Smooth muscle-like Ca2+-regulation of actin-myosin interaction in adult jellyfish striated muscle.

Cnidaria is an animal phylum, whose members probably have the most ancestral musculature. We prepared and characterized, for the first time to our knowledge, native actomyosin from the striated myoepithelium of the adult moon jelly Aurelia sp. The actomyosin contained myosin, paramyosin-like protein, Ser/Thr-kinase, actin, and two isoforms of tropomyosin, but not troponin, which is known to activate contraction dependent on intracellular Ca2+ signaling in almost all striated muscles of bilaterians. Notably, the myosin comprised striated muscle-type heavy chain and smooth muscle-type regulatory light chains. In the presence of Ca2+, the Mg-ATPase activity of actomyosin was stimulated and Ser21 of the regulatory light chain was concomitantly phosphorylated by the addition of calmodulin and myosin light chain kinase prepared from chicken smooth muscle. Collectively, these results suggest that, similar to smooth muscle, the contraction of jellyfish striated muscle is regulated by Ca2+-dependent phosphorylation of the myosin light chain.

Oral collagen-derived dipeptides, prolyl-hydroxyproline and hydroxyprolyl-glycine, ameliorate skin barrier dysfunction and alter gene expression profiles in the skin.

Oral supplementation with collagen hydrolysate (CH) has been shown to improve the condition of the skin in humans and experimental animals. Several hydroxyproline-containing oligo-peptides were previously detected in human peripheral blood after the ingestion of CH, and the two dipeptides, prolyl-hydroxyproline (PO) and hydroxyprolyl-glycine (OG), have been proposed to have beneficial effects on human health. When HR-1 hairless mice were fed a HR-AD diet, which lacked magnesium and zinc, transepidermal water loss (TEWL) increased and water content of stratum corneum decreased. In the present study, we investigated the effects of dietary PO and OG on skin barrier dysfunction in HR-1 hairless mice. Mice were fed a HR-AD diet with or without PO (0.15%) and OG (0.15%) for 35 consecutive days. The administration of PO and OG significantly decreased TEWL, and significantly increased water content of stratum corneum. A DNA microarray analysis of the dorsal skin revealed differences in gene expression between the group administered PO and OG and the control group. We also identified muscle-related Gene Ontology as a result of analyzing the up-regulated genes. These results suggested that the administration of PO and OG improved skin barrier dysfunction and altered muscle-related gene expression.

The effective mechanism of the polysaccharides from Panax ginseng on chronic fatigue syndrome.

Ginseng acidic polysaccharide WGPA isolated from the root of Panax ginseng C. A. Meyer was fractionated into WGPA-A and WGPA-N by anion-exchange chromatography. The antifatigue activity of ginseng acidic polysaccharide WGPA has been reported in our previous research. This present study was designed to identify its active component and elucidate the mechanism for preventing chronic fatigue syndrome (CFS). WGPA, WGPA-A and WGPA-N were orally administered to mice once daily for 15 days. The effects of these compounds on physiological biomarkers of oxidative stress and on the morphology of the mitochondria in striated skeletal muscle were assessed. The results of forced swimming test-induced indicated that WGPA and WGPA-A could lengthen the swimming time, while WGPA-N could not. In addition, malondialdehyde and lactate dehydrogenase levels in serum were enhanced; while those of superoxide dismutase and glutathione peroxidase were lowered. Interestingly, the structural degeneration of mitochondria were all ameliorated. These findings suggested that WGPA-A is the active component of WGPA, it might have potential therapeutic effects for CFS and the oxidative stress might be involved in the pathogenesis. Our results also provided essential data for a better understanding of the antifatigue effects of P. ginseng extracts.

Isoforms of gelsolin from lobster striated muscles differ in calcium-dependence.

