Dietary L-Arginine Supplementation Affects the Skeletal Longissimus Muscle Proteome in Finishing Pigs

Forty-eight Duroc x Landrace x Large White gilts were used to determine the relationship between proteome changes of longissimus muscle and intramuscular fat (IMF) content in arginine-supplemented pigs. Beginning at 60 kg BW, pigs were fed a corn- and soybean meal-based diet supplemented or not with 1% L-arginine until they reached a BW of 100 kg. Supplementation with 1% L-arginine did not affect the growth performance or carcass traits, while it increased IMF content by 32% (P < 0.01), it also decreased the drip loss at 48 h post-mortem and the b* meat color value at 24 h post-mortem; supplementation with 1% dietary L-arginine did not change the proportion of SFA and MUFA in muscle lipids. The proteome changes in longissimus muscle between the control and supplemented pigs showed that L-arginine significantly influenced the abundance of proteins related to energy metabolism, fiber type and structure. The increase in IMF content was positively correlated with the increased abundance of slow twitch troponin I (TNNI1) protein and negatively correlated with myosin heavy chain IIb (MyHC IIb) protein content. It is suggested that the proteome changes in longissimus muscle contributed to the greater IMF content in L-arginine supplemented pigs.     

Hypophosphatemia Induced by Dietary Aluminium Hydroxide Supplementation in Growing Pigs: Effects on Erythrocytes,Myocardium, Skeletal Muscle and Liver

Three groups of pigs were studied during and after 10 weeks of treatment with either Al(OH)3 (Al[OH]3-group, n=8) to induce hypophosphatemia, A1P04 (AlP04-group, n=8, aluminium control without hypophosphatemia) or no addition to the feed (control group, n=8). Blood samples were taken at the start of the experiment and after 3, 6 and 10 weeks and were analyzed for phosphate, calcium and 2,3-diphosphoglycerate (2,3-DPG). Samples from myocardium, skeletal muscle and liver were obtained in connection with exsanguination and analyzed for glycogen, adenosine-tri-phosphate (ATP), creatine phosphate (CP), glucose-6-phosphate (G-6-P) and lactate. The Al(OH)3-group became hypophosphatemic and hypercalcémie with low levels of 2,3-DPG in erythrocytes within 3 weeks and showed a retarded growth rate. After 10 weeks the Al(OH)3-group had low levels of ATP in myocardium as compared with the control-group and low levels of G-6-P as compared with the AlP04-group. No disturbances on electro-cardiograms registered at rest could be documented. G-6-P concentration was low in the biceps muscle in the Al(OH)3-group as compared with the AlP04-group and in the liver low G-6-P concentration was seen in addition to high lactate concentration. The fibre type composition in M. Longissimus did not differ between groups, but the Al(OH)3-group had, due to retardation in growth, smaller mean fibre-areas than pigs in the AlP04-group. Hypophosphatemia gave rise to high serum calcium levels, low concentration of 2,3-DPG in erythrocytes and influenced G-6-P concentration in skeletal muscle, G-6-P and ATP in myocardium, G-6-P and lactate in liver. Retarded growth was one serious consequence of hypophosphatemia and the disturbed energy metabolism.     

Effects of Added Zinc on Skeletal Muscle Morphometrics and Gene Expression of Finishing Pigs Fed Ractopamine-HCL

