Age-associated changes in MAPK activation in fast- and slow-twitch skeletal muscle of the F344/NNiaHSD X Brown Norway/BiNia rat model

Mylabathula, Deepak B.; Rice, Kevin M.; Wang, Z.; Uddemarri, S.; Kinnard, Randy S.; Blough, Eric R.

doi:10.1016/j.exger.2005.11.001

Cited by 31 publications

(30 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, total AMPK and p38 contents were higher in muscle from mdx mice compared with WT animals. Multiple muscle pathologies, including muscular dystrophy (4, 60) and aging-associated sarcopenia (38,51,68), display an elevation in total kinase content. A greater basal kinase enzyme concentration in dystrophic muscle may represent a compensatory adaptation in an attempt to attain the necessary signaling apparatus to be responsive to local cues, including phenotype-shifting stimuli such as mechanical stress, and intracellular calcium or highenergy phosphate flux.…”

Section: Discussionmentioning

confidence: 99%

Chronic AMPK stimulation attenuates adaptive signaling in dystrophic skeletal muscle

Ljubicic

Khogali

Renaud

et al. 2012

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

In the present study, we evaluated how a pharmacologically induced phenotype shift in dystrophic skeletal muscle would affect subsequent intracellular signaling in response to a complementary, adaptive physiological stimulus. mdx mice were treated with the AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR; 500 mg·kg(-1)·day(-1)) for 30 days, and then one-half of the animals were subjected to a bout of treadmill running to induce acute AMPK and p38 MAPK signaling. The mRNA levels of phenotypic modifiers, including peroxisome proliferator-activated receptor-δ (PPARδ), PPARγ coactivator-1α (PGC-1α), receptor interacting protein 140 (RIP 140), and silent information regulator two ortholog 1 (SIRT1) were assessed in skeletal muscle, as well as the expression of the protein arginine methyltransferase genes PRMT1 and CARM1. We found unique AMPK and p38 phosphorylation and expression signatures between dystrophic and healthy muscle. In dystrophic skeletal muscle, treadmill running induced PPARδ, PGC-1α, and SIRT1 mRNAs, three molecules that promote the slow, oxidative myogenic program. In the mdx animals that received the chronic AICAR treatment, running-elicited AMPK and p38 phosphorylation was attenuated compared with vehicle-treated mice. Similarly, acute stress-evoked expression of PPARδ, PGC-1α, and SIRT1 was also blunted by chronic pharmacological AMPK stimulation. Skeletal muscle PRMT1 and CARM1 protein contents were higher in mdx mice compared with wild-type littermates. The acute running-evoked induction of PRMT1 and CARM1 mRNAs was also attenuated by the AICAR treatment. Our data demonstrate that prior pharmacological conditioning is a salient determinant in how dystrophic muscle adapts to subsequent complementary, acute physiological stress stimuli. These results provide insight into possible therapeutic applications of synthetic agonists in neuromuscular diseases, such as during chronic administration to Duchenne muscular dystrophy patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Chronic AMPK stimulation attenuates adaptive signaling in dystrophic skeletal muscle

Ljubicic

Khogali

Renaud

et al. 2012

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

show abstract

“…Muscle dysfunction, linked to SMA, could account for the elevated AMPK activity found in our model. According to this possibility, increases in the expression and activity of different kinases have been observed in a variety of muscle pathologies [62,[90][91][92].…”

Section: Discussionmentioning

confidence: 99%

Chronic Treatment with the AMPK Agonist AICAR Prevents Skeletal Muscle Pathology but Fails to Improve Clinical Outcome in a Mouse Model of Severe Spinal Muscular Atrophy

et al. 2016

View full text Add to dashboard Cite

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder characterized by spinal and brainstem motor neuron (MN) loss and skeletal muscle paralysis. Currently, there is no effective treatment other than supportive care to ameliorate the quality of life of patients with SMA. Some studies have reported that physical exercise, by improving muscle strength and motor function, is potentially beneficial in SMA. The adenosine monophosphate-activated protein kinase agonist 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) has been reported to be an exercise mimetic agent that is able to regulate muscle metabolism and increase endurance both at rest and during exercise. Chronic AICAR administration has been shown to ameliorate the dystrophic muscle phenotype and motor behavior in the mdx mouse, a model of Duchenne muscular dystrophy. Here, we investigated whether chronic AICAR treatment was able to elicit beneficial effects on motor abilities and neuromuscular histopathology in a mouse model of severe SMA (the SMNΔ7 mouse). We report that AICAR improved skeletal muscle atrophy and structural changes found in neuromuscular junctions of SMNΔ7 animals. However, although AICAR prevented the loss of glutamatergic excitatory synapses on MNs, this compound was not able to mitigate MN loss or the microglial and astroglial reaction occurring in the spinal cord of diseased mice. Moreover, no improvement in survival or motor performance was seen in SMNΔ7 animals treated with AICAR. The beneficial effects of AICAR in SMA found in our study are SMN-independent, as no changes in the expression of this protein were seen in the spinal cord and skeletal muscle of diseased animals treated with this compound.

show abstract

“…Furthermore it has been shown that stretch direction affects signalling intensity, with transverse stretching of the diaphragm leading to higher activity of the p38, JNK, and ERK pathways compared to axial strain in the direction of the myofibres 103 . Interestingly, aged skeletal muscle responds differently to stretch-induced MAPK activity, depending on the type of myofibre (fast or slow twitching) 105 .…”

Section: Mechanical Loads -Stretch and Shear Forcesmentioning

confidence: 99%

Biomechanical Origins of Muscle Stem Cell Signal Transduction

Morrissey

Cheng

Davoudi

et al. 2016

Journal of Molecular Biology

View full text Add to dashboard Cite

Age-associated changes in MAPK activation in fast- and slow-twitch skeletal muscle of the F344/NNiaHSD X Brown Norway/BiNia rat model

Cited by 31 publications

References 45 publications

Chronic AMPK stimulation attenuates adaptive signaling in dystrophic skeletal muscle

Chronic AMPK stimulation attenuates adaptive signaling in dystrophic skeletal muscle

Chronic Treatment with the AMPK Agonist AICAR Prevents Skeletal Muscle Pathology but Fails to Improve Clinical Outcome in a Mouse Model of Severe Spinal Muscular Atrophy

Biomechanical Origins of Muscle Stem Cell Signal Transduction

Contact Info

Product

Resources

About