AMPK inactivation in mononuclear cells: a potential intracellular mechanism for exercise-induced immunosuppression

Moir, Hannah; Butcher, Lee; Jones, Ken; Hughes, Michael G.; Neale, Huw NealeH.; Jia, Huidong JiaH.; Al-Ismaily, Zuleikha Al-IsmailyZ.; Webb, Richard

doi:10.1139/h07-135

Cited by 12 publications

(21 citation statements)

References 27 publications

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“…Changes in AMPK activity can be transient as reported previously in IEC-6 cells and in primary cultures of rat hepatocytes exposed to adenosine [50] or in alveolar epithelial cells exposed to elevated CO 2 [51] or in prostate cancer cells exposed to adiponectin [52]. AMPK is also transiently inactivated by exercise in mononuclear cells [53]. Taken together, our results show that SSW increases lipid accumulation in hepatocytes by increasing SREBP-1 activity via the inactivation of AMPK.…”

Section: Discussionmentioning

confidence: 76%

Second-hand smoke stimulates lipid accumulation in the liver by modulating AMPK and SREBP-1

Shyy

Martins‐Green

2009

Journal of Hepatology

110

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Background/Aims-The underlying mechanisms of steatosis, the first stage of non-alcoholic fatty liver disease (NAFLD) that is characterized by the accumulation of lipids in hepatocytes, remain unclear. Our study aimed to investigate the hypothesis that cigarette smoke is known to change circulating lipid profiles and thus may also contribute to the accumulation of lipids in the liver.Methods-Mice and cultured hepatocytes were exposed to sidestream whole smoke (SSW), a major component of "second-hand" smoke and a variety of cellular and molecular approaches were used to study the effects of cigarette smoke on lipid metabolism.Results-SSW increases lipid accumulation in hepatocytes by modulating the activity of 5′-AMP-activated protein kinase (AMPK) and sterol response element binding protein-1 (SREBP-1), two critical molecules involved in lipid synthesis. SSW causes dephosphorylation/ inactivation of AMPK, which contributes to increased activation of SREBP-1. These changes of activity lead to accumulation of triglycerides in hepatocytes.Conclusion-These novel findings are important because they point to another risk factor of smoking, i.e., that of contributing to NAFLD. In addition, our results showing that both AMPK and SREBP are critically involved in these effects of smoke point to the potential use of these molecules as targets for treatment of cigarette smoke-induced metabolic diseases.

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Section: Discussionmentioning

confidence: 76%

Second-hand smoke stimulates lipid accumulation in the liver by modulating AMPK and SREBP-1

Shyy

Martins‐Green

2009

Journal of Hepatology

110

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“…After defrosting, the cells were divided into three parts (comets, AMP kinase, cytokines) consisting of 3 portions each (130-150×10 3 cells per portion) which were denoted as control, estradiol 10 -8 M, and estradiol 10 -5 M. The samples were incubated with estradiol for 60 min at 37 o C. Analysis of comets (as a DNA injury marker, including the estrogen-induced injury [13]) and their tails was carried out as described previously [12]. The expression of AMP kinase (enzyme sensitive to glucose and estrogens [9]) in mononuclears was evaluated by Western blot with polyclonal antibodies to phosphorylated AMP kinase (Phospho-AMPK, Thr172, Cell Signaling) in 1:1000 dilution according to the instruction [11] (Fig. 1).…”

Section: Methodsmentioning

confidence: 99%

Evaluation of the Proportion of Hormonal and Progenotoxic Effects of Estrogens and Glucose in Cancer Patients

et al. 2010

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he progenotoxic (G, generation of reactive oxygen forms in mononuclears) and hormonal (H, reactive insulinemia) effects of oral glucose, on the one hand, and the same effects of estradiol (10(-8)and 10(-5)M) in vitro on blood mononuclears (G: by comet tail length; H: by expression of AMP kinase and TNF and IL-6 secretion), on the other, were compared with consideration for the concepts on endocrine genotoxic switch-over in patients with breast cancer and endometrial cancer in remission. Coculturing of mononuclears with estradiol in general led to an increase in comet tail and was associated with a trend to more intense expression of AMP kinase and IL-6 secretion. The reaction to estradiol (primarily in a concentration of 10(-8)M) evaluated by the expression of AMP kinase and TNF secretion was more intensive than the reaction evaluated by comet tail lengths or by percentage of cells with comets in women with predominating progenotoxic effect of glucose vs. hormonal effect. This fact can be used as a landmark in search for means for optimization of the status and proportion of effects in the estrogen and glucose systems.