Finishing pigs (n = 320) were used in a 35-day study to determine the effects of ractopamine-HCl (RAC) and supplemental Zinc (Zn) level on loin eye area (LEA) and gene expression. Pens were randomly allotted to the following treatments for the final 35 days on feed: a corn-soybean meal diet (CON), a diet with 10 ppm RAC (RAC+), and RAC diet plus added Zn at 75, 150, or 225 ppm. Sixteen pigs per treatment were randomly selected for collection of serial muscle biopsies and carcass data on day 0, 8, 18, and 32 of the treatment phase. Compared to CON carcasses, RAC+ carcasses had 12.6% larger (P = 0.03) LEA. Carcasses from RAC diets with added Zn had a tendency for increased (quadratic, P < 0.10) LEA compared to the RAC+ carcasses. Compared to RAC+ pigs, relative expression of IGF1 decreased with increasing levels of Zn on day 8 and 18 of treatment, but expression levels were similar on day 32 due to Zn treatments increasing in expression while the RAC+ treatment decreased (Zn quadratic × day quadratic, P = 0.04). A similar trend was detected for the expression of β₁-receptor where expression levels in the RAC+ pigs were greater than Zn supplemented pigs on day 8 and 18 of the experiment, but the magnitude of difference between the treatments was reduced on day 32 due to a decrease in expression by RAC+ pigs and an increase in expression by the Zn pigs (Zn quadratic × day quadratic, P = 0.01). The ability of Zn to prolong the expression of these two genes may be responsible for the tendency of Zn to increase LEA in RAC supplemented pigs.     

Efficacy of Dietary Chromium (III) Supplementation on Tissue Chromium Deposition in Finishing Pigs

The study was conducted to evaluate the efficacy of different forms of trivalent chromium (Cr) supplementation on tissue chromium deposition in finishing pigs. A total of 96 pigs with an initial average body mass 65.57±1.05 kg were blocked by body mass and randomly assigned to four treatments with three replicates. Pigs were offered one of four diets including a control diet or the control diet supplemented with 200 μg/kg chromium from either chromium chloride (CrCl(3)), chromium picolinate (CrPic) or chromium nanocomposite (CrNano) for 40 days. During the trial, all pigs were given free access to feed and water. After feeding trial, eight pigs from each treatment were slaughtered for samples collection. The results showed that supplemental CrNano increased Cr content in blood, longissimus muscle, heart, liver, kidney, jejunum, and ileum (P<0.05). Supplemental Cr from three sources increased Cr excretion from all feces (P<0.05). Urinary Cr excretion was increased by CrNano or CrPic supplementation significantly. These results suggested that chromium nanocomposite exhibited more effective on tissue Cr deposition in pigs, which indicated higher absorption compared with CrCl(3) and CrPic.     

Glutamine Supplementation Stimulates Protein-Synthetic and Inhibits Protein-Degradative Signaling Pathways in Skeletal Muscle of Diabetic Rats

In this study, we investigated the effect of glutamine (Gln) supplementation on the signaling pathways regulating protein synthesis and protein degradation in the skeletal muscle of rats with streptozotocin (STZ)-induced diabetes. The expression levels of key regulatory proteins in the synthetic pathways (Akt, mTOR, GSK3 and 4E-BP1) and the degradation pathways (MuRF-1 and MAFbx) were determined using real-time PCR and Western blotting in four groups of male Wistar rats; 1) control, non-supplemented with glutamine; 2) control, supplemented with glutamine; 3) diabetic, non-supplemented with glutamine; and 4) diabetic, supplemented with glutamine. Diabetes was induced by the intravenous injection of 65 mg/kg bw STZ in citrate buffer (pH 4.2); the non-diabetic controls received only citrate buffer. After 48 hours, diabetes was confirmed in the STZ-treated animals by the determination of blood glucose levels above 200 mg/dL. Starting on that day, a solution of 1 g/kg bw Gln in phosphate buffered saline (PBS) was administered daily via gavage for 15 days to groups 2 and 4. Groups 1 and 3 received only PBS for the same duration. The rats were euthanized, and the soleus muscles were removed and homogenized in extraction buffer for the subsequent measurement of protein and mRNA levels. The results demonstrated a significant decrease in the muscle Gln content in the diabetic rats, and this level increased toward the control value in the diabetic rats receiving Gln. In addition, the diabetic rats exhibited a reduced mRNA expression of regulatory proteins in the protein synthesis pathway and increased expression of those associated with protein degradation. A reduction in the skeletal muscle mass in the diabetic rats was observed and was alleviated partially with Gln supplementation. The data suggest that glutamine supplementation is potentially useful for slowing the progression of muscle atrophy in patients with diabetes.     

