The Experts below are selected from a list of 3336 Experts worldwide ranked by ideXlab platform
Aaron P Russell - One of the best experts on this subject based on the ideXlab platform.
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influence of divergent exercise contraction mode and whey protein supplementation on Atrogin 1 murf1 and foxo1 3a in human skeletal muscle
Journal of Applied Physiology, 2014Co-Authors: Renae J Stefanetti, Aaron P Russell, Severine Lamon, Stine Klejs Rahbek, Jean Farup, Evelyn Zacharewicz, Marita A Wallace, Mikkel H Vendelbo, Kristian VissingAbstract:Knowledge from human exercise studies on regulators of muscle atrophy is lacking, but it is important to understand the underlying mechanisms influencing skeletal muscle protein turnover and net protein gain. This study examined the regulation of muscle atrophy–related factors, including Atrogin-1 and MuRF1, their upstream transcription factors FOXO1 and FOXO3A and the Atrogin-1 substrate eIF3-f, in response to unilateral isolated eccentric (ECC) vs. concentric (CONC) exercise and training. Exercise was performed with whey protein hydrolysate (WPH) or isocaloric carbohydrate (CHO) supplementation. Twenty-four subjects were divided into WPH and CHO groups and completed both single-bout exercise and 12 wk of training. Single-bout ECC exercise decreased Atrogin-1 and FOXO3A mRNA compared with basal and CONC exercise, while MuRF1 mRNA was upregulated compared with basal. ECC exercise downregulated FOXO1 and phospho-FOXO1 protein compared with basal, and phospho-FOXO3A was downregulated compared with CONC. CON...
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androgenic and estrogenic regulation of Atrogin 1 murf1 and myostatin expression in different muscle types of male mice
European Journal of Applied Physiology, 2014Co-Authors: H De Naeyer, Aaron P Russell, Severine Lamon, Inge Everaert, A De Spaey, Bert Vanheel, Youri Taes, Wim DeraveAbstract:The molecular factors targeted by androgens and estrogens on muscle mass are not fully understood. The current study aimed to explore gene and protein expression of Atrogin-1, MuRF1, and myostatin in an androgen deprivation-induced muscle atrophy model. We examined the effects of Orx either with or without testosterone (T) or estradiol (E2) administration on Atrogin-1 gene expression, and MuRF1 and myostatin gene and protein expression. Measurements were made in soleus (SOL), extensor digitorum longus (EDL) and levator ani/bulbocavernosus (LA/BC) of male C57BL/6 mice. Thirty days of Orx resulted in a reduction in weight gain and muscle mass. These effects were prevented by T. In LA/BC, Atrogin-1 and MuRF1 mRNA was increased throughout 30 days of Orx, which was fully reversed by T and partially by E2 administration. In EDL and SOL, a less pronounced upregulation of both genes was only detectable at the early stages of Orx. Myostatin mRNA levels were downregulated in LA/BC and upregulated in EDL following Orx. T, but not E2, reversed these effects. No changes in protein levels of MuRF1 and myostatin were found in EDL at any time point following Orx. The atrophy in SOL and EDL in response to androgen deprivation, and its restoration by T, is accompanied by only minimal changes in atrogenes and myostatin gene expression. The marked differences in muscle atrophy and atrogene and myostatin mRNA between LA/BC and the locomotor muscles suggest that the murine LA/BC is not an optimal model to study Orx-induced muscle atrophy.
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the role and regulation of mafbx Atrogin 1 and murf1 in skeletal muscle atrophy
Pflügers Archiv: European Journal of Physiology, 2011Co-Authors: Victoria C Foletta, Lloyd J White, Amy E Larsen, Bertrand Leger, Aaron P RussellAbstract:Skeletal muscle atrophy occurs in many chronic diseases and disuse conditions. Its severity reduces patient recovery, independence and quality of life. The discovery of two muscle-specific E3 ubiquitin ligases, MAFbx/Atrogin-1 and Muscle RING Finger-1 (MuRF1), promoted an expectation of these molecules as targets for therapeutic development. While numerous studies have determined the conditions in which MAFbx/Atrogin-1 and MuRF1 mRNA levels are regulated, few studies have investigated their functional role in skeletal muscle. Recently, studies identifying new target substrates for MAFbx/Atrogin-1 and MuRF1, outside of their response to the initiation of muscle atrophy, suggest that there is more to these proteins than previously appreciated. This review will highlight our present knowledge of MAFbx/Atrogin-1 and MuRF1 in skeletal muscle atrophy, the impact of potential therapeutics and their known regulators and substrates. Finally, we will comment on new approaches that may expand our knowledge of these two molecules in their control of skeletal muscle function.