Two distinct isoforms of the Ca-dependent actin filament severing protein gelsolin were identified in cross-striated muscles of the American lobster. The variants (termed LG1 and LG2) differ by an extension of 18 AA at the C-terminus of LG1, and by two substitutions at AA735 and AA736, the two C-terminal amino acids of LG2. Functional comparison of the isolated and purified proteins revealed gelsolin-typical properties for both with differences in Ca(2+)-sensitivity, LG2 being activated at significant lower Ca-concentration than LG1: Half maximal activation for both filament severing and G-actin binding was ∼4×10(-7)M Ca(2+) for LG2 vs. ∼2×10(-6)M Ca(2+) for LG1. This indicates a differential activation for the two isoproteins in vivo where they are present in almost equal amounts in the muscle cell. Structure prediction modeling on the basis of the known structure of mammalian gelsolin shows that LG2 lacks the C-terminal alpha-helix which is involved in contact formation between domains G6 and G2. In both mammalian gelsolin and LG1, this "latch bridge" is assumed to play a critical role in Ca(2+)-activation by keeping gelsolin in a closed, inactive conformation at low [Ca(2+)]. In LG2, the reduced contact between G6 and G2 may be responsible for its activation at low Ca(2+)-concentration.

Metabolic changes induced by pre-administration of L-alanyl-glutamine and omega-3 in Wistar rats subjected to sepsis.

PURPOSE: To evaluate the metabolic changes induced by pre-administration of L-alanyl-glutamine (L-Ala-Gln) and omega-3 (ω-3) in rats subjected to sepsis. METHODS: Eighteen male Wistar rats were randomized into three groups (n=6) and treated with saline (group Control-G-1), L-Ala-Gln (0.75 mg /kg , G-2) or ω-3 (0.2 g /kg, G-3 ) administered intravenously 3, 2 and 1 day and 30 minutes before induction of sepsis. Samples (blood, striated muscle and liver) were collected 48 hours after induction of sepsis, to measure the concentrations of metabolites (pyruvate, lactate, glucose and ketone bodies. RESULTS: There was a significant increase in muscle glycolysis and gluconeogenesis in the liver in rats treated with L-Ala-Gln and ω-3, compared to the control group, 48 hours after induction of sepsis. CONCLUSION: Pre-administration of L-Ala-Gln or ω-3 to rats subjected to sepsis resulted in similar metabolic changes, by rising glycolysis in peripheral tissues and stimulating hepatic gluconeogenesis and ketogenesis, resulting in increased energy supply to septic rats.

Metabolic changes induced by pre-administration of L-alanyl-glutamine and Omega-3 in Wistar rats subjected to sepsis / Alterações metabólicas induzidas pela pré-administração de L-alanil-glutamina e ômega-3 em ratos Wistar submetidos à sepse

PURPOSE: To evaluate the metabolic changes induced by pre-administration of L-alanyl-glutamine (L-Ala-Gln) and omega-3 (ω-3) in rats subjected to sepsis. METHODS: Eighteen male Wistar rats were randomized into three groups (n=6) and treated with saline (group Control-G-1), L-Ala-Gln (0.75 mg /kg , G-2) or ω-3 (0.2 g /kg, G-3 ) administered intravenously 3, 2 and 1 day and 30 minutes before induction of sepsis. Samples (blood, striated muscle and liver) were collected 48 hours after induction of sepsis, to measure the concentrations of metabolites (pyruvate, lactate, glucose and ketone bodies. RESULTS: There was a significant increase in muscle glycolysis and gluconeogenesis in the liver in rats treated with L-Ala-Gln and ω-3, compared to the control group, 48 hours after induction of sepsis. CONCLUSION: Pre-administration of L-Ala-Gln or ω-3 to rats subjected to sepsis resulted in similar metabolic changes, by rising glycolysis in peripheral tissues and stimulating hepatic gluconeogenesis and ketogenesis, resulting in increased energy supply to septic rats.

