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| 4. |
- Zakharova, AN, et al.
(författare)
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Treadmill Training Effect on the Myokines Content in Skeletal Muscles of Mice With a Metabolic Disorder Model
- 2021
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Ingår i: Frontiers in physiology. - : Frontiers Media SA. - 1664-042X. ; 12, s. 709039-
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Tidskriftsartikel (refereegranskat)abstract
- The effect of treadmill training loads on the content of cytokines in mice skeletal muscles with metabolic disorders induced by a 16 week high fat diet (HFD) was studied. The study included accounting the age and biorhythmological aspects. In the experiment, mice were used at the age of 4 and 32 weeks, by the end of the experiment—respectively 20 and 48 weeks. HFD feeding lasted 16 weeks. Treadmill training were carried out for last 4 weeks six times a week, the duration 60 min and the speed from 15 to 18 m/min. Three modes of loading were applied. The first subgroup was subjected to stress in the morning hours (light phase); the second subgroup was subjected to stress in the evening hours (dark phase); the third subgroup was subjected to loads in the shift mode (the first- and third-weeks treadmill training was used in the morning hours, the second and fourth treadmill training was used in the evening hours). In 20-week-old animals, the exercise effect does not depend on the training regime, however, in 48-week-old animals, the decrease in body weight in mice with the shift training regime was more profound. HFD affected muscle myokine levels. The content of all myokines, except for LIF, decreased, while the concentration of CLCX1 decreased only in young animals in response to HFD. The treadmill training caused multidirectional changes in the concentration of myokines in muscle tissue. The IL-6 content changed most profoundly. These changes were observed in all groups of animals. The changes depended to the greatest extent on the training time scheme. The effect of physical activity on the content of IL-15 in the skeletal muscle tissue was observed mostly in 48-week-old mice. In 20-week-old animals, physical activity led to an increase in the concentration of LIF in muscle tissue when applied under the training during the dark phase or shift training scheme. In the HFD group, this effect was significantly more pronounced. The content of CXCL1 did not change with the use of treadmill training in almost all groups of animals. Physical activity, introduced considering circadian rhythms, is a promising way of influencing metabolic processes both at the cellular and systemic levels, which is important for the search for new ways of correcting metabolic disorders.
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- Al-Khalili, L, et al.
(författare)
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MEF2 activation in differentiated primary human skeletal muscle cultures requires coordinated involvement of parallel pathways
- 2004
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Ingår i: American journal of physiology. Cell physiology. - : American Physiological Society. - 0363-6143 .- 1522-1563. ; 286:6, s. C1410-C1416
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Tidskriftsartikel (refereegranskat)abstract
- The myocyte enhancer factor (MEF)2 transcription factor is important for development of differentiated skeletal muscle. We investigated the regulation of MEF2 DNA binding in differentiated primary human skeletal muscle cells and isolated rat skeletal muscle after exposure to various stimuli. MEF2 DNA binding activity in nonstimulated (basal) muscle cultures was almost undetectable. Exposure of cells for 20 min to 120 nM insulin, 0.1 and 1.0 mM hydrogen peroxide, osmotic stress (400 mM mannitol), or 1.0 mM 5-aminoimidazole-4-carboxamide-1-β- d-ribofuranoside (AICAR) led to a profound increase in MEF2 DNA binding. To study signaling pathways mediating MEF2 activity, we preincubated human skeletal muscle cell cultures or isolated rat epitrochlearis muscles with inhibitors of p38 mitogen-activated protein kinase (MAPK) (10 μM SB-203580), MEK1 (50 μM PD-98059), PKC (1 and 10 μM GF109203X), phosphatidylinositol (PI) 3-kinase (10 μM LY-294002), or AMP-activated protein kinase (AMPK; 20 μM compound C). All stimuli resulted primarily in activation of MEF2D DNA binding. Exposure of cells to osmotic or oxidative stress increased MEF2 DNA binding via pathways that were completely blocked by MAPK inhibitors and partially blocked by inhibitors of PKC, PI 3-kinase, and AMPK. In epitrochlearis muscle, MAPK inhibitors blocked contraction but not AICAR-mediated MEF2 DNA binding. Thus activation of MEF2 in skeletal muscle is regulated via parallel intracellular signaling pathways in response to insulin, cellular stress, or activation of AMPK.
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- Benziane, B, et al.