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the role and regulation of mafbx Atrogin 1 and murf1 in skeletal muscle atrophy
Pflügers Archiv: European Journal of Physiology, 2011Co-Authors: Victoria C Foletta, Lloyd J White, Amy E Larsen, Bertrand Leger, Aaron P RussellAbstract:Skeletal muscle atrophy occurs in many chronic diseases and disuse conditions. Its severity reduces patient recovery, independence and quality of life. The discovery of two muscle-specific E3 ubiquitin ligases, MAFbx/Atrogin-1 and Muscle RING Finger-1 (MuRF1), promoted an expectation of these molecules as targets for therapeutic development. While numerous studies have determined the conditions in which MAFbx/Atrogin-1 and MuRF1 mRNA levels are regulated, few studies have investigated their functional role in skeletal muscle. Recently, studies identifying new target substrates for MAFbx/Atrogin-1 and MuRF1, outside of their response to the initiation of muscle atrophy, suggest that there is more to these proteins than previously appreciated. This review will highlight our present knowledge of MAFbx/Atrogin-1 and MuRF1 in skeletal muscle atrophy, the impact of potential therapeutics and their known regulators and substrates. Finally, we will comment on new approaches that may expand our knowledge of these two molecules in their control of skeletal muscle function.
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Atrogin 1 murf1 and foxo as well as phosphorylated gsk 3β and 4e bp1 are reduced in skeletal muscle of chronic spinal cord injured patients
Muscle & Nerve, 2009Co-Authors: Bertrand Leger, Aaron P Russell, Charles Gobelet, Rosalba Senese, Abdul W Alkhodairy, Olivier Deriaz, Jeanpaul GiacobinoAbstract:Chronic complete spinal cord injury (SCI) is associated with severe skeletal muscle atrophy as well several atrophy and physical-inactivity-related comorbidity factors such as diabetes, obesity, lipid disorders, and cardiovascular diseases. Intracellular mechanisms associated with chronic complete SCI-related muscle atrophy are not well understood, and thus their characterization may assist with developing strategies to reduce the risk of comorbidity factors. Therefore, the aim of this study was to determine whether there was an increase in catabolic signaling targets, such as Atrogin-1, muscle ring finger-1 (MuRF1), forkhead transcription factor (FoXO), and myostatin, and decreases in anabolic signaling targets, such as insulin-like growth factor (IGF), v-akt murine thymoma viral oncogene (Akt), glycogen synthase kinase-beta (GSK-3beta), mammalian target of rapamycin (mTOR), eukaryotic initiation factor 4E binding protein 1 (4E-BP1), and p70(s6kinase) in chronic complete SCI patients. In SCI patients, when compared with controls, there was a significant reduction in mRNA levels of Atrogin-1 (59%; P < 0.05), MuRF1 (55%; P < 0.05), and myostatin (46%; P < 0.01), and in protein levels of FoXO1 (72%; P < 0.05), FoXO3a (60%; P < 0.05), and Atrogin-1 (36%; P < 0.05). Decreases in the protein levels of IGF-1 (48%; P < 0.001) and phosphorylated GSK-3beta (54%; P < 0.05), 4E-BP1 (48%; P < 0.05), and p70(s6kinase) (60%; P = 0.1) were also observed, the latter three in an Akt- and mTOR-independent manner. Reductions in Atrogin-1, MuRF1, FoXO, and myostatin suggest the existence of an internal mechanism aimed at reducing further loss of muscle proteins during chronic SCI. The downregulation of signaling proteins that regulate anabolism, such as IGF, GSK-3beta, and 4E-BP1, would reduce the ability to increase protein synthesis rates.
Kazuo Chihara - One of the best experts on this subject based on the ideXlab platform.