Effects of Dietary Energy Sources on Post Mortem Glycolysis,Meat Quality and Muscle Fibre Type Transformation of Finishing Pigs

Dietary energy source can influence muscle glycogen storage at slaughter. However, few studies have demonstrated whether the diet-induced change of muscle glycogen is achieved by the transformation of muscle fibre type. This study investigated the effects of dietary energy sources on meat quality, post mortem glycolysis and muscle fibre type transformation of finishing pigs. Seventy-two barrows with an average body weight of 65.0 ± 2.0 kg were selected and were allotted to three iso-energetic and iso-nitrogenous diets A, B or C, and each treatment consisted of three replicates (pens) of eight pigs each. Diet A contained 44.1% starch, 5.9% crude fat and 12.6% neutral detergent fiber (NDF); diet B contained 37.6% starch, 9.5% crude fat and 15.4% NDF; and diet C contained 30.9% starch, 14.3% crude fat and 17.8% NDF. The duration of the experiment was 28 days. After feed withdrawal 12 h, 24 pigs (eight per treatment) were slaughtered, samples from M. longissimus lumborum (LL) were collected for subsequent analysis. The results showed that pigs fed diet C had lesser average daily gain, average daily feed intake and back fat depth than those fed diet A (P<0.05). Diet C increased pH_45min (P<0.05) and decreased drip loss (P<0.05) in LL muscles compared with diet A. Meat from pigs fed diet A showed increased contents of lactate and greater glycolytic potential (GP) compared with those fed diet C (P<0.05). Greater mRNA expression of myosin heavy-chain (MyHC)-I and IIa and lesser expression of MyHC-IIx and IIb (P<0.05) in LL muscles were found in pigs fed diet C, than in pigs fed diet A. In addition, pigs fed diet C resulted in downregulation of miR23a and upregulation of miR409 and miR208b (P<0.05), associated with conserved changes of their corresponding targets. These findings indicated that diets containing low starch and high fibre were beneficial in reducing muscle glycolysis, improving meat quality of finishing pigs. This reduction of GP may be partially associated with the improvement of oxidative fibre composition in LL muscle, and the change in myofibre type may be correlated with the change in the miRNA expression.     

Effects of Long Term Supplementation of Anabolic Androgen Steroids on Human Skeletal Muscle

The effects of long-term (over several years) anabolic androgen steroids (AAS) administration on human skeletal muscle are still unclear. In this study, seventeen strength training athletes were recruited and individually interviewed regarding self-administration of banned substances. Ten subjects admitted having taken AAS or AAS derivatives for the past 5 to 15 years (Doped) and the dosage and type of banned substances were recorded. The remaining seven subjects testified to having never used any banned substances (Clean). For all subjects, maximal muscle strength and body composition were tested, and biopsies from the vastus lateralis muscle were obtained. Using histochemistry and immunohistochemistry (IHC), muscle biopsies were evaluated for morphology including fiber type composition, fiber size, capillary variables and myonuclei. Compared with the Clean athletes, the Doped athletes had significantly higher lean leg mass, capillary per fibre and myonuclei per fiber. In contrast, the Doped athletes had significantly lower absolute value in maximal squat force and relative values in maximal squat force (relative to lean body mass, to lean leg mass and to muscle fiber area). Using multivariate statistics, an orthogonal projection of latent structure discriminant analysis (OPLS-DA) model was established, in which the maximal squat force relative to muscle mass and the maximal squat force relative to fiber area, together with capillary density and nuclei density were the most important variables for separating Doped from the Clean athletes (regression  =  0.93 and prediction  =  0.92, p<0.0001). In Doped athletes, AAS dose-dependent increases were observed in lean body mass, muscle fiber area, capillary density and myonuclei density. In conclusion, long term AAS supplementation led to increases in lean leg mass, muscle fiber size and a parallel improvement in muscle strength, and all were dose-dependent. Administration of AAS may induce sustained morphological changes in human skeletal muscle, leading to physical performance enhancement.     

