Time course of IL-15 expression after acute resistance exercise in trained rats: effect of diabetes and skeletal muscle phenotype

ABSTRACTRibosomes are the macromolecular engines of protein synthesis. Skeletal muscle ribosome biogenesis is stimulated by exercise, but the contribution of ribosomal DNA (rDNA) copy number and methylation to exercise-induced rDNA transcription is unclear. To investigate the genetic and epigenetic regulation of ribosome biogenesis with exercise, a time course of skeletal muscle biopsies was obtained from 30 participants (18 men and 12 women; 31 ±8 yrs, 25 ±4 kg/m2) at rest and 30 min, 3h, 8h, and 24h after acute endurance (n=10, 45 min cycling, 70% VO2max) or resistance exercise (n=10, 4 x 7 x 2 exercises); 10 control participants underwent biopsies without exercise. rDNA transcription and dosage were assessed using qPCR and whole genome sequencing. rDNA promoter methylation was investigated using massARRAY EpiTYPER, and global rDNA CpG methylation was assessed using reduced-representation bisulfite sequencing. Ribosome biogenesis and MYC transcription were associated with resistance but not endurance exercise, indicating preferential up-regulation during hypertrophic processes. With resistance exercise, ribosome biogenesis was associated with rDNA gene dosage as well as epigenetic changes in enhancer and non-canonical MYC-associated areas in rDNA, but not the promoter. A mouse model of in vivo metabolic RNA labeling and genetic myonuclear fluorescent labeling validated the effects of an acute hypertrophic stimulus on ribosome biogenesis and Myc transcription, and corroborated rDNA enhancer and Myc-associated methylation alterations specifically in myonuclei. This study provides the first information on skeletal muscle genetic and rDNA gene-wide epigenetic regulation of ribosome biogenesis in response to exercise, revealing novel roles for rDNA dosage and CpG methylation.GRAPHICAL ABSTRACT

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Transient transcriptional events in human skeletal muscle at the outset of concentric resistance exercise training

Journal of Applied Physiology ◽

10.1152/japplphysiol.00426.2013 ◽

2014 ◽

Vol 116 (1) ◽

pp. 113-125 ◽

Cited By ~ 33

Author(s):

A. J. Murton ◽

R. Billeter ◽

F. B. Stephens ◽

S. G. Des Etages ◽

F. Graber ◽

...

Keyword(s):

Skeletal Muscle ◽

Resistance Exercise ◽

Muscle Damage ◽

Time Course ◽

Human Skeletal Muscle ◽

Vastus Lateralis ◽

Transcriptional Response ◽

Physiological Adaptation ◽

Multiple Time ◽

Αb Crystallin

We sought to ascertain the time course of transcriptional events that occur in human skeletal muscle at the outset of resistance exercise (RE) training in RE naive individuals and determine whether the magnitude of response was associated with exercise-induced muscle damage. Sixteen RE naive men were recruited; eight underwent two sessions of 5 × 30 maximum isokinetic knee extensions (180°/s) separated by 48 h. Muscle biopsies of the vastus lateralis, obtained from different sites, were taken at baseline and 24 h after each exercise bout. Eight individuals acted as nonexercise controls with biopsies obtained at the same time intervals. Transcriptional changes were assessed by microarray and protein levels of heat shock protein (HSP) 27 and αB-crystallin in muscle cross sections by immunohistochemistry as a proxy measure of muscle damage. In control subjects, no probe sets were significantly altered (false discovery rate < 0.05), and HSP27 and αB-crystallin protein remained unchanged throughout the study. In exercised subjects, significant intersubject variability following the initial RE bout was observed in the muscle transcriptome, with greatest changes occurring in subjects with elevated HSP27 and αB-crystallin protein. Following the second bout, the transcriptome response was more consistent, revealing a cohort of probe sets associated with immune activation, the suppression of oxidative metabolism, and ubiquitination, as differentially regulated. The results reveal that the initial transcriptional response to RE is variable in RE naive volunteers, potentially associated with muscle damage and unlikely to reflect longer term adaptations to RE training. These results highlight the importance of considering multiple time points when determining the transcriptional response to RE and associated physiological adaptation.

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Time course of molecular responses of human skeletal muscle to acute bouts of resistance exercise

Scandinavian Journal of Medicine and Science in Sports ◽

10.1111/j.1600-0838.2005.453_2.x ◽

2005 ◽

Vol 15 (2) ◽

pp. 135-136 ◽

Cited By ~ 1

Author(s):

C. S. Bickel ◽

J. Slade ◽

E. Mahoney ◽

F. Haddad ◽

G. A. Dudley ◽

...

Keyword(s):

Skeletal Muscle ◽

Resistance Exercise ◽

Time Course ◽

Human Skeletal Muscle ◽

Molecular Responses

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Time course of molecular responses of human skeletal muscle to acute bouts of resistance exercise

Journal of Applied Physiology ◽

10.1152/japplphysiol.00895.2004 ◽

2005 ◽

Vol 98 (2) ◽

pp. 482-488 ◽

Cited By ~ 111

Author(s):

C. Scott Bickel ◽

Jill Slade ◽

Ed Mahoney ◽

Fadia Haddad ◽

Gary A. Dudley ◽

...