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branched chain amino acids reduce hindlimb suspension induced muscle atrophy and protein levels of Atrogin 1 and murf1 in rats
Nutrition Research, 2012Co-Authors: Taiki Maki, Daisuke Yamamoto, Keiji Iida, Yutaka Takahashi, Hidesuke Kaji, Kazuo Chihara, Shiho Nakanishi, Genzo Iguchi, Yasuhiko OkimuraAbstract:Atrogin-1 and MuRF1, muscle-specific ubiquitin ligases, and autophagy play a role in protein degradation in muscles. We hypothesized that branched-chain amino acids (BCAAs) may decrease Atrogin-1, MuRF1, and autophagy, and may have a protective effect on disuse muscle atrophy. To test this hypothesis, we selected hindlimb suspension (HS)–induced muscle atrophy as a model of disuse muscle atrophy because it is an established model to investigate the effects of decreased muscle activity. Sprague-Dawley male rats were assigned to 4 groups: control, HS (14 days), oral BCAA administration (600 mg/[kg day], 22.9% l-isoleucine, 45.8% l-leucine, and 27.6% l-valine), and HS and BCAA administration. After 14 days of the treatment, muscle weights and protein concentrations, cross-sectional area (CSA) of the muscle fibers, Atrogin-1 and MuRF1 proteins, and microtubule-associated protein 1 light chain 3 II/I (ratio of LC3 II/I) were measured. Hindlimb suspension significantly reduced soleus muscle weight and CSA of the muscle fibers. Branched-chain amino acid administration partly but significantly reversed the HS-induced decrease in CSA. Hindlimb suspension increased Atrogin-1 and MuRF1 proteins, which play a pivotal role in various muscle atrophies. Branched-chain amino acid attenuated the increase in Atrogin-1 and MuRF1 in soleus muscles. Hindlimb suspension significantly increased the ratio of LC3 II/I, an indicator of autophagy, whereas BCAA did not attenuate the increase in the ratio of LC3 II/I. These results indicate the possibility that BCAA inhibits HS-induced muscle atrophy, at least in part, via the inhibition of the ubiquitin-proteasome pathway. Oral BCAA administration appears to have the potential to prevent disuse muscle atrophy.
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branched chain amino acids and arginine suppress mafbx Atrogin 1 mrna expression via mtor pathway in c2c12 cell line
Biochimica et Biophysica Acta, 2008Co-Authors: Elizabeth Henny Herningtyas, Yasuhiko Okimura, Anastasia Evi Handayaningsih, Daisuke Yamamoto, Taiki Maki, Keiji Iida, Yutaka Takahashi, Hidesuke Kaji, Kazuo ChiharaAbstract:Abstract The effect of amino acid on muscle protein degradation remains unclear. Recent studies have elucidated that proteolysis in catabolic conditions occurs through ubiquitin–proteasome proteolysis pathway and that muscle-specific ubiquitin ligases (Atrogin-1 and MuRF1) play an important role in protein degradation. In the present study, we examined the direct effect of 5 mM amino acids (leucine, isoleucine, valine, glutamine and arginine) on Atrogin-1 and MuRF1 levels in C2C12 muscle cells and the involved intracellular signal transduction pathway. Leucine, isoleucine and valine suppressed Atrogin-1 and MuRF1 mRNA levels (≈ 50%) at 6 and 24 h stimulations. Arginine showed a similar effect except at 24 h-treatment for Atrogin-1 mRNA. However, glutamine failed to reduce Atrogin-1 and MuRF1 mRNA levels. The inhibitory effect of leucine, isoleucine or arginine on Atrogin-1 mRNA level was reversed by rapamycin, although wortmannin did not reverse the effect. PD98059 and HA89 reduced basal Atrogin-1 level without influencing the inhibitory effects of those amino acids. The inhibitory effect of leucine, isoleucine or arginine on MuRF1 mRNA levels was not reversed by rapamycin. Taken together, these findings indicated that leucine, isoleucine and arginine decreased Atrogin-1 mRNA levels via mTOR and that different pathways were involved in the effect of those amino acids on MuRF1 mRNA levels.
