Effects of age and exercise on inflammatory cytokines, HSP70 and HSP90 gene expression and protein content in Standardbred horses

2018 ◽  
Vol 14 (1) ◽  
pp. 27-46 ◽  
Author(s):  
R.C. Avenatti ◽  
K.H. McKeever ◽  
D.W. Horohov ◽  
K. Malinowski
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Whole Blood ◽  
Plasma Cortisol ◽  
Acute Exercise ◽  
Submaximal Exercise ◽  
Hsp70 Expression ◽  
Post Exercise ◽  
Hsp90 Expression ◽  
Young Horses

We hypothesised that the cortisol response to acute exercise, markers of oxidative stress, expression of inflammatory cytokines, heat shock protein (HSP)70 and HSP90 expression in whole blood and skeletal muscle, and HSP70 and HSP90 protein concentrations in skeletal muscle are altered by age and in response to acute submaximal exercise in horses. Young (n=6; 5.5±2.8 year) and aged (n=6; 22.6±2.25 year) unconditioned Standardbred mares underwent an acute submaximal exercise test. Blood samples were collected and analysed for plasma cortisol and malondialdehyde (MDA) concentrations, and for cytokine and HSP gene expression pre- and post-exercise. Gluteus medius biopsies were obtained for analysis of cytokine and HSP gene expression pre- and at 0, 4, 24 and 48 h post-exercise. Data were analysed for main effects using a two-way ANOVA for repeated measures. Post-hoc comparisons of means were conducted using Student-Neuman-Keuls for pair-wise multiple comparisons where appropriate. Acute submaximal exercise increased plasma cortisol concentration in both young and aged mares, and the duration of the post-exercise rise in cortisol was altered in aged horses. Plasma MDA concentration and expression of tumour necrosis factor-α (TNF-α) and interleukin (IL)-6 were unchanged in blood and muscle. Exercise increased IL-1β expression in whole blood of young and aged mares, with young mares having greater exercise-induced expression at 2 (P<0.001) and 4 (P=0.019) h post-exercise. Both young and aged horses had increased HSP70 expression in whole blood following acute exercise, with young horses exhibiting 3-fold greater HSP70 expression than aged mares at 2 h post-exercise. HSP90 expression in whole blood following exercise was increased only in young horses. Both young and aged horses had increased HSP90 expression in skeletal muscle following exercise, but there was no difference due to age. However, the timing of HSP70 expression was different between young and aged horses. The age-related changes in cortisol and IL-1β expression following acute submaximal exercise can have implications for energy homeostasis and the adaption to such disturbances at a cellular and whole animal level. Quantification of HSP expression in whole blood may be a useful biomarker, with implications for cellular adaptation and survival in aged horses.

scholarly journals Role of GDF15 in active lifestyle induced metabolic adaptations and acute exercise response in mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Carla Igual Gil ◽  
Mario Ost ◽  
Juliane Kasch ◽  
Sara Schumann ◽  
Sarah Heider ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Acute Exercise ◽  
Treadmill Running ◽  
Exercise Stress ◽  
Metabolic Phenotype ◽  
Obese Mice ◽  
Active Lifestyle ◽  
Post Exercise ◽  
Stress Markers

AbstractPhysical activity is an important contributor to muscle adaptation and metabolic health. Growth differentiation factor 15 (GDF15) is established as cellular and nutritional stress-induced cytokine but its physiological role in response to active lifestyle or acute exercise is unknown. Here, we investigated the metabolic phenotype and circulating GDF15 levels in lean and obese male C57Bl/6J mice with long-term voluntary wheel running (VWR) intervention. Additionally, treadmill running capacity and exercise-induced muscle gene expression was examined in GDF15-ablated mice. Active lifestyle mimic via VWR improved treadmill running performance and, in obese mice, also metabolic phenotype. The post-exercise induction of skeletal muscle transcriptional stress markers was reduced by VWR. Skeletal muscle GDF15 gene expression was very low and only transiently increased post-exercise in sedentary but not in active mice. Plasma GDF15 levels were only marginally affected by chronic or acute exercise. In obese mice, VWR reduced GDF15 gene expression in different tissues but did not reverse elevated plasma GDF15. Genetic ablation of GDF15 had no effect on exercise performance but augmented the post exercise expression of transcriptional exercise stress markers (Atf3, Atf6, and Xbp1s) in skeletal muscle. We conclude that skeletal muscle does not contribute to circulating GDF15 in mice, but muscle GDF15 might play a protective role in the exercise stress response.