日粮蛋白质水平对断奶仔猪肠道发育的影响

实验研究了饲粮不同粗蛋白水平对断奶仔猪肠黏膜形态和肠道健康状况的影响.实验采用完全随机设计,将72头28日龄断奶的仔猪分为4组,每组3个重复,每个重复6头.4个组分别接受24%、22%、20%、18%蛋白水平的日粮.结果表明,采食粗蛋白水平为24%的日粮使小肠不同肠段绒毛的生长受到了抑制,使隐窝加深、绒毛/隐窝比降低;随着日粮粗蛋白水平的下降,回肠和盲肠消化物pH、氨氮浓度显著降低(P<0.05),盲肠消化物中腐胺浓度显著降低(P<0.01).采食粗蛋白水平为24%的仔猪有轻度腹泻现象.上述结果提示,适当降低断奶仔猪日粮粗蛋白水平并平衡主要必需氨基酸,有利于降低肠道有害菌群的增殖,改善肠道健康状况.     

Effects of Dietary Eicosapentaenoic Acid (EPA) Supplementation in High-Fat Fed Mice on Lipid Metabolism and Apelin/APJ System in Skeletal Muscle

Various studies have shown that eicosapentaenoic acid (EPA) has beneficial effects on obesity and associated disorders. Apelin, the ligand of APJ receptor also exerts insulin-sensitizing effects especially by improving muscle metabolism. EPA has been shown to increase apelin production in adipose tissue but its effects in muscle have not been addressed. Thus, the effects of EPA supplementation (36 g/kg EPA) in high-fat diet (HFD) (45% fat, 20% protein, 35% carbohydrate) were studied in mice with focus on muscle lipid metabolism and apelin/APJ expression. Compared with HFD mice, HFD+EPA mice had significantly less weight gain, fat mass, lower blood glucose, insulinemia and hepatic steatosis after 10 weeks of diet. In addition, EPA prevented muscle metabolism alterations since intramuscular triglycerides were decreased and β-oxidation increased. In soleus muscles of HFD+EPA mice, apelin and APJ expression were significantly increased compared to HFD mice. However, plasma apelin concentrations in HFD and HFD+EPA mice were similar. EPA-induced apelin expression was confirmed in differentiated C2C12 myocytes but in this model, apelin secretion was also increased in response to EPA treatment. In conclusion, EPA supplementation in HFD prevents obesity and metabolic alterations in mice, especially in skeletal muscle. Since EPA increases apelin/APJ expression in muscle, apelin may act in a paracrine/autocrine manner to contribute to these benefical effects.     

Effects of Corticosterone on Connectin Content and Protein Breakdown in Rat Skeletal Muscle

We examined the effects of a glucocorticoid, corticosterone, on calpain activity, connectin content and protein breakdown in rat muscle. The results indicated that calpain activity was increased by corticosterone and thus breakdown of connectin was stimulated followed by increased breakdown of skeletal muscle protein.     

Autophagy Signaling in Skeletal Muscle of Infarcted Rats

Background

Heart failure (HF)-induced skeletal muscle atrophy is often associated to exercise intolerance and poor prognosis. Better understanding of the molecular mechanisms underlying HF-induced muscle atrophy may contribute to the development of pharmacological strategies to prevent or treat such condition. It has been shown that autophagy-lysosome system is an important mechanism for maintenance of muscle mass. However, its role in HF-induced myopathy has not been addressed yet. Therefore, the aim of the present study was to evaluate autophagy signaling in myocardial infarction (MI)-induced muscle atrophy in rats.

Methods/Principal Findings

Wistar rats underwent MI or Sham surgeries, and after 12 weeks were submitted to echocardiography, exercise tolerance and histology evaluations. Cathepsin L activity and expression of autophagy-related genes and proteins were assessed in soleus and plantaris muscles by fluorimetric assay, qRT-PCR and immunoblotting, respectively. MI rats displayed exercise intolerance, left ventricular dysfunction and dilation, thereby suggesting the presence of HF. The key findings of the present study were: a) upregulation of autophagy-related genes (GABARAPL1, ATG7, BNIP3, CTSL1 and LAMP2) was observed only in plantaris while muscle atrophy was observed in both soleus and plantaris muscles, and b) Cathepsin L activity, Bnip3 and Fis1 protein levels, and levels of lipid hydroperoxides were increased specifically in plantaris muscle of MI rats.