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branched chain amino acids and arginine suppress mafbx Atrogin 1 mrna expression via mtor pathway in c2c12 cell line
Biochimica et Biophysica Acta, 2008Co-Authors: Elizabeth Henny Herningtyas, Yasuhiko Okimura, Anastasia Evi Handayaningsih, Daisuke Yamamoto, Taiki Maki, Keiji Iida, Yutaka Takahashi, Hidesuke Kaji, Kazuo ChiharaAbstract:The effect of amino acid on muscle protein degradation remains unclear. Recent studies have elucidated that proteolysis in catabolic conditions occurs through ubiquitin-proteasome proteolysis pathway and that muscle-specific ubiquitin ligases (Atrogin-1 and MuRF1) play an important role in protein degradation. In the present study, we examined the direct effect of 5 mM amino acids (leucine, isoleucine, valine, glutamine and arginine) on Atrogin-1 and MuRF1 levels in C2C12 muscle cells and the involved intracellular signal transduction pathway. Leucine, isoleucine and valine suppressed Atrogin-1 and MuRF1 mRNA levels (approximately equal to 50%) at 6 and 24 h stimulations. Arginine showed a similar effect except at 24 h-treatment for Atrogin-1 mRNA. However, glutamine failed to reduce Atrogin-1 and MuRF1 mRNA levels. The inhibitory effect of leucine, isoleucine or arginine on Atrogin-1 mRNA level was reversed by rapamycin, although wortmannin did not reverse the effect. PD98059 and HA89 reduced basal Atrogin-1 level without influencing the inhibitory effects of those amino acids. The inhibitory effect of leucine, isoleucine or arginine on MuRF1 mRNA levels was not reversed by rapamycin. Taken together, these findings indicated that leucine, isoleucine and arginine decreased Atrogin-1 mRNA levels via mTOR and that different pathways were involved in the effect of those amino acids on MuRF1 mRNA levels.
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ghrp 2 a ghs r agonist directly acts on myocytes to attenuate the dexamethasone induced expressions of muscle specific ubiquitin ligases Atrogin 1 and murf1
Life Sciences, 2008Co-Authors: Daisuke Yamamoto, Elizabeth Henny Herningtyas, Keiji Iida, Yutaka Takahashi, Hidesuke Kaji, Nobuko Ikeshita, Takako Matsubara, Hiromitsu Tasaki, Keizo Toda, Kazuo ChiharaAbstract:Abstract Recent reports suggest that Atrogin-1 and MuRF1, E3 ubiquitin ligases, play a pivotal role in muscle atrophy. In the present study, effect of Growth Hormone Releasing Peptide-2 (GHRP-2), a GH secretagogue receptor (GHS-R) agonist, on the expressions of Atrogin-1 and MuRF1 in vivo rat muscles was examined. Dexamethasone administration increased Atrogin-1 mRNA level in rat soleus muscle. The increased mRNA level of Atrogin-1 was significantly attenuated by GHRP-2. In addition, GHRP-2 decreased MuRF1 mRNA level irrespective of the presence of dexamethasone. Although IGF-I is a well-known protective factor for muscle atrophy, GHRP-2 did not influence plasma IGF-I levels and IGF-I mRNA levels in muscles. To clarify a direct effect of GHRP-2, differentiated C2C12 myocytes were used. Ten micrometer dexamethasone increased both Atrogin-1 and MuRF1 mRNA levels in C2C12 cells. GHRP-2 attenuated dexamethasone-induced expression of them dose-dependently and decreased the basal level of MuRF1 mRNA. The suppressive effect on the expressions of Atrogin-1 and MuRF1 by GHRP-2 was blocked by [ d -Lys 3 ]-GHRP-6, a GHS-R1a blocker, suggesting the effect of GHRP-2 was mediated through GHS-R1a. Taken together, GHRP-2 directly attenuates Atrogin-1 and MuRF1 mRNA levels through ghrelin receptors in myocytes.
Akira Ohtsuka - One of the best experts on this subject based on the ideXlab platform.
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β1 and β2 adrenergic receptor stimulation differ in their effects on pgc 1α and Atrogin 1 mafbx gene expression in chick skeletal muscle
Comparative Biochemistry and Physiology A-molecular & Integrative Physiology, 2017Co-Authors: Saki Shimamoto, Daichi