(författare)
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AMP-activated protein kinase activator A-769662 is an inhibitor of the Na(+)-K(+)-ATPase
- 2009
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Ingår i: American journal of physiology. Cell physiology. - : American Physiological Society. - 1522-1563 .- 0363-6143. ; 297:6, s. C1554-C1566
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Tidskriftsartikel (refereegranskat)abstract
- Muscle contraction and metabolic stress are potent activators of AMP-activated protein kinase (AMPK). AMPK restores energy balance by activating processes that produce energy while inhibiting those that consume energy. The role of AMPK in the regulation of active ion transport is unclear. Our aim was to determine the effect of the AMPK activator A-769662 on Na+-K+-ATPase function in skeletal muscle cells. Short-term incubation of differentiated rat L6 myotubes with 100 μM A-769662 increased AMPK and acetyl-CoA carboxylase (ACC) phosphorylation in parallel with decreased Na+-K+-ATPase α1-subunit abundance at the plasma membrane and ouabain-sensitive86Rb+uptake. Notably, the effect of A-769662 on Na+-K+-ATPase was similar in muscle cells that do not express AMPK α1- and α2-catalytic subunits. A-769662 directly inhibits the α1-isoform of the Na+-K+-ATPase, purified from rat and human kidney cells in vitro with IC5057 μM and 220 μM, respectively. Inhibition of the Na+-K+-ATPase by 100 μM ouabain decreases sodium pump activity and cell surface abundance, similar to the effect of A-769662, without affecting AMPK and ACC phosphorylation. In conclusion, the AMPK activator A-769662 inhibits Na+-K+-ATPase activity and decreases the sodium pump cell surface abundance in L6 skeletal muscle cells. The effect of A-769662 on sodium pump is due to direct inhibition of the Na+-K+-ATPase activity, rather than AMPK activation. This AMPK-independent effect on Na+-K+-ATPase calls into question the use of A-769662 as a specific AMPK activator for metabolic studies.
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- Benziane, B, et al.
(författare)
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Divergent cell signaling after short-term intensified endurance training in human skeletal muscle
- 2008
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Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 295:6, s. E1427-E1438
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Tidskriftsartikel (refereegranskat)abstract
- Endurance training represents one extreme in the continuum of skeletal muscle plasticity. The molecular signals elicited in response to acute and chronic exercise and the integration of multiple intracellular pathways are incompletely understood. We determined the effect of 10 days of intensified cycle training on signal transduction in nine inactive males in response to a 1-h acute bout of cycling at the same absolute workload (164 ± 9 W). Muscle biopsies were taken at rest and immediately and 3 h after the acute exercise. The metabolic signaling pathways, including AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR), demonstrated divergent regulation by exercise after training. AMPK phosphorylation increased in response to exercise (∼16-fold; P < 0.05), which was abrogated posttraining ( P < 0.01). In contrast, mTOR phosphorylation increased in response to exercise (∼2-fold; P < 0.01), which was augmented posttraining ( P < 0.01) in the presence of increased mTOR expression ( P < 0.05). Exercise elicited divergent effects on mitogen-activated protein kinase (MAPK) pathways after training, with exercise-induced extracellular signal-regulated kinase (ERK) 1/2 phosphorylation being abolished ( P < 0.01) and p38 MAPK maintained. Finally, calmodulin kinase II (CaMKII) exercise-induced phosphorylation and activity were maintained ( P < 0.01), despite increased expression (∼2-fold; P < 0.05). In conclusion, 10 days of intensified endurance training attenuated AMPK, ERK1/2, and mTOR, but not CaMKII and p38 MAPK signaling, highlighting molecular pathways important for rapid functional adaptations and maintenance in response to intensified endurance exercise and training.
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| 15. |
- Benziane, B, et al.
(författare)
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Effect of exercise and training on phospholemman phosphorylation in human skeletal muscle
- 2011
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Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 301:3, s. E456-E466
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Tidskriftsartikel (refereegranskat)abstract
- Phospholemman (PLM, FXYD1) is a partner protein and regulator of the Na+-K+-ATPase (Na+-K+pump). We explored the impact of acute and short-term training exercise on PLM physiology in human skeletal muscle. A group of moderately trained males ( n = 8) performed a 1-h acute bout of exercise by utilizing a one-legged cycling protocol. Muscle biopsies were taken from vastus lateralis at 0 and 63 min (non-exercised leg) and 30 and 60 min (exercised leg). In a group of sedentary males ( n = 9), we determined the effect of a 10-day intense aerobic cycle training on Na+-K+-ATPase subunit expression, PLM phosphorylation, and total PLM expression as well as PLM phosphorylation in response to acute exercise (1 h at ∼72% V̇o2peak). Biopsies were taken at rest, immediately following, and 3 h after an acute exercise bout before and at the conclusion of the 10-day training study. PLM phosphorylation was increased both at Ser63and Ser68immediately after acute exercise (75%, P < 0.05, and 30%, P < 0.05, respectively). Short-term training had no adaptive effect on PLM phosphorylation at Ser63and Ser68, nor was the total amount of PLM altered posttraining. The protein expressions of α1-, α2-,and β1-subunits of Na+-K+-ATPase were increased after training (113%, P < 0.05, 49%, P < 0.05, and 27%, P < 0.05, respectively). Whereas an acute bout of exercise increased the phosphorylation of PKCα/βII on Thr638/641pre- and posttraining, phosphorylation of PKCζ/λ on Thr403/410was increased in response to acute exercise only after the 10-day training. In conclusion, we show that only acute exercise, and not short-term training, increases phosphorylation of PLM on Ser63and Ser68, and data from one-legged cycling indicate that this effect of exercise on PLM phosphorylation is not due to systemic factors. Our results provide evidence that phosphorylation of PLM may play a role in the acute regulation of the Na+-K+-ATPase response to exercise.