scholarly journals Promoter-specific regulation of PPARGC1A gene expression in human skeletal muscle

2015 ◽  
Vol 55 (2) ◽  
pp. 159-168 ◽  
Author(s):  
Daniil V Popov ◽  
Evgeny A Lysenko ◽  
Tatiana F Vepkhvadze ◽  
Nadia S Kurochkina ◽  
Pavel A Maknovskii ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Stop Codon ◽  
Constitutive Expression ◽  
Alternative Promoter ◽  
Specific Expression ◽  
Post Exercise ◽  
Specific Regulation ◽  
Intensity Of Exercise

The goal of this study was to identify unknown transcription start sites of thePPARGC1A(PGC-1α) gene in human skeletal muscle and investigate the promoter-specific regulation ofPGC-1αgene expression in human skeletal muscle. Ten amateur endurance-trained athletes performed high- and low-intensity exercise sessions (70 min, 70% or 50%o2max). High-throughput RNA sequencing and exon–exon junction mapping were applied to analyse muscle samples obtained at rest and after exercise.PGC-1αpromoter-specific expression and activation of regulators of PGC-1α gene expression (AMPK, p38 MAPK, CaMKII, PKA and CREB1) after exercise were evaluated using qPCR and western blot. Our study has demonstrated that during post-exercise recovery, human skeletal muscle expresses thePGC-1αgene via two promoters only. As previously described, the additional exon 7a that contains a stop codon was found in all samples. Importantly, only minor levels of other splice site variants were found (and not in all samples). Constitutive expressionPGC-1αgene occurs via the canonical promoter, independent of exercise intensity and exercise-induced increase of AMPKThr172phosphorylation level. Expression ofPGC-1αgene via the alternative promoter is increased of two orders after exercise. This post-exercise expression is highly dependent on the intensity of exercise. There is an apparent association between expression via the alternative promoter and activation of CREB1.

Skeletal muscle metabolic recovery following submaximal exercise in chronic heart failure is limited more by O2 delivery than O2 utilization

2010 ◽  
Vol 118 (3) ◽  
pp. 203-210 ◽  
Author(s):  
Hareld M.C. Kemps ◽  
Jeanine J. Prompers ◽  
Bart Wessels ◽  
Wouter R. De Vries ◽  
Maria L. Zonderland ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Chronic Heart Failure ◽  
Submaximal Exercise ◽  
Daily Activities ◽  
Control Group ◽  
Resonance Spectroscopy ◽  
Post Exercise ◽  
Metabolic Recovery ◽  
O2 Delivery

CHF (chronic heart failure) is associated with a prolonged recovery of skeletal muscle energy stores following submaximal exercise, limiting the ability to perform repetitive daily activities. However, the pathophysiological background of this impairment is not well established. The aim of the present study was to investigate whether muscle metabolic recovery following submaximal exercise in patients with CHF is limited by O2 delivery or O2 utilization. A total of 13 stable CHF patients (New York Heart Association classes II–III) and eight healthy subjects, matched for age and BMI (body mass index), were included. All subjects performed repetitive submaximal dynamic single leg extensions in the supine position. Post-exercise PCr (phosphocreatine) resynthesis was assessed by 31P-MRS (magnetic resonance spectroscopy). NIRS (near-IR spectroscopy) was applied simultaneously, using the rate of decrease in HHb (deoxygenated haemoglobin) as an index of post-exercise muscle re-oxygenation. As expected, PCr recovery was slower in CHF patients than in control subjects (time constant, 47±10 compared with 35±12 s respectively; P=0.04). HHb recovery kinetics were also prolonged in CHF patients (mean response time, 74±41 compared with 44±17 s respectively; P=0.04). In the patient group, HHb recovery kinetics were slower than PCr recovery kinetics (P=0.02), whereas no difference existed in the control group (P=0.32). In conclusion, prolonged metabolic recovery in CHF patients is associated with an even slower muscle tissue re-oxygenation, indicating a lower O2 delivery relative to metabolic demands. Therefore we postulate that the impaired ability to perform repetitive daily activities in these patients depends more on a reduced muscle blood flow than on limitations in O2 utilization.

