The role of IGF-1 signaling in skeletal muscle atrophy
| Autor: | Richard T. Jaspers, Louk T. Timmer, Willem M.H. Hoogaars |
|---|---|
| Přispěvatelé: | Physiology, AMS - Restoration and Development, AMS - Ageing and Morbidity, AMS - Fundamental Research |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Denervation Aging Chemistry Calpain Growth factor medicine.medical_treatment Protein turnover Hypertrophy Protein degradation Caspase Lysosome Muscle atrophy Muscle hypertrophy Cell biology 03 medical and health sciences 030104 developmental biology medicine medicine.symptom Disuse Protein kinase B PI3K/AKT/mTOR pathway miRNA |
| Zdroj: | Muscle atrophy, 1088, 109-137 Advances in Experimental Medicine and Biology ISBN: 9789811314346 Timmer, L T, Hoogaars, W M H & Jaspers, R T 2018, The role of IGF-1 signaling in skeletal muscle atrophy . in Muscle atrophy . vol. 1088, Advances in Experimental Medicine and Biology, vol. 1088, Springer New York LLC, pp. 109-137 . https://doi.org/10.1007/978-981-13-1435-3_6 |
| ISSN: | 0065-2598 |
| Popis: | Insulin-like growth factor 1 (IGF-1) is a key anabolic growth factor stimulating phosphatidylinositol 3-kinase (PI3K)/Akt signaling which is well known for regulating muscle hypertrophy. However, the role of IGF-1 in muscle atrophy is less clear. This review provides an overview of the mechanisms via which IGF-1 signaling is implicated in several conditions of muscle atrophy and via which mechanisms protein turnover is altered. IGF-1/PI3K/Akt signaling stimulates the rate of protein synthesis via p70S6Kinase and p90 ribosomal S6 kinase and negatively regulates protein degradation, predominantly by its inhibiting effect on proteasomal and lysosomal protein degradation. Caspase-dependent protein degradation is also attenuated by IGF/PI3K/Akt signaling, whereas evidence for an effect on calpain-dependent protein degradation is inconclusive. IGF-1/PI3K/Akt signaling reduces during denervation-, unloading-, and joint immobilization-induced muscle atrophy, whereas IGF-1/PI3K/Akt signaling seems unaltered during aging-associated muscle atrophy. During denervation and aging, IGF-1 overexpression or injection counteracts denervation- and aging-associated muscle atrophy, despite enhanced anabolic resistance with regard to IGF-1 signaling with aging. It remains unclear whether pharmacological stimulation of IGF-1/PI3K/Akt signaling attenuates immobilization- or unloading-induced muscle atrophy. Exploration of the possibilities to interfere with IGF-1/PI3K/Akt signaling reveals that microRNAs targeting IGF-1 signaling components are promising targets to counterbalance muscle atrophy. Overall, the findings summarized in this review show that in disuse conditions, but not with aging, IGF-1/PI3K/Akt signaling is attenuated and that in some conditions stimulation of this pathway may alleviate skeletal muscle atrophy. |
| Databáze: | OpenAIRE |
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