Deficient nitric oxide signalling impairs skeletal muscle growth and performance: involvement of mitochondrial dysregulation.

Background: Nitric oxide (NO), generated in skeletal muscle mostly by the neuronal NO synthases (nNOSμ), has profound effects on both mitochondrial bioenergetics and muscle development and function. The importance of NO for muscle repair emerges from the observation that nNOS signalling is defective in many genetically diverse skeletal muscle diseases in which muscle repair is dysregulated. How the effects of NO/nNOSμ on mitochondria impact on muscle function, however, has not been investigated yet.

Autophagy is not required to sustain exercise and PRKAA1/AMPK activity but is important to prevent mitochondrial damage during physical activity.

Physical activity has been recently documented to play a fundamental physiological role in the regulation of autophagy in several tissues. It has also been reported that autophagy is required for exercise itself and for training-induced adaptations in glucose homeostasis. These autophagy-mediated metabolic improvements are thought to be largely dependent on the activation of the metabolic sensor PRKAA1/AMPK.

Autophagy impairment in muscle induces neuromuscular junction degeneration and precocious aging.

The cellular basis of age-related tissue deterioration remains largely obscure. The ability to activate compensatory mechanisms in response to environmental stress is an important factor for survival and maintenance of cellular functions. Autophagy is activated both under short and prolonged stress and is required to clear the cell of dysfunctional organelles and altered proteins.

Role of autophagy, SQSTM1, SH3GLB1, and TRIM63 in the turnover of nicotinic acetylcholine receptors.

Removal of ubiquitinated targets by autophagosomes can be mediated by receptor molecules, like SQSTM1, in a mechanism referred to as selective autophagy. While cytoplasmic protein aggregates, mitochondria, and bacteria are the best-known targets of selective autophagy, their role in the turnover of membrane receptors is scarce. We here showed that fasting-induced wasting of skeletal muscle involves remodeling of the neuromuscular junction (NMJ) by increasing the turnover of muscle-type CHRN (cholinergic receptor, nicotinic/nicotinic acetylcholine receptor) in a TRIM63-dependent manner.

Intracellular signaling in ER stress-induced autophagy in skeletal muscle cells.

Skeletal muscle remodeling in response to muscle disuse and unloading is known to be associated with so-called ER stress, which, in turn, activates autophagy and contributes to muscle atrophy. Different molecules are involved in ER stress-induced autophagy, among which PKCθ has recently been described. In this study, we dissected both in vitro and in vivo ER stress-induced autophagy pathways in muscle.

JunB transcription factor maintains skeletal muscle mass and promotes hypertrophy.

The size of skeletal muscle cells is precisely regulated by intracellular signaling networks that determine the balance between overall rates of protein synthesis and degradation. Myofiber growth and protein synthesis are stimulated by the IGF-1/Akt/mammalian target of rapamycin (mTOR) pathway. In this study, we show that the transcription factor JunB is also a major determinant of whether adult muscles grow or atrophy.

Three-dimensional porous scaffold allows long-term wild-type cell delivery in dystrophic muscle.

Duchenne muscular dystrophy (DMD) is caused by the lack of dystrophin; affected muscles are characterized by continuous bouts of muscle degeneration, eventually leading to the exhaustion of the endogenous satellite cell pool. At present, only palliative treatments are available, although several gene and cell therapy-based approaches are being studied. In this study we proposed to overcome the limitations hampering intramuscular cell injection by using a biomaterial-based strategy.

Electrophysiologic stimulation improves myogenic potential of muscle precursor cells grown in a 3D collagen scaffold.

The production of engineered three-dimensional (3D) skeletal muscle grafts holds promise for treatment of several diseases. An important factor in the development of such approach involves the capability of preserving myogenicity and regenerative potential during ex vivo culturing. We have previously shown that electrical stimulation of myogenic cells grown in monolayer could improve the differentiation process.