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

(2010) JOURNAL OF APPLIED PHYSIOLOGY. 108(5). p.1284-1292
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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.
Keywords
HYDROGEN-PEROXIDE, ENDOTHELIAL-CELLS, SKELETAL-MUSCLE, NADPH OXIDASE, STIMULATION, ACTIVATION, AMPK, INTERLEUKIN-6, INFLAMMATION, MONOCYTES, 5 '-adenosine monophosphate-activated protein kinase, mononuclear cells

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MLA
Moir, Hannah et al. “Exercise-induced Immunosuppression: Roles of Reactive Oxygen Species and 5  ’-AMP-activated Protein Kinase Dephosphorylation Within Immune Cells.” JOURNAL OF APPLIED PHYSIOLOGY 108.5 (2010): 1284–1292. Print.
APA
Moir, H., Hughes, M. G., Potter, S., Sims, C., Butcher, L. R., Davies, N. A., Verheggen, K., et al. (2010). Exercise-induced immunosuppression: roles of reactive oxygen species and 5  ’-AMP-activated protein kinase dephosphorylation within immune cells. JOURNAL OF APPLIED PHYSIOLOGY, 108(5), 1284–1292.
Chicago author-date
Moir, Hannah, Michael G Hughes, Stephen Potter, Craig Sims, Lee R Butcher, Nia Anne Davies, Kenneth Verheggen, Kenneth Philip Jones, Andrew W Thomas, and Richard Webb. 2010. “Exercise-induced Immunosuppression: Roles of Reactive Oxygen Species and 5  ’-AMP-activated Protein Kinase Dephosphorylation Within Immune Cells.” Journal of Applied Physiology 108 (5): 1284–1292.
Chicago author-date (all authors)
Moir, Hannah, Michael G Hughes, Stephen Potter, Craig Sims, Lee R Butcher, Nia Anne Davies, Kenneth Verheggen, Kenneth Philip Jones, Andrew W Thomas, and Richard Webb. 2010. “Exercise-induced Immunosuppression: Roles of Reactive Oxygen Species and 5  ’-AMP-activated Protein Kinase Dephosphorylation Within Immune Cells.” Journal of Applied Physiology 108 (5): 1284–1292.
Vancouver
1.
Moir H, Hughes MG, Potter S, Sims C, Butcher LR, Davies NA, et al. Exercise-induced immunosuppression: roles of reactive oxygen species and 5  ’-AMP-activated protein kinase dephosphorylation within immune cells. JOURNAL OF APPLIED PHYSIOLOGY. 2010;108(5):1284–92.
IEEE
[1]
H. Moir et al., “Exercise-induced immunosuppression: roles of reactive oxygen species and 5 ’-AMP-activated protein kinase dephosphorylation within immune cells,” JOURNAL OF APPLIED PHYSIOLOGY, vol. 108, no. 5, pp. 1284–1292, 2010.
@article{875812,
  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.},
  author       = {Moir, Hannah and Hughes, Michael G and Potter, Stephen and Sims, Craig and Butcher, Lee R and Davies, Nia Anne and Verheggen, Kenneth and Jones, Kenneth Philip and Thomas, Andrew W and Webb, Richard},
  issn         = {8750-7587},
  journal      = {JOURNAL OF APPLIED PHYSIOLOGY},
  keywords     = {HYDROGEN-PEROXIDE,ENDOTHELIAL-CELLS,SKELETAL-MUSCLE,NADPH OXIDASE,STIMULATION,ACTIVATION,AMPK,INTERLEUKIN-6,INFLAMMATION,MONOCYTES,5 '-adenosine monophosphate-activated protein kinase,mononuclear cells},
  language     = {eng},
  number       = {5},
  pages        = {1284--1292},
  title        = {Exercise-induced immunosuppression: roles of reactive oxygen species and 5 '-AMP-activated protein kinase dephosphorylation within immune cells},
  url          = {http://dx.doi.org/10.1152/japplphysiol.00737.2009},
  volume       = {108},
  year         = {2010},
}

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