Keyword(s):

Skeletal Muscle ◽

Resistance Exercise ◽

Time Course ◽

Binding Protein ◽

Neuromuscular Electrical Stimulation ◽

Exercise Bout ◽

High Temporal Resolution ◽

Igf I ◽

Igf Binding ◽

Igf Binding Protein

Resistance exercise (RE) training, designed to induce hypertrophy, strives for optimal activation of anabolic and myogenic mechanisms to increase myofiber size. Clearly, activation of these mechanisms must precede skeletal muscle growth. Most mechanistic studies of RE have involved analysis of outcome variables after many training sessions. This study measured molecular level responses to RE on a scale of hours to establish a time course for the activation of myogenic mechanisms. Muscle biopsy samples were collected from nine subjects before and after acute bouts of RE. The response to a single bout was assessed at 12 and 24 h postexercise. Further samples were obtained 24 and 72 h after a second exercise bout. RE was induced by neuromuscular electrical stimulation to generate maximal isometric contractions in the muscle of interest. A single RE bout resulted in increased levels of mRNA for IGF binding protein-4 (84%), MyoD (83%), myogenin (∼3-fold), cyclin D1 (50%), and p21-Waf1 (16-fold), and a transient decrease in IGF-I mRNA (46%). A temporally conserved, significant correlation between myogenin and p21 mRNA was observed ( r = 0.70, P ≤ 0.02). The mRNAs for mechano-growth factor, IGF binding protein-5, and the IGF-I receptor were unchanged by RE. Total skeletal muscle RNA was increased 72 h after the second serial bout of RE. These results indicate that molecular adaptations of skeletal muscle to loading respond in a very short time. This approach should provide insights on the mechanisms that modulate adaptation to RE and may be useful in evaluating RE training protocol variables with high temporal resolution.

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Coordinated alpha-crystallin B phosphorylation and desmin expression indicate adaptation and deadaptation to resistance exercise-induced loading in human skeletal muscle

AJP Cell Physiology ◽

10.1152/ajpcell.00087.2020 ◽

2020 ◽

Vol 319 (2) ◽

pp. C300-C312

Author(s):

Daniel Jacko ◽

Käthe Bersiner ◽

Oliver Schulz ◽

Axel Przyklenk ◽

Fabian Spahiu ◽

...

Keyword(s):

Skeletal Muscle ◽

Resistance Exercise ◽

Time Course ◽

Protein Unfolding ◽

Essential Role ◽

Group Differences ◽

Structural Stabilization ◽

Alpha Crystallin ◽

Serine 59 ◽

Exercise Induced

Skeletal muscle is a target of contraction-induced loading (CiL), leading to protein unfolding or cellular perturbations, respectively. While cytoskeletal desmin is responsible for ongoing structural stabilization, in the immediate response to CiL, alpha-crystallin B (CRYAB) is phosphorylated at serine 59 (pCRYABS59) by P38, acutely protecting the cytoskeleton. To reveal adaptation and deadaptation of these myofibrillar subsystems to CiL, we examined CRYAB, P38, and desmin regulation following resistance exercise at diverse time points of a chronic training period. Mechanosensitive JNK phosphorylation (pJNKT183/Y185) was determined to indicate the presence of mechanical components in CiL. Within 6 wk, subjects performed 13 resistance exercise bouts at the 8–12 repetition maximum, followed by 10 days detraining and a final 14th bout. Biopsies were taken at baseline and after the 1st, 3rd, 7th, 10th, 13th, and 14th bout. To assess whether potential desensitization to CiL can be mitigated, one group trained with progressive and a second with constant loading. As no group differences were found, all subjects were combined for statistics. Total and phosphorylated P38 was not regulated over the time course. pCRYABS59 and pJNKT183/Y185 strongly increased following the unaccustomed first bout. This exercise-induced pCRYABS59/pJNKT183/Y185 increase disappeared with the 10th until 13th bout. As response to the detraining period, the 14th bout led to a renewed increase in pCRYABS59. Desmin content followed pCRYABS59 inversely, i.e., was up- when pCRYABS59 was downregulated and vice versa. In conclusion, the pCRYABS59 response indicates increase and decrease in resistance to CiL, in which a reinforced desmin network could play an essential role by structurally stabilizing the cells.

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UPTAKE OF OXYTOCIN IN TISSUES AFTER INTRAVENOUS ADMINISTRATION OF TRITIATED OXYTOCIN IN RATS

Acta Endocrinologica ◽

10.1530/acta.0.0610432 ◽

1969 ◽

Vol 61 (3) ◽

pp. 432-440 ◽

Cited By ~ 7

Author(s):

Ingvar Sjöholm ◽

Gunnar Rydén

Keyword(s):

Skeletal Muscle ◽

Distribution Pattern ◽

Intravenous Injection ◽

Intravenous Administration ◽

Time Course ◽

Tritiated Water ◽

Preferential Distribution ◽

Time Period ◽

Initial Uptake

ABSTRACT The distribution of oxytocin in the kidneys, liver, uterus and skeletal muscle of the rat was followed during 10 min after intravenous injection of tritium labelled oxytocin. Oxytocin was found to be taken up and degraded mainly in the kidneys and the liver. After 150 seconds no intact oxytocin could be detected in these organs. The time course of the distribution of the radioactivity in the liver and the skeletal muscle showed no noteworthy characteristics, whereas a different course was found in the kidneys and in the uterus. In the kidneys, the radioactivity increased continuously from 60 to 200 seconds after the injection, indicating an accumulation of oxytocin or its metabolites in the kidneys. In the uterus a high initial uptake was observed, followed by a decrease of the radioactivity from 60 to 100 seconds after the injection. This distribution pattern was specific to oxytocin, since the uptake of tritiated tyrosine and tritiated water was almost constant during the same time period. These findings may indicate a preferential distribution of oxytocin to the uterus.

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