Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Regulators of skeletal muscle mass are of interest, given the morbidity and mortality of muscle atrophy and myopathy. Four-and-a-half LIM protein 1 (FHL1) is mutated in several human myopathies, including reducing-body myopathy (RBM). The normal function of FHL1 in muscle and how it causes myopathy remains unknown. We find that FHL1 transgenic expression in mouse skeletal muscle promotes hypertrophy and an oxidative fiber-type switch, leading to increased whole-body strength and fatigue resistance. Additionally, FHL1 overexpression enhances myoblast fusion, resulting in hypertrophic myotubes in C2C12 cells, (a phenotype rescued by calcineurin inhibition). In FHL1-RBM C2C12 cells, there are no hypertrophic myotubes. FHL1 binds with the calcineurin-regulated transcription factor NFATc1 (nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 1), enhancing NFATc1 transcriptional activity. Mutant RBM-FHL1 forms aggregate bodies in C2C12 cells, sequestering NFATc1 and resulting in reduced NFAT nuclear translocation and transcriptional activity. NFATc1 also colocalizes with mutant FHL1 to reducing bodies in RBM-afflicted skeletal muscle. Therefore, via NFATc1 signaling regulation, FHL1 appears to modulate muscle mass and strength enhancement.
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PMID:Identification of FHL1 as a regulator of skeletal muscle mass: implications for human myopathy. 1907 12

During their annual breeding migration the Christmas Island land crab Gecarcoidea natalis sustains locomotion aerobically for up to 12 h per day compared with just 10 min during the dry season when their muscles quickly become anaerobic. A seasonal transition to an endurance-muscle phenotype would thus seem essential for migrating crabs. The current study employed a gene discovery approach comparing two expressed sequence tag (EST) libraries, one each for leg muscle from dry (non-migrating) and wet season (migrating) crabs. The 14 most abundant transcripts differed in their representation between the two libraries. The abundances of transcripts of genes predicted to code for different proteins forming contractile muscle components, including actin, troponin and tropomyosin, were significantly different between seasons and thus between physiological states. The shift in the isoform composition of the contractile elements provided evidence for a switch from slow phasic (S1) to slow tonic (S2) fatigue-resistant muscle fibres. A tropomyosin (tm) transcript aligned with a tm isoform of lobster (tmS2), and semi-quantitative RT-PCR confirmed this isoform to be more abundant in the migrating crab muscle. Two LIM protein coding genes, a paxillin-like transcript (pax) and a muscle LIM protein (mlp), were relatively up-regulated in muscle of wet season crabs. These proteins have a fundamental role in muscle development and reconstruction, and their comparative up-regulation is consistent with a remodelling of leg muscle for migration in the wet season. Such a transition would result in an increased representation of aerobic endurance-type fibres concomitant with the greater aerobic exercise capacity of the migrating red crabs.
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PMID:Migration-related changes in gene expression in leg muscle of the Christmas Island red crab Gecarcoidea natalis: seasonal preparation for long-distance walking. 2043 25