Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Skeletal muscle atrophy is a debilitating response to starvation and many systemic diseases including diabetes, cancer, and renal failure. We had proposed that a common set of transcriptional adaptations underlie the loss of muscle mass in these different states. To test this hypothesis, we used cDNA microarrays to compare the changes in content of specific mRNAs in muscles atrophying from different causes. We compared muscles from fasted mice, from rats with cancer cachexia, streptozotocin-induced diabetes mellitus, uremia induced by subtotal nephrectomy, and from pair-fed control rats. Although the content of >90% of mRNAs did not change, including those for the myofibrillar apparatus, we found a common set of genes (termed atrogins) that were induced or suppressed in muscles in these four catabolic states. Among the strongly induced genes were many involved in protein degradation, including polyubiquitins, Ub fusion proteins, the Ub ligases atrogin-1/MAFbx and MuRF-1, multiple but not all subunits of the 20S proteasome and its 19S regulator, and cathepsin L. Many genes required for ATP production and late steps in glycolysis were down-regulated, as were many transcripts for extracellular matrix proteins. Some genes not previously implicated in muscle atrophy were dramatically up-regulated (lipin, metallothionein, AMP deaminase, RNA helicase-related protein, TG interacting factor) and several growth-related mRNAs were down-regulated (P311, JUN, IGF-1-BP5). Thus, different types of muscle atrophy share a common transcriptional program that is activated in many systemic diseases.
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PMID:Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression. 1471 85

Muscle growth is determined primarily by the balance between protein synthesis and degradation. When rates of protein synthesis are similar between individuals, protein degradation is critical in explaining differences in growth efficiency. Studies in mammals showed that muscle atrophy results from increased protein breakdown, and is associated with activation of the ubiquitin proteasome pathway, including induction of the muscle-specific ubiquitin protein ligase, MuRF1. Animals lacking MuRF1 are resistant to muscle atrophy. In fish, little is known about the role of the proteasome/MuRF pathway in muscle degradation. The objectives of this study were to: 1) clone and characterize MuRF genes in rainbow trout; and 2) determine expression of MuRF genes in association with starvation- and vitellogenesis-induced muscle atrophy in rainbow trout. We have identified full-length cDNA sequences for three MuRF genes (MuRF1, MuRF2, and MuRF3). These genes encode proteins with typical MuRF structural domains, including a RING-finger, a B-box and a Leucine-rich coiled-coil domain. RT-PCR analysis showed that MuRF genes are predominantly expressed in muscle and heart tissues. Real time PCR analysis revealed that expression of all MuRF genes is up-regulated during starvation and MuRF3 is up-regulated in vitellogenesis-associated muscle degradation. These results suggest that MuRF genes have an important role in fish muscle protein degradation. Further studies are warranted to assess the potential use of MuRF genes as tools to monitor fish muscle growth and degradation.
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PMID:Molecular characterization of the MuRF genes in rainbow trout: Potential role in muscle degradation. 2114 12

Many pathological states characterized by muscle atrophy (e.g., sepsis, cachexia, starvation, metabolic acidosis and severe insulinopenia) are associated with an increase in circulating glucocorticoids (GC) levels, suggesting that GC could trigger the muscle atrophy observed in these conditions. GC-induced muscle atrophy is characterized by fast-twitch, glycolytic muscles atrophy illustrated by decreased fiber cross-sectional area and reduced myofibrillar protein content. GC-induced muscle atrophy results from increased protein breakdown and decreased protein synthesis. Increased muscle proteolysis, in particular through the activation of the ubiquitin proteasome and the lysosomal systems, is considered to play a major role in the catabolic action of GC. The stimulation by GC of these two proteolytic systems is mediated through the increased expression of several Atrogenes ("genes involved in atrophy"), such as FOXO, Atrogin-1, and MuRF-1. The inhibitory effect of GC on muscle protein synthesis is thought to result mainly from the inhibition of the mTOR/S6 kinase 1 pathway. These changes in muscle protein turnover could be explained by changes in the muscle production of two growth factors, namely Insulin-like Growth Factor (IGF)-I, a muscle anabolic growth factor and Myostatin, a muscle catabolic growth factor. This review will discuss the recent progress made in the understanding of the mechanisms involved in GC-induced muscle atrophy and consider the implications of these advancements in the development of new therapeutic approaches for treating GC-induced myopathy. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting.
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PMID:Glucocorticoid-induced skeletal muscle atrophy. 2380 68

