Power Output of Fast and Slow Skeletal Muscles of MDX (Dystrophic) and Control Mice After Clenbuterol Treatment

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72380/1/j.1469-445X.2000.02018.x.pd

Expression profiling of skeletal muscle following acute and chronic β2-adrenergic stimulation: implications for hypertrophy, metabolism and circadian rhythm

Background Systemic administration of β-adrenoceptor (β-AR) agonists has been found to induce skeletal muscle hypertrophy and significant metabolic changes. In the context of energy homeostasis, the importance of β-AR signaling has been highlighted by the inability of β1-3-AR-deficient mice to regulate energy expenditure and susceptibility to diet induced obesity. However, the molecular pathways and gene expression changes that initiate and maintain these phenotypic modulations are poorly understood. Therefore, the aim of this study was to identify differential changes in gene expression in murine skeletal muscle associated with systemic (acute and chronic) administration of the β2-AR agonist formoterol. Results Skeletal muscle gene expression (from murine tibialis anterior) was profiled at both 1 and 4 hours following systemic administration of the β2-AR agonist formoterol, using Illumina 46K mouse BeadArrays. Illumina expression profiling revealed significant expression changes in genes associated with skeletal muscle hypertrophy, myoblast differentiation, metabolism, circadian rhythm, transcription, histones, and oxidative stress. Differentially expressed genes relevant to the regulation of muscle mass and metabolism (in the context of the hypertrophic phenotype) were further validated by quantitative RT-PCR to examine gene expression in response to both acute (1-24 h) and chronic administration (1-28 days) of formoterol at multiple timepoints. In terms of skeletal muscle hypertrophy, attenuation of myostatin signaling (including differential expression of myostatin, activin receptor IIB, phospho-Smad3 etc) was observed following acute and chronic administration of formoterol. Acute (but not chronic) administration of formoterol also significantly induced the expression of genes involved in oxidative metabolism, including hexokinase 2, sorbin and SH3 domain containing 1, and uncoupling protein 3. Interestingly, formoterol administration also appeared to influence some genes associated with the peripheral regulation of circadian rhythm (including nuclear factor interleukin 3 regulated, D site albumin promoter binding protein, and cryptochrome 2). Conclusion This is the first study to utilize gene expression profiling to examine global gene expression in response to acute β2-AR agonist treatment of skeletal muscle. In summary, systemic administration of a β2-AR agonist had a profound effect on global gene expression in skeletal muscle. In terms of hypertrophy, β2-AR agonist treatment altered the expression of several genes associated with myostatin signaling, a previously unreported effect of β-AR signaling in skeletal muscle. This study also demonstrates a β2-AR agonist regulation of circadian rhythm genes, indicating crosstalk between β-AR signaling and circadian cycling in skeletal muscle. Gene expression alterations discovered in this study provides insight into many of the underlying changes in gene expression that mediate β-AR induced skeletal muscle hypertrophy and altered metabolism

Muscle-specific deletion of SOCS3 increases the early inflammatory response but does not affect regeneration after myotoxic injury

Myosin heavy chain gene expression and muscle fiber oxidative capacity in muscles from uninjured control and SOCS3 MKO mice. qRT-PCR using primers to detect MyHCIIb (A), MyHCIIx (B), MyHCI (C), and MyHCIIa (D) was performed on RNA extracted from snap frozen muscles following dissection. Data are expressed as mean ± SEM and compared with an unpaired two-tailed Student’s t test. n = 8 mice/genotype. (E) Representative succinate dehydrogenase (SDH)-reacted TA muscle sections from uninjured muscles of 12-week-old control and SOCS3 MKO mice. Quantification of SDH intensity was determined by analysis of SDH reacted TA muscle sections. Data are expressed as mean ± SEM and compared with an unpaired two-tailed Student’s t test. n = 5 mice/genotype. Scale bar = 100 μm. (PDF 145 kb

G-CSF does not influence C2C12 myogenesis despite receptor expression in healthy and dystrophic skeletal muscle

