Trichostatin A, a histone deacetylase inhibitor, modulates unloaded-induced skeletal muscle atrophy.

Skeletal muscle atrophy is commonly associated with immobilization, ageing, and catabolic diseases such as diabetes and cancer cachexia. Epigenetic regulation of gene expression resulting from chromatin remodeling through histone acetylation has been implicated in muscle disuse. The present work was designed to test the hypothesis that treatment with trichostatin A (TSA), a histone deacetylase inhibitor, would partly counteract unloading-induced muscle atrophy.

Hypoxia refines plasticity of mitochondrial respiration to repeated muscle work.

Purpose: We explored whether altered expression of factors tuning mitochondrial metabolism contributes to muscular adaptations with endurance training in the condition of lowered ambient oxygen concentration (hypoxia) and whether these adaptations relate to oxygen transfer as reflected by subsarcolemmal mitochondria and oxygen metabolism in muscle.

Methods: Male volunteers completed 30 bicycle exercise sessions in normoxia or normobaric hypoxia (4,000 m above sea level) at 65% of the respective peak aerobic power output. Myoglobin content, basal oxygen consumption, and re-oxygenation rates upon reperfusion after 8 min of arterial occlusion were measured in vastus muscles by magnetic resonance spectroscopy.

Oxidative stress, apoptosis, and proteolysis in skeletal muscle repair after unloading.

Although several lines of evidence link muscle-derived oxidants and inflammation to skeletal muscle wasting via regulation of apoptosis and proteolysis, little information is currently available on muscle repair. The present work was designed to study oxidative stress response, inflammatory cytokines, apoptotic, or proteolytic pathways during the early (1 and 5 days) and later (14 days) stages of the regrowth process subsequent to 14 days of hindlimb unloading. During the early stages of reloading, muscle mass recovery (day 5) was facilitated by transcriptional downregulation (day 1) of pathways involved in muscle proteolysis [mu-calpain, atrogin-1/muscle atrophy F-box (MAFbx), and muscle RING finger-1/(MuRF1) mRNA] and upregulation of an autophagy-related protein Beclin-1 (day 5).

Altered myoplasmic Ca(2+) handling in rat fast-twitch skeletal muscle fibres during disuse atrophy.

Calcium-dependent signalling pathways are believed to play an important role in skeletal muscle atrophy, but whether intracellular Ca(2+) homeostasis is affected in that situation remains obscure. We show here that there is a 20% atrophy of the fast-type flexor digitorum brevis (FDB) muscle in rats hind limb unloaded (HU) for 2 weeks, with no change in fibre type distribution. In voltage-clamp experiments, the amplitude of the slow Ca(2+) current was found similar in fibres from control and HU animals.

ACTH-induced Cl(-) current in bovine adrenocortical cells: correlation with cortisol secretion.

ACTH has been shown to depolarize bovine adrenal zona fasciculata cells by inhibiting a K(+) current. The effects of this hormone on such cells have been reexamined using perforated and standard patch recording methods. In current clamp experiments, ACTH (10 nM) induced a membrane depolarization to -36 +/- 1 mV (n = 56), which was mimicked by forskolin (10 microM) or by 8-(4-chlorophenylthio)-cAMP (8 mM).