Divergent cell signaling after short-term intensified endurance training in human skeletal muscle

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 ( approximately 16-fold; P < 0.05), which was abrogated posttraining (P < 0.01). In contrast, mTOR phosphorylation increased in response to exercise ( approximately 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 ( approximately 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.

PGC-1α-mediated changes in phospholipid profiles of exercise-trained skeletal muscle

“…Exercise training stimulates physiological adaptation in skeletal muscle by affecting contractile activity ( 12,13 ), mitochondrial function ( 14 ), metabolic regulation ( 15 ), intracellular signaling ( 16 ), and transcriptional responses ( 17,18 ). Peroxisome proliferator-activated receptor ␥ coactivator 1 ␣ (PGC-1 ␣ ), identifi ed as nuclear receptor coactivator, is expressed in brown adipose tissue, skeletal muscle, heart, kidney, and brain, and is markedly upregulated in brown adipose tissue and skeletal muscle after acute exposure to cold stress ( 19 ).…”

Effect of N-acetylcysteine infusion on exercise-induced modulation of insulin sensitivity and signaling pathways in human skeletal muscle

“…Graded exercise tests were conducted to determine V O2peak using a previously described protocol (2). Briefly, the test started at 100 W (50 W for female) and increased initially by 50 and 25 W thereafter every 2.5 min.…”

“…Protein concentration of the resulting supernatant was determined using a commercially available BCA kit (Thermo Scientific, Waltham, MA), as described previously (2). Aliquots of the muscle lysates were diluted with Laemmli (18).…”

The Emerging Role of p53 in Exercise Metabolism

“…These kinases, acting alone or in combination with each other, can subsequently activate downstream transcription factors and co-activators [19] that exert regulatory roles in co-ordinating the expression of both nuclear and mitochondrial-encoded proteins. Broadly speaking, activation of the aforementioned kinases is dependent on exercise modality [20], intensity [19], duration [21,22], training history [23], training status [24] and nutrient availability [25]. When taken together, these data provide an insight as to the potential molecular mechanisms underpinning some of the well-known training principles, in that training programs should ensure a continual alteration in workload and manipulation of energy provision in order to repeatedly stimulate the necessary signalling pathways required to support sustained muscle adaptation.…”