Conclusions

Altogether our results provide evidence for autophagy signaling regulation in HF-induced plantaris atrophy but not soleus atrophy. Therefore, autophagy-lysosome system is differentially regulated in atrophic muscles comprising different fiber-types and metabolic characteristics.     

Effect of L-Carnitine Supplementation on Utilisation of Energy and Protein in Broiler Chicken Fed Different Dietary Fat Levels

Effects of a supplementation of 80mg L-carnitine perkg diet were studied in broiler chicken at two dietary levels of fat (4 and 8 %) and different feeding levels (ad libitum in a growth trial, 95 and 85 % of ad libitum in a balance trial). A low-carnitine basal diet adequate in amino acid concentration was used. In the growth trial, each diet was fed to 9 groups of 10 birds each for 16 days from day 5 of live onwards. Growth and feed intake were determined. At the end of the trial, birds were killed and homogenised for subsequent empty body analysis. Accretion of protein and energy was determined using a representative blank group killed at the beginning of the trial. In the balance trial, 8 individual birds were used per treatment. Birds were offered the feed at approximately 85 and 95% of ad libitum intake, which was determined with separate birds for both fat levels. Excreta were quantitatively collected three times daily for 8 consecutive days beginning on day 17 individually for each bird. Supplemented L-carnitine did not significantly affect any response criterion. However, growth and feed conversion tended to be improved by about 5% in the carnitine supplemented diets when fed ad libitum. An interaction between carnitine and fat level occurred with regard to feed conversion, indicating that carnitine had a positive effect at the high fat level, but not at the low fat level. L-carnitine did not positively affect the metabolisability of energy (ME/GE) and the efficiency of energy utilisation (RE/GE or RE/ME). Similarly, no significant carnitine effect was determined with regard to N accretion and the efficiency of utilisation of dietary protein in both trials. It is concluded that endogenous carnitine synthesis is not the limiting factor for energy utilisation in broiler chicken, even at high dietary fat concentration. Occasionally reported positive effects of supplemental carnitine were likewise caused by reasons other than improved energy or protein utilisation. Further studies on amino acid utilisation and catabolism should consider marginal amino acid supply.     

Role and Metabolism of Free Leucine in Skeletal Muscle in Protein Sparing Action of Dietary Carbohydrate and Fat

Feeding rats with either a carbohydrate meal or a fat meal to the previously fasted rats caused significant decrease in urinary output of urea and total nitrogen. The content of free leucine in skeletal muscle decreased in the rats fed either a carbohydrate meal or a fat meal. Feeding of either a carbohydrate meal or a fat meal stimulated incoiporation of l-leucine-1–¹⁴C into protein fraction of skeletal muscle and reduced its oxidation to ¹⁴CO₂.

These results suggest that the metabolism of leucine is under nutritional regulation and that the decrease in content of free leucine in skeletal muscle might be caused by enhanced reutilization of leucine into protein by the feeding of a carbohydrate meal or a fat meal. The role of free leucine in skeletal muscle as a regulator of protein turnover in the tissue are discussed in relation to the metabolism of this branched chain amino acid.     

Defective Dietary Induction of Uncoupling Protein 3 in Skeletal Muscle of Obesity‐Prone Rats