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| 16. |
- Benziane, B, et al.
(författare)
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Frontiers: skeletal muscle sodium pump regulation: a translocation paradigm
- 2008
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Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 295:3, s. E553-E558
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Tidskriftsartikel (refereegranskat)abstract
- The skeletal muscle sodium pump plays a major role in the removal of K+ions from the circulation postprandial, or after a physical activity bout, thereby preventing the development of hyperkalemia and fatigue. Insulin and muscle contractions stimulate Na+-K+-ATPase activity in skeletal muscle, at least partially via translocation of sodium pump units to the plasma membrane from intracellular stores. The molecular mechanism of this phenomenon is poorly understood. Due to the contradictory reports in the literature, the very existence of the translocation of Na+-K+-ATPase to the skeletal muscle cell surface is questionable. This review summarizes more than 30 years work on the skeletal muscle sodium pump translocation paradigm. Furthermore, the methodological caveats of major approaches to study the sodium pump translocation in skeletal muscle are discussed. An understanding of the molecular regulation of Na+-K+-ATPase in skeletal muscle will have important clinical implications for the understanding of the development of complications associated with the metabolic syndrome, such as cardiovascular diseases or increased muscle fatigue in diabetic patients.
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| 19. |
- Borg, ML, et al.
(författare)
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Modified UCN2 Peptide Acts as an Insulin Sensitizer in Skeletal Muscle of Obese Mice
- 2019
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 68:7, s. 1403-1414
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Tidskriftsartikel (refereegranskat)abstract
- The neuropeptide urocortin 2 (UCN2) and its receptor corticotropin-releasing hormone receptor 2 (CRHR2) are highly expressed in skeletal muscle and play a role in regulating energy balance and glucose metabolism. We investigated a modified UCN2 peptide as a potential therapeutic agent for the treatment of obesity and insulin resistance, with a specific focus on skeletal muscle. High-fat–fed mice (C57BL/6J) were injected daily with a PEGylated UCN2 peptide (compound A) at 0.3 mg/kg subcutaneously for 14 days. Compound A reduced body weight, food intake, whole-body fat mass, and intramuscular triglycerides compared with vehicle-treated controls. Furthermore, whole-body glucose tolerance was improved by compound A treatment, with increased insulin-stimulated Akt phosphorylation at Ser473 and Thr308 in skeletal muscle, concomitant with increased glucose transport into extensor digitorum longus and gastrocnemius muscle. Mechanistically, this is linked to a direct effect on skeletal muscle because ex vivo exposure of soleus muscle from chow-fed lean mice to compound A increased glucose transport and insulin signaling. Moreover, exposure of GLUT4-Myc–labeled L6 myoblasts to compound A increased GLUT4 trafficking. Our results demonstrate that modified UCN2 peptides may be efficacious in the treatment of type 2 diabetes by acting as an insulin sensitizer in skeletal muscle.
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| 23. |
- Bustamante, M, et al.
(författare)
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Insulin potentiates AVP-induced AQP2 expression in cultured renal collecting duct principal cells
- 2005
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Ingår i: American journal of physiology. Renal physiology. - : American Physiological Society. - 1931-857X .- 1522-1466. ; 288:2, s. F334-F344
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Tidskriftsartikel (refereegranskat)abstract
- In the renal collecting duct (CD), water reabsorption depends on the presence of aquaporin-2 (AQP2) in the apical membrane of principal cells. AQP2 expression and subcellular repartition are under the control of AVP. Some pieces of experimental evidence indicate that additional hormonal factors, including insulin, may also control AQP2 expression and thereby CD water permeability. We have previously shown that AVP induces endogenous AQP2 expression in cultured mouse mpkCCDcl4CD principal cells ( 23 ). In the present study, we investigated the effect of insulin on AQP2 expression in mpkCCDcl4cells. Addition of insulin to the basal medium of cells grown on filters slightly increased AQP2 mRNA and protein expression, whereas insulin potentiated the effect of AVP. The potentiation of AVP-induced AQP2 expression by insulin was abolished by actinomycin D, a transcriptional inhibitor. Analysis of AQP2 protein expression under conditions of AVP washout and/or in the presence of chloroquine, a lysosomal degradation inhibitor, revealed that insulin did not significantly alter AQP2 protein degradation. Inhibition of ERK, p38 kinase, and phosphatidylinositol 3′-kinase (PI 3-kinase) activities prevented the insulin-induced stimulation of AQP2 expression, whereas inhibition of PKC has no effect. Taken together, our results indicate that insulin increased AQP2 protein expression mostly through increased AQP2 mRNA levels in cultured mpkCCDcl4cells. This effect most likely relies on increased AQP2 gene transcription in response to MAPK and PI 3-kinase activation.
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