVATION, AMPK, INTERLEUKIN-6, INFLAMMATION, MONOCYTES, 5 '-adenosine monophosphate-activated protein kinase, mononuclear cells
Publisher: 'American Physiological Society'
Year: 2010
DOI identifier: 10.1152/japplphysiol.00737.2009
OAI identifier: oai:archive.ugent.be:875812
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