scholarly journals PL-008 Adaptation of skeletal muscle to aerobic exercise: specific transcriptome response to acute exercise and training

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Daniil Popov ◽  
Pavel Makhnovskii ◽  
Evgeny Lysenko ◽  
Olga Vinogradova
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Circadian Rhythm ◽  
Human Skeletal Muscle ◽  
Acute Exercise ◽  
Aerobic Training ◽  
Contractile Activity ◽  
Training Programme ◽  
Specific Response ◽  
Transcriptome Response

Objective Variety of processes including circadian rhythm and systemic factors affect expression of many genes in skeletal muscle during a day. Therefore, post-exercise gene expression depends on many factors: contractile activity per seas well as circadian rhythm, nerve activity, concentration of different substances in blood, feeding and fasting. In our study, we investigated specific for contractile activity changes in the transcriptome in untrained and trained (after an aerobic training programme) human skeletal muscle. The second goal was to examine effect of aerobic training on gene expression in muscle in basal state. Methods Seven untrained males performed the one-legged knee extension exercise (for 60 min) with the same relative intensity before and after a 2 month aerobic training programme (1 h/day, 5/week). Biopsy samples were taken at rest (basal state, 48 h after the previous exercise), 1 and 4 h after one-legged exercise from m. vastus lateralisof either leg. This approach allowed us to evaluate specific changes in the transcriptome associated with contractile activity. RNA­sequencing (84 samples in total; ~42 million reads/sample) was performed by HiSeq 2500 (Illumina). Results Two months aerobic training increased the aerobic capacity of the knee-extensor muscles (power at anaerobic threshold in incremental one-legged and cycling tests), the maximum rate of ADP-stimulated mitochondrial respiration in permeabilized muscle fibres and amounts of oxidative phosphorylation proteins. After one-legged exercise, expression of many genes was changed in exercised muscle (~1500) as well as in non-exercised muscle (~400). Pronounced changes in gene expression in non-exercised muscle may be associated with many factors, including circadian rhythm (result of GO analysis). To examine transcriptome changes specific for contractile activity, the difference in gene expression between legs was examined. In untrained muscle, one-legged exercise changed expression of ~1200 genes specific for contractile activity at each time point. Despite the same relative intensity of one-legged exercise, transcriptomic response in trained muscle was markedly lower (~300 genes) compare to untrained. We observed a strong overlap between transcriptomic responses (~250 genes) and particularly between enriched transcription factor binding sites in promoters of these genes in untrained and trained muscles. These sets of genes and transcription factors play the key role in adaptation of muscle to contractile activity independently on the level of muscular fitness. Surprisingly, 2 months aerobic training changed the expression of more than 1500 genes in basal state. Noteworthy, these genes demonstrated a small overlap (~200 genes) with genes related to specific response to acute exercise. Moreover, these genes were associated with significantly different biological processes than genes related to specific response to acute exercise. Conclusions Specific for contractile activity changes in the transcriptome in untrained and trained human skeletal muscle were revealed for the first time. After 2 month aerobic training, the specific transcriptome response to acute exercise become much less pronounced. A computational approach reveals common transcription factors important for adaptation of both untrained and trained muscle. We found out that adaptation of muscle to aerobic training associates not only with the transitory changes in gene expression after each exercise, but also with the marked changes in transcriptome in basal state. This work was supported by the Russian Science Foundation (14­15­00768).

scholarly journals REDD1 induction regulates the skeletal muscle gene expression signature following acute aerobic exercise

2017 ◽  
Vol 313 (6) ◽  
pp. E737-E747 ◽  
Author(s):  
Bradley S. Gordon ◽  
Jennifer L. Steiner ◽  
Michael L. Rossetti ◽  
Shuxi Qiao ◽  
Leif W. Ellisen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Aerobic Exercise ◽  
Acute Exercise ◽  
Gene Expression Signature ◽  
Model Systems ◽  
Expression Signature ◽  
Altered Gene Expression ◽  
Altered Gene ◽  
Exercise Induced