OBJETIVO: Avaliar as alterações metabólicas induzidas pela pré-administração de L-alanil-glutamina (L-Ala-Gln) e ômega-3 (ω-3) em ratos Wistar submetidos à sepse. MÉTODOS: Dezoito ratos machos Wistar, randomizados em três grupos iguais (n=6) e tratados com solução salina (grupo Controle-G-1), L-Ala-Gln (0,75mg/Kg) ou ω-3 (0,2g/Kg) por via endovenosa administrados 3, 2 e 1 dia e 30 minutos antes da indução do estado de sepse. Amostras (sangue, músculo estriado e fígado) foram coletadas 48 horas após indução da sepse, para dosagem das concentrações de metabólitos (piruvato, lactato, glicose e corpos cetônicos). RESULTADOS: Houve aumento significante da glicólise no músculo e da gliconeogênese no fígado nos ratos tratados com L-Ala-Gln e ω-3, comparados ao controle, 48 horas após a indução da sepse. CONCLUSÃO: A pré-administração de L-Ala-Gln ou ω-3 em ratos submetidos à sepse resultou em alterações metabólicas semelhantes, com aumento da glicólise nos tecidos periféricos e da gliconeogênese hepática e cetogênese, aumentando a oferta de energia disponível.

Getting to the meat of the matter: beyond protein supplementation in maintenance dialysis.

Until recently, patients on dialysis with low serum albumin levels were characterized as suffering from protein malnutrition suggesting that the cause of this malady was due to an inadequate intake of protein. In fact, these patients tend to suffer from a wasting syndrome similar to cachexia commonly associated with inflammation in which there is loss of lean body mass and fat mass is underutilized. The term protein energy wasting has been used to characterize this syndrome and suggests that the simple addition of protein supplements to the dietary regimen of hemodialysis patients will not cure this malady. Correction of the underlying inflammatory disorder which drives losses of body protein and fuel reserves is far more important and is the single most effective therapy. Protein supplements which may promote albumin synthesis and synthesis of liver-related proteins tend to increase muscle catabolism. Muscle growth is not fostered by increasing dietary protein above recommended goals for dialysis patients, but can be promoted by the addition of protein of high biological value that is rich in leucine and other essential amino acids in tandem with repetitive exercises. Ultimately, correction of PEW hinges on the diagnosis and treatment of co-morbid conditions in combination with strategies to replenish caloric and protein stores. A supplementary exercise program would allow recovery of lean body mass. Given the multiple co-morbidities that exist in this population, therapy would have to be individualized.

Coenzyme Q10 and vitamin E deficiency in Friedreich's ataxia: predictor of efficacy of vitamin E and coenzyme Q10 therapy.

BACKGROUND AND PURPOSE: A pilot study of high dose coenzyme Q(10) (CoQ(10))/vitamin E therapy in Friedreich's ataxia (FRDA) patients resulted in significant clinical improvements in most patients. This study investigated the potential for this treatment to modify clinical progression in FRDA in a randomized double blind trial. METHODS: Fifty FRDA patients were randomly divided into high or low dose CoQ(10)/ vitamin E groups. The change in International Co-operative Ataxia Ratings Scale (ICARS) was assessed over 2 years as the primary end-point. A post hoc analysis was made using cross-sectional data. RESULTS: At baseline serum CoQ(10) and vitamin E levels were significantly decreased in the FRDA patients (P < 0.001). During the trial CoQ(10) and vitamin E levels significantly increased in both groups (P < 0.01). The primary and secondary end-points were not significantly different between the therapy groups. When compared to cross-sectional data 49% of all patients demonstrated improved ICARS scores. This responder group had significantly lower baseline serum CoQ(10) levels. CONCLUSIONS: A high proportion of FRDA patients have a decreased serum CoQ(10) level which was the best predictor of a positive clinical response to CoQ(10)/vitamin E therapy. Low and high dose CoQ(10)/vitamin E therapies were equally effective in improving ICARS scores.