title: Exercise-induced immunosuppression: roles of reactive oxygen species and 5'-AMP-activated protein kinase dephosphorylation within immune cells.
abstract: 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% VO2max) 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 microM) 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.
authors.affiliation: Cardiff School of Health Sciences, University of Wales Institute, Cardiff CF5 2YB, UK.
authors.forename: Hannah
authors.initials: H
authors.lastname: Moir
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hughes
authors.forename: Stephen
authors.initials: S
authors.lastname: Potter
authors.forename: Craig
authors.initials: C
authors.lastname: Sims
authors.forename: Lee R
authors.initials: LR
authors.lastname: Butcher
authors.forename: Nia A
authors.initials: NA
authors.lastname: Davies
authors.forename: Kenneth
authors.initials: K
authors.lastname: Verheggen
authors.forename: Kenneth P
authors.initials: KP
authors.lastname: Jones
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Thomas
authors.forename: Richard
authors.initials: R
authors.lastname: Webb
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D001642:Bicycling; D020013:Calcium Signaling; D002478:Cells, Cultured; D019040:E-Selectin / Q000097:blood; D015444:Exercise; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007070:Immunoglobulin A / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012420:Running; D012463:Saliva / Q000276:immunology; D013997:Time Factors; D055815:Young Adult
chemical_list: D000975:Antioxidants; D019040:E-Selectin; D007070:Immunoglobulin A; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human; D001205:Ascorbic Acid