The metabolic stress placed on skeletal muscle by aerobic exercise promotes acute and long-term health benefits in part through changes in gene expression. However, the transducers that mediate altered gene expression signatures have not been completely elucidated. Regulated in development and DNA damage 1 (REDD1) is a stress-induced protein whose expression is transiently increased in skeletal muscle following acute aerobic exercise. However, the role of this induction remains unclear. Because REDD1 altered gene expression in other model systems, we sought to determine whether REDD1 induction following acute exercise altered the gene expression signature in muscle. To do this, wild-type and REDD1-null mice were randomized to remain sedentary or undergo a bout of acute treadmill exercise. Exercised mice recovered for 1, 3, or 6 h before euthanization. Acute exercise induced a transient increase in REDD1 protein expression within the plantaris only at 1 h postexercise, and the induction occurred in both cytosolic and nuclear fractions. At this time point, global changes in gene expression were surveyed using microarray. REDD1 induction was required for the exercise-induced change in expression of 24 genes. Validation by RT-PCR confirmed that the exercise-mediated changes in genes related to exercise capacity, muscle protein metabolism, neuromuscular junction remodeling, and Metformin action were negated in REDD1-null mice. Finally, the exercise-mediated induction of REDD1 was partially dependent upon glucocorticoid receptor activation. In all, these data show that REDD1 induction regulates the exercise-mediated change in a distinct set of genes within skeletal muscle.

Thyroid hormones and the mRNA of the GH receptor and IGFs in skeletal muscle of fetal sheep

2002 ◽  
Vol 282 (1) ◽  
pp. E80-E86 ◽  
Author(s):  
A. J. Forhead ◽  
J. Li ◽  
R. S. Gilmour ◽  
M. J. Dauncey ◽  
A. L. Fowden
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Thyroid Hormones ◽  
Gestational Age ◽  
Plasma Cortisol ◽  
Mrna Abundance ◽  
Late Gestation ◽  
Fetal Sheep ◽  
Igf I ◽  
I Gene

Thyroid hormones are required for the normal development of skeletal muscle in utero, although their mechanism of action is poorly understood. The present study examined the effects of the thyroid hormones on the gene expression of the growth hormone receptor (GHR) and the insulin-like growth factors (IGFs) IGF-I and IGF-II, in skeletal muscle of fetal sheep during late gestation (term 145 ± 2 days) and after manipulation of plasma thyroid hormone concentration. Thyroidectomy at 105–110 days of gestation suppressed muscle GHR and IGF-I gene expression in fetuses studied at 127–130 and 142–145 days. Muscle GHR mRNA abundance remained unchanged with increasing gestational age in intact and thyroidectomized fetuses. In the intact fetuses, a decrease in muscle IGF-I gene expression was observed between 127–130 and 142–145 days, which coincided with the normal prepartum surges in plasma cortisol and triiodothyronine (T3). At 127–130 days, downregulation of muscle IGF-I mRNA abundance was induced prematurely in intact fetuses by an infusion of cortisol for 5 days (2–3 mg · kg−1 · day−1 iv), which increased plasma cortisol and T3 concentrations to values seen near term. However, increasing plasma T3 alone by an infusion of T3 for 5 days (8–12 μg · kg−1 · day−1 iv) in intact fetuses at this age had no effect on GHR or IGF-I gene expression in skeletal muscle. In the thyroidectomized fetuses, no additional change in the low level of muscle IGF-I mRNA abundance was seen with increasing gestational age, but at 127–130 days, IGF-I gene expression was reduced further when plasma cortisol and T3 concentrations were increased by exogenous cortisol infusion. Muscle IGF-II mRNA abundance was not affected by thyroidectomy, gestational age, or exogenous hormone infusion. These findings show, in the sheep fetus, that thyroid hormones may influence the growth and development of skeletal muscle via changes in the local activity of the somatotrophic axis.

scholarly journals Integrating the analysis of transcriptome-wide association study and gene expression profile to identify genes associated with spondyloarthritis