Skeletal muscle atrophy is often caused by catabolic conditions including fasting, disuse, aging and chronic diseases, such as chronic obstructive pulmonary disease. Atrophy occurs when the protein degradation rate exceeds the rate of protein synthesis. Therefore, maintaining a balance between the synthesis and degradation of protein in muscle cells is a major way to prevent skeletal muscle atrophy. Ginsenoside Rg1 (Rg1) is a primary active ingredient in Panax ginseng, which is considered to be one of the most valuable herbs in traditional Chinese medicine. In the current study, Rg1 was observed to inhibit the expression of MuRF-1 and atrogin-1 in C2C12 muscle cells in a starvation model. Rg1 also activated the phosphorylation of mammalian target of rapamycin (mTOR), protein kinase B (AKT), and forkhead transcription factor O, subtypes 1 and 3a. This phosphorylation was inhibited by LY294002, a phosphatidylinositol 3-kinase inhibitor. These data suggest that Rg1 may participate in the regulation of the balance between protein synthesis and degradation, and that the function of Rg1 is associated with the AKT/mTOR/FoxO signaling pathway.
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PMID:Ginsenoside Rg1 prevents starvation-induced muscle protein degradation via regulation of AKT/mTOR/FoxO signaling in C2C12 myotubes. 2878 21

We have investigated amino acid concentrations and protein metabolism in musculus extensor digitorum longus (EDL, fast-twitch, white muscle) and musculus soleus (SOL, slow-twitch, red muscle) of rats sacrificed in the fed state or after one day of starvation. Fractional protein synthesis rates (FRPS) were measured using the flooding dose method (L-[3,4,5-3H]phenylalanine). Activities of two major proteolytic systems in muscle (the ubiquitin-proteasome and lysosomal) were examined by measurement of chymotrypsin like activity of proteasome (CTLA), expression of ubiquitin ligases atrogin-1 and muscle-ring-finger-1 (MuRF-1), and cathepsin B and L activities. Intramuscular concentrations of the most of non-essential amino acids, FRPS, CTLA and cathepsin B and L activities were in postprandial state higher in SOL when compared with EDL. The differences in atrogin-1 and MuRF-1 expression were insignificant. Starvation decreased concentrations of a number of amino acids and increased concentrations of valine, leucine, and isoleucine in blood plasma. Starvation also decreased intramuscular concentrations of a number of amino acids differently in EDL and SOL, decreased protein synthesis (by 31 % in SOL and 47 % in EDL), and increased expression of atrogin-1 and MuRF-1 in EDL. The effect of starvation on CTLA and cathepsin B and L activities was insignificant. It is concluded that slow-twitch (red) muscles have higher rates of protein turnover and may adapt better to brief starvation when compared to fast-twitch (white) muscles. This phenomenon may play a role in more pronounced atrophy of white muscles in aging and muscle wasting disorders.
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PMID:Amino acid concentrations and protein metabolism of two types of rat skeletal muscle in postprandial state and after brief starvation. 2893 47

Chrysanthemum boreale Makino essential oil (CBMEO) has diverse biological activities including a skin regenerating effect. However, its role in muscle atrophy remains unknown. This study explored the effects of CBMEO and its active ingredients on skeletal muscle atrophy using in vitro and in vivo models of muscle atrophy. CBMEO reversed the size decrease of L6 myoblasts under starvation. Among the eight monoterpene compounds of CBMEO without cytotoxicity for L6 cells, sabinene induced predominant recovery of reductions of myotube diameters under starvation. Sabinene diminished the elevated E3 ubiquitin ligase muscle ring-finger protein-1 (MuRF-1) expression and p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase1/2 (ERK1/2) phosphorylations in starved myotubes. Moreover, sabinene decreased the increased level of reactive oxygen species (ROS) in myotubes under starvation. The ROS inhibitor antagonized expression of MuRF-1 and phosphorylation of MAPKs, which were elevated in starved myotubes. In addition, levels of muscle fiber atrophy and MuRF-1 expression in gastrocnemius from fasted rats were reduced after administration of sabinene. These findings demonstrate that sabinene, a bioactive component from CBMEO, may attenuate skeletal muscle atrophy by regulating the activation mechanism of ROS-mediated MAPK/MuRF-1 pathways in starved myotubes, probably leading to the reverse of reduced muscle fiber size in fasted rats.
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PMID:Sabinene Prevents Skeletal Muscle Atrophy by Inhibiting the MAPK-MuRF-1 Pathway in Rats. 3159 76