Electrical pulse stimulation of cultured skeletal muscle cells as a model for <i>in vitro</i> exercise – possibilities and limitations

Nikolić, Nataša; Görgens, Sven W.; Thoresen, G. Hege; Aas, Vigdis; Eckel, Jürgen; Eckardt, Kristin

doi:10.1111/apha.12830

Cited by 90 publications

(133 citation statements)

References 163 publications

(190 reference statements)

Supporting

Mentioning

130

Contrasting

Order By: Relevance

“…This might be caused by technical limitations, such as electric pulse stimulation mimicking only part of the exercise responses (Nikolic et al, 2017). To address this question, we established an in vitro exercise model by applying electric pulse stimulation to C2C12 myotubes.…”

Section: Discussionmentioning

confidence: 99%

Skeletal muscle‐derived exosomes regulate endothelial cell functions via reactive oxygen species‐activated nuclear factor‐κB signalling

Nie

Sato

Garner

et al. 2019

Experimental Physiology

View full text Add to dashboard Cite

New Findings What is the central question of this study?Capillary rarefaction is found in diabetic and aged muscle, whereas exercise increases skeletal muscle angiogenesis. The association implies a crosstalk between muscle cells and endothelial cells. The underlying mechanisms mediating the crosstalk between these cells remains to be elucidated fully. What is the main finding and its importance?Endothelial cell functions are regulated by skeletal muscle cell‐derived exosomes via a vascular endothelial growth factor‐independent pathway. This study reveals a new mechanism mediating the crosstalk between skeletal muscle cells and endothelial cells. Abstract Loss of skeletal muscle capillarization, known as capillary rarefaction, is found in type 2 diabetes, chronic heart failure and healthy ageing and is associated with impaired delivery of substrates to the muscle. However, the interaction and communication of skeletal muscle with endothelial cells in the regulation of capillaries surrounding the muscle remains elusive. Exosomes are a type of secreted extracellular vesicle containing mRNAs, proteins and, especially, microRNAs that exert paracrine and endocrine effects. In this study, we investigated whether skeletal muscle‐derived exosomes (SkM‐Exo) regulate the endothelial cell functions of angiogenesis. We demonstrated that C2C12 myotube‐derived exosomes improved endothelial cell functions, assessed by the proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs), which were increased by 20, 23 and 40%, respectively, after SkM‐Exo exposure. The SkM‐Exo failed to activate HUVEC vascular endothelial growth factor (VEGF) signalling. The SkM‐Exo increased HUVEC reactive oxygen species and activated the nuclear factor‐κB pathway, suggesting that SkM‐Exo‐induced angiogenesis was mediated by a VEGF‐independent pathway. In addition, several angiogenic microRNAs were packaged in SkM‐Exo, with miR‐130a being particularly enriched and successfully transferred from SkM‐Exo to HUVECs. Delivery of miRNAs into endothelial cells might explain the enhancement of reactive oxygen species production and angiogenesis by SkM‐Exo. The potential angiogenic effect of SkM‐Exo could provide an effective therapy for promoting skeletal muscle angiogenesis in diseases characterized by capillary rarefaction or inadequate angiogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Skeletal muscle‐derived exosomes regulate endothelial cell functions via reactive oxygen species‐activated nuclear factor‐κB signalling

Nie

Sato

Garner

et al. 2019

Experimental Physiology

View full text Add to dashboard Cite

show abstract

“…; Nikolić et al . ), reduced ATP and phosphocreatine concentations (Nedachi et al . ; Nikolić et al .…”

Section: Introductionmentioning

confidence: 99%

Electrical pulse stimulation: an in vitro exercise model for the induction of human skeletal muscle cell hypertrophy. A proof‐of‐concept study

Tarum

Folkesson

Atherton

et al. 2017

Experimental Physiology

View full text Add to dashboard Cite

What is the central question of this study? Is electrical pulse stimulation (EPS) an in vitro exercise model able to elicit the hypertrophy of human muscle cells? What is the main finding and its importance? The addition of a restitution period of 8 h after EPS induces the enlargement of human muscle cells, a major physiological end-point to resistance exercise. This is supported by downregulation of myostatin, a negative regulator of muscle mass, and increased phosphorylated mTOR and 4E-BP1, key factors in the growth cascade. This proof-of-concept study provides a model of physiologically mediated muscle growth, which will be the basis for future studies aiming to depict molecular events governing the hypertrophy of human muscle cells. Electrical pulse stimulation (EPS) of muscle cells has previously been used as an in vitro exercise model. The present study aimed to establish an EPS protocol promoting the hypertrophy of human muscle cells, which represents a major physiological end-point to resistance exercise in humans. We hypothesized that adding a resting period after EPS would be crucial for the occurrence of the morphological change. Myoblasts obtained from human muscle biopsies (n = 5) were differentiated into multinucleated myotubes and exposed to 8 h of EPS consisting of 2 ms pulses at 12 V, with a frequency of 1 Hz. Myotube size was assessed using immunohistochemistry immediately, 4 and 8 h after completed EPS. Gene expression and phosphorylation status of selected markers of hypertrophy were assessed using RT-PCR and Western blotting, respectively. Release of the myokine interleukin-6 in culture medium was measured using enzyme-linked immunosorbent assay. We demonstrated a significant increase (31 ± 14%; P = 0.03) in the size of myotubes when EPS was followed by an 8 h resting period, but not immediately or 4 h after completion of EPS. The response was supported by downregulation (P = 0.04) of the gene expression of myostatin, a negative regulator of muscle mass, and an increase in phosphorylated mTOR (P = 0.03) and 4E-BP1 (P = 0.01), which are important factors in the cellular growth signalling cascade. The present work demonstrates that EPS is an in vitro exercise model promoting the hypertrophy of human muscle cells, recapitulating a major physiological end-point to resistance exercise in human skeletal muscle.

show abstract

“…This results in a reduction of muscle mass and increased obesity and often in the development of chronic diseases . Exercise improves whole‐body glucose tolerance and increases the insulin sensitivity . At the molecular level, muscle contraction activates the transport of glucose.…”

mentioning

confidence: 99%

“…This results in a decrease in the insulin concentration needed to induce 50% of the maximum response . Regular physical activity reduces the risk of several chronic diseases, for example type 2 diabetes, cardiovascular diseases, dementia, depression and several types of cancer . Both, young and old subjects benefit from endurance training, for example increased insulin sensitivity.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Skeletal muscle in the fight against chronic diseases

Mrowka

Westphal

2018

Acta Physiologica

View full text Add to dashboard Cite

Electrical pulse stimulation of cultured skeletal muscle cells as a model for in vitro exercise – possibilities and limitations

Cited by 90 publications

References 163 publications

Skeletal muscle‐derived exosomes regulate endothelial cell functions via reactive oxygen species‐activated nuclear factor‐κB signalling

Skeletal muscle‐derived exosomes regulate endothelial cell functions via reactive oxygen species‐activated nuclear factor‐κB signalling

Electrical pulse stimulation: an in vitro exercise model for the induction of human skeletal muscle cell hypertrophy. A proof‐of‐concept study

Skeletal muscle in the fight against chronic diseases

Contact Info

Product

Resources

About