2021 ◽  
Author(s):  
Jiawen Xu ◽  
Haibo Si ◽  
Yi Zeng ◽  
Yuangang Wu ◽  
Shaoyun Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Association Study ◽  
Candidate Genes ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Whole Blood ◽  
Genome Wide Association Study ◽  
Bone Diseases ◽  
Functional Enrichment

Abstract Background Spondyloarthritis(SpA) is a group of multi-factorial bone diseases influenced by genetic factors, environment and lifestyles. However, the genetic and pathogenic mechanism of SpA is still elusive. Methods Firstly, the tissue-specific transcriptome-wide association study (TWAS) of SpA was performed by utilizing the genome-wide association study (GWAS, including 3966 SpA patients and 452264 controls) summary data and gene expression weights of the whole blood and skeletal muscle. Secondly, the SpA-associated genes identified by TWAS were further compared with the differentially expressed genes(DEGs) detected by gene expression profile of SpA acquired from the Gene Expression Omnibus database (GEO, accession number:GSE58667). Finally, FUMA and Metascape tools were used to conduct gene functional enrichment and annotation analysis. Results TWAS detected 28 significant genes associated with SpA both in the whole blood and skeletal muscle, such as CTNNAL1 (PSM=0.0304, PWB=0.0096). Further comparing with gene expression profile of SpA, we identified 20 candidate genes which overlapped in TWAS, such as MCM4 (PTWAS=0.0132, PDEG=0.0275), KIAA1109 (PTWAS=0.0371,PDEG=0.0467). The enrichment analysis of the genes identified by TWAS detected 93 significant GO terms 33 and KEGG pathways, such as mitochondrion organization (GO:0007005, log10(P)= -4.29) and axon guidance(hsa04360, log10(P)= -4.26). Conclusion We identified multiple candidate genes genetically related to SpA. Our study may provide some novel clues for the further study of the genetic mechanism, diagnosis and treatment of SpA.

scholarly journals Post‐exercise feeding attenuates proteolytic gene expression in human skeletal muscle

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Matthew Harber ◽  
Adam Konopka ◽  
Bozena Jemiolo ◽  
Todd Trappe ◽  
Scott Trappe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Post Exercise

scholarly journals Selection-, age-, and exercise-dependence of skeletal muscle gene expression patterns in a rat model of metabolic fitness

2016 ◽  
Vol 48 (11) ◽  
pp. 816-825 ◽  
Author(s):  
Yu-yu Ren ◽  
Lauren G. Koch ◽  
Steven L. Britton ◽  
Nathan R. Qi ◽  
Mary K. Treutelaar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Complex Traits ◽  
Cellular Response ◽  
Acute Exercise ◽  
Expression Patterns ◽  
Age Groups ◽  
Health Indicators ◽  
Strenuous Exercise ◽  
Endurance Running

Intrinsic aerobic exercise capacity can influence many complex traits including obesity and aging. To study this connection we established two rat lines by divergent selection of untrained aerobic capacity. After 32 generations the high capacity runners (HCR) and low capacity runners (LCR) differed in endurance running distance and body fat, blood glucose, other health indicators, and natural life span. To understand the interplay among genetic differences, chronological age, and acute exercise we performed microarray-based gene expression analyses in skeletal muscle with a 2×2×2 design to simultaneously compare HCR and LCR, old and young animals, and rest and exhaustion. Transcripts for mitochondrial function are expressed higher in HCRs than LCRs at both rest and exhaustion and for both age groups. Expression of cell adhesion and extracellular matrix genes tend to decrease with age. This and other age effects are more prominent in LCRs than HCRs, suggesting that HCRs have a slower aging process and this may be partly due to their better metabolic health. Strenuous exercise mainly affects transcription regulation and cellular response. The effects of any one factor often depend on the other two. For example, there are ∼140 and ∼110 line-exercise “interacting” genes for old and young animals, respectively. Many genes highlighted in our study are consistent with prior reports, but many others are novel. The gene- and pathway-level statistics for the main effects, either overall or stratified, and for all possible interactions, represent a rich reference dataset for understanding the interdependence among lines, aging, and exercise.

Sign in / Sign up

Export Citation Format

Share Document