Objective: The goal of this study was to determine whether differential induction of skeletal muscle uncoupling protein 3 (UCP3) contributes to the development of diet‐induced obesity (DIO) or resistance to the development of obesity (DR) when rats are placed on a moderate fat (31%) high energy (HE) diet. Research Methods and Procedures: Gastrocnemius muscle was obtained from Sprague‐Dawley rats that were identified as DIO‐prone (n = 5) or DR (n = 5) on the basis of urinary norepinephrine excretion while consuming a chow diet. Muscle was also obtained from animals in the top tertile of weight gain (DIO_HE, n = 5) and the bottom tertile of weight gain (DR_HE, n = 5) after 2 weeks on the HE diet. UCP3 and actin mRNA levels were measured in all muscle samples by Northern analysis. To distinguish the effect of dietary energy content from the effect of obesity itself, we studied additional DIO and DR animals that had been returned to a chow diet for 10 weeks after consuming a HE diet for 10 weeks. Results: The muscle UCP3/actin mRNA ratio in animals that resisted the development of obesity during 2 weeks on the HE diet was 3‐fold higher than in the other groups (DR_HE = 3.24 ± 0.83, DIO_HE = 0.91 ± 0.20, DIO‐prone = 0.72 ± 0.15, DR = 0.63 ± 0.15; p = 0.002). However, there was no difference in muscle UCP3/actin mRNA ratios between DIO animals and DR animals that had been fed the HE diet for 10 weeks and then returned to either an ad libitum chow diet for 10 weeks (DIO = 13.8 ± 3.53, DR = 11.1 ± 3.43, p = NS) or to a restricted chow diet for 10 weeks (DIO = 11.0 ± 2.85, DR = 10.6 ± 2.20, p = NS) despite significantly greater body weight of the DIO animals. Discussion: DR animals may initially resist weight gain when placed on a HE diet through a greater induction of muscle UCP3. This induction is transient and is related more closely to dietary fat content than to body fat stores. DIO animals show no initial induction of muscle UCP3, which may contribute to their increased metabolic efficiency soon after exposure to a HE diet.     

Gestational Diabetes Is Characterized by Reduced Mitochondrial Protein Expression and Altered Calcium Signaling Proteins in Skeletal Muscle

The rising prevalence of gestational diabetes mellitus (GDM) affects up to 18% of pregnant women with immediate and long-term metabolic consequences for both mother and infant. Abnormal glucose uptake and lipid oxidation are hallmark features of GDM prompting us to use an exploratory proteomics approach to investigate the cellular mechanisms underlying differences in skeletal muscle metabolism between obese pregnant women with GDM (OGDM) and obese pregnant women with normal glucose tolerance (ONGT). Functional validation was performed in a second cohort of obese OGDM and ONGT pregnant women. Quantitative proteomic analysis in rectus abdominus skeletal muscle tissue collected at delivery revealed reduced protein content of mitochondrial complex I (C-I) subunits (NDUFS3, NDUFV2) and altered content of proteins involved in calcium homeostasis/signaling (calcineurin A, α1-syntrophin, annexin A4) in OGDM (n = 6) vs. ONGT (n = 6). Follow-up analyses showed reduced enzymatic activity of mitochondrial complexes C-I, C-III, and C-IV (−60–75%) in the OGDM (n = 8) compared with ONGT (n = 10) subjects, though no differences were observed for mitochondrial complex protein content. Upstream regulators of mitochondrial biogenesis and oxidative phosphorylation were not different between groups. However, AMPK phosphorylation was dramatically reduced by 75% in the OGDM women. These data suggest that GDM is associated with reduced skeletal muscle oxidative phosphorylation and disordered calcium homeostasis. These relationships deserve further attention as they may represent novel risk factors for development of GDM and may have implications on the effectiveness of physical activity interventions on both treatment strategies for GDM and for prevention of type 2 diabetes postpartum.     

mTOR介导的骨骼肌蛋白质翻译调控

胰岛素、氨基酸和力量运动刺激信号转导的共同终点是蛋白激酶mTOR.mTOR及其下游靶标在调控蛋白质合成过程中起着中枢作用.研究mTOR的上游和下游事件将有助于进一步了解骨骼肌内蛋白质合成及肥大的机制.更进一步详细研究不同组合(营养和力量运动)引起的骨骼肌内mTOR信号通路的变化特征有着更重要的实际意义.     