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“…Measurements of plasma levels of reduced glutathione and salivary levels of IgA. Plasma reduced glutathione ([GSH]plasma) and salivary IgA (sIgA) levels were measured as described previously (32,33) via commercially available ELISA using anti-GSH capture antibodies and horseradish peroxidase (HRP)-conjugated secondary antibodies for [GSH]plasma or anti-IgA capture antibodies and HRP-conjugated secondary antibodies for sIgA [Calbiochem Biosciences (Merck), Nottingham, UK]. Saliva samples were collected from a salivette containing a cotton pad placed under the tongue for 2 min, and the cotton pad was centrifuged (300 g for 2 min) to yield liquid saliva.…”

Section: Summary Of the 8-wk Training Programmentioning

confidence: 99%

Exercise-associated generation of PPARγ ligands activates PPARγ signaling events and upregulates genes related to lipid metabolism

Thomas

Davies

Moir

et al. 2012

Journal of Applied Physiology

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The aim of the present study was to test the hypotheses that exercise is associated with generation of peroxisome proliferator-activated receptor-γ (PPARγ) ligands in the plasma and that this may activate PPARγ signaling within circulating monocytes, thus providing a mechanism to underpin the exercise-induced antiatherogenic benefits observed in previous studies. A cohort of healthy individuals undertook an 8-wk exercise-training program; samples were obtained before (Pre) and after (Post) standardized submaximal exercise bouts (45 min of cycling at 70% of maximal O(2) uptake, determined at baseline) at weeks 0, 4, and 8. Addition of plasma samples to PPARγ response element (PPRE)-luciferase reporter gene assays showed increased PPARγ activity following standardized exercise bouts (Post/Pre = 1.23 ± 0.10 at week 0, P < 0.05), suggesting that PPARγ ligands were generated during exercise. However, increases in PPARγ/PPRE-luciferase activity in response to the same standardized exercise bout were blunted during the training program (Post/Pre = 1.18 ± 0.14 and 1.10 ± 0.10 at weeks 4 and 8, respectively, P > 0.05 for both), suggesting that the relative intensity of the exercise may affect PPARγ ligand generation. In untrained individuals, specific transient increases in monocyte expression of PPARγ-regulated genes were observed within 1.5-3 h of exercise (1.7 ± 0.4, 2.6 ± 0.4, and 1.4 ± 0.1 fold for CD36, liver X receptor-α, and ATP-binding cassette subfamily A member 1, respectively, P < 0.05), with expression returning to basal levels within 24 h. In contrast, by the end of the exercise program, expression at the protein level of PPARγ target genes had undergone sustained increases that were not associated with an individual exercise bout (e.g., week 8 Pre/week 0 Pre = 2.79 ± 0.61 for CD36, P < 0.05). Exercise is known to upregulate PPARγ-controlled genes to induce beneficial effects in skeletal muscle (e.g., mitochondrial biogenesis and aerobic respiration). We suggest that parallel exercise-induced benefits may occur in monocytes, as monocyte PPARγ activation has been linked to beneficial antidiabetic effects (e.g., exercise-induced upregulation of monocytic PPARγ-controlled genes is associated with reverse cholesterol transport and anti-inflammatory effects). Thus, exercise-triggered monocyte PPARγ activation may constitute an additional rationale for prescribing exercise to type 2 diabetes patients.

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AMPK inactivation in mononuclear cells: a potential intracellular mechanism for exercise-induced immunosuppression

Cited by 12 publications

References 27 publications

Second-hand smoke stimulates lipid accumulation in the liver by modulating AMPK and SREBP-1

Second-hand smoke stimulates lipid accumulation in the liver by modulating AMPK and SREBP-1

Evaluation of the Proportion of Hormonal and Progenotoxic Effects of Estrogens and Glucose in Cancer Patients

Exercise-associated generation of PPARγ ligands activates PPARγ signaling events and upregulates genes related to lipid metabolism

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