Granulocyte-colony stimulating factor (G-CSF) increases recovery of rodent skeletal muscles after injury, and increases muscle function in rodent models of neuromuscular disease. However, the mechanisms by which G-CSF mediates these effects are poorly understood. G-CSF acts by binding to the membrane spanning G-CSFR and activating multiple intracellular signaling pathways. Expression of the G-CSFR within the haematopoietic system is well known, but more recently it has been demonstrated to be expressed in other tissues. However, comprehensive characterization of G-CSFR expression in healthy and diseased skeletal muscle, imperative before implementing G-CSF as a therapeutic agent for skeletal muscle conditions, has been lacking. Here we show that the G-CSFR is expressed in proliferating C2C12 myoblasts, differentiated C2C12 myotubes, human primary skeletal muscle cell cultures and in mouse and human skeletal muscle. In mdx mice, a model of human Duchenne muscular dystrophy (DMD), G-CSF mRNA and protein was down-regulated in limb and diaphragm muscle, but circulating G-CSF ligand levels were elevated. G-CSFR mRNA in the muscles of mdx mice was up-regulated however steady-state levels of the protein were down-regulated. We show that G-CSF does not influence C2C12 myoblast proliferation, differentiation or phosphorylation of Akt, STAT3, and Erk1/2. Media change alone was sufficient to elicit increases in Akt, STAT3, and Erk1/2 phosphorylation in C2C12 muscle cells and suggest previous observations showing a G-CSF increase in phosphoprotein signaling be viewed with caution. These results suggest that the actions of G-CSF may require the interaction with other cytokines and growth factors in vivo, however these data provides preliminary evidence supporting the investigation of G-CSF for the management of muscular dystrophy

Ageing prolongs inflammatory marker expression in regenerating rat skeletal muscles after injury

<p>Abstract</p> <p>Background</p> <p>Some of the most serious consequences of normal ageing relate to its effects on skeletal muscle, particularly significant wasting and associated weakness, termed "sarcopenia". The underlying mechanisms of sarcopenia have yet to be elucidated completely but an altered muscle inflammatory response after injury is a likely contributing factor. In this study we investigated age-related changes in the expression of numerous inflammatory markers linked to successful muscle regeneration.</p> <p>Methods</p> <p>Right extensor digitorum longus (EDL) muscles from young (3 month), adult (12 month) and old (24 month) male F344 rats were injected with bupivacaine hydrochloride to cause complete muscle fibre degeneration, then excised 12, 24, 36, and 72 hours later (n = 5/age group/time point). We used qRT-PCR to quantify the mRNA expression levels of the inflammatory markers TNFα, IFNγ, IL1, IL18, IL6, and CD18 as well as regenerative markers MyoD and myogenin.</p> <p>Results</p> <p>Inflammatory markers were all increased significantly in all age groups after myotoxic injury. There was a trend for expression of inflammatory markers to be higher in uninjured muscles of old rats, especially at 72 hours post injury where the expression levels of several markers was significantly higher in old compared with young and adult rats. There was also a decrease in the expression of regenerative markers in old rats at 72 hours post injury.</p> <p>Conclusion</p> <p>Our findings identify a prolonged inflammatory signature in injured muscles from old compared with young and adult rats together with a blunted expression of key markers of regeneration in muscles of old rats. Importantly, our findings identify potential targets for future therapeutic strategies for improving the regenerative capacity of skeletal muscle during ageing.</p

Brewing of filter coffee

We report progress on mathematical modelling of coffee grounds in a drip filter coffee machine. The report focuses on the evolution of the shape of the bed of coffee grounds during extraction with some work also carried out on the chemistry of extraction. This work was sponsored by Philips who are interested in understanding an observed correlation between the final shape of the coffee grounds and the quality of the coffee. We used experimental data gathered by Philips and ourselves to identify regimes in the coffee brewing process and relevant regions of parameter space. Our work makes it clear that a number of separate processes define the shape of the coffee bed depending on the values of the parameters involved e.g. the size of the grains and the speed of fluid flow during extraction. We began work on constructing mathematical models of the redistribution of the coffee grounds specialised to each region and on a model of extraction. A variety of analytic and numerical tools were used. Furthermore our research has progressed far enough to allow us to begin to exploit connections between this problem and other areas of science, in particular the areas of sedimentology and geomorphology, where the processes we have observed in coffee brewing have been studied

Force and power output of fast and slow skeletal muscles from mdx mice 6-28 months old

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66165/1/j.1469-7793.2001.00591.x.pd

Glucosinolates from cruciferous vegetables and their potential role in chronic disease: Investigating the preclinical and clinical evidence

An increasing body of evidence highlights the strong potential for a diet rich in fruit and vegetables to delay, and often prevent, the onset of chronic diseases, including cardiometabolic, neurological, and musculoskeletal conditions, and certain cancers. A possible protective component, glucosinolates, which are phytochemicals found almost exclusively in cruciferous vegetables, have been identified from preclinical and clinical studies. Current research suggests that glucosinolates (and isothiocyanates) act via several mechanisms, ultimately exhibiting anti-inflammatory, antioxidant, and chemo-protective effects. This review summarizes the current knowledge surrounding cruciferous vegetables and their glucosinolates in relation to the specified health conditions. Although there is evidence that consumption of a high glucosinolate diet is linked with reduced incidence of chronic diseases, future large-scale placebo-controlled human trials including standardized glucosinolate supplements are needed