Nexilin,a Cardiomyopathy-Associated F-Actin Binding Protein,Binds and Regulates IRS1 Signaling in Skeletal Muscle Cells

Insulin stimulates glucose uptake through a highly organized and complex process that involves movement of the glucose transporter 4 (GLUT4) from intracellular storage sites to the plasma membrane. Previous studies in L6 skeletal muscle cells have shown that insulin-induced activation and assembly of insulin receptor substrate 1 (IRS1) and p85α the regulatory subunit of the Type 1A phosphatidylinositol-3-kinase (PI3K), within remodeled actin-rich membrane structures is critical for downstream signalling mediating the translocation of GLUT4. The mechanism for localization within actin cytoskeletal scaffolds is not known, as direct interaction of IRS1 or p85α with F-actin has not been demonstrated. Here we show that nexilin, a F-actin binding protein implicated in the pathogenesis of familial dilated cardiomyopathies, preferentially binds to IRS1 over IRS2 to influence glucose transport in skeletal muscle cells. Nexilin stably associates with IRS1 under basal conditions in L6 myotubes and this complex is disassembled by insulin. Exposure of L6 myotubes to Latrunculin B disrupts the spatial patterning of nexilin and its transient association with IRS1. Functional silencing of nexilin has no effect on insulin-stimulated IRS1 tyrosine phosphorylation, however it enhances recruitment of p85α to IRS1 resulting in increased PI-3, 4, 5-P₃ formation, coincident with enhanced AKT activation and glucose uptake. By contrast, overexpression of nexilin inhibits transmission of IRS1 signals to AKT. Based on these findings we propose that nexilin may tether IRS1 to actin-rich structures under basal conditions, confining IRS1 signaling to specific subcellular locations in the cell. Insulin-elicited release of this constraint may enhance the efficiency of IRS1/PI3K interaction and PI-3, 4, 5-P₃ production at localized sites. Moreover, the selective binding of nexilin to IRS1 and not IRS2 may contribute to the differential specificity of IRS isoforms in the modulation of GLUT4 trafficking in skeletal muscle cells.     

Muscle Atrophy in Response to Cytotoxic Chemotherapy Is Dependent on Intact Glucocorticoid Signaling in Skeletal Muscle

Cancer cachexia is a syndrome of weight loss that results from the selective depletion of skeletal muscle mass and contributes significantly to cancer morbidity and mortality. The driver of skeletal muscle atrophy in cancer cachexia is systemic inflammation arising from both the cancer and cancer treatment. While the importance of tumor derived inflammation is well described, the mechanism by which cytotoxic chemotherapy contributes to cancer cachexia is relatively unexplored. We found that the administration of chemotherapy to mice produces a rapid inflammatory response. This drives activation of the hypothalamic-pituitary-adrenal axis, which increases the circulating level of corticosterone, the predominant endogenous glucocorticoid in rodents. Additionally, chemotherapy administration results in a significant loss of skeletal muscle mass 18 hours after administration with a concurrent induction of genes involved with the ubiquitin proteasome and autophagy lysosome systems. However, in mice lacking glucocorticoid receptor expression in skeletal muscle, chemotherapy-induced muscle atrophy is completely blocked. This demonstrates that cytotoxic chemotherapy elicits significant muscle atrophy driven by the production of endogenous glucocorticoids. Further, it argues that pharmacotherapy targeting the glucocorticoid receptor, given in concert with chemotherapy, is a viable therapeutic strategy in the treatment of cancer cachexia.     

Influence of the Dietary Protein Deficiency on the Protein Synthetic Activity of Microsome and Soluble Fraction from Muscle and Liver of Rats

Phytochromes are photoreceptors that regulate many aspects of plant growth and development in response to red/far-red light signals from the environment. In this study, we analyzed chromophore ligation and photochromism of missense phytochrome mutants in the Per-Arnt-Sim (PAS)-related domain (PRD). Among the 14 mutants analyzed, the Gly768Asp mutant of Avena phytochrome A showed aberrant photochromism and dark reversion, suggesting that amino acid residues in the C-terminal domain affect the photochemical properties of the photosensory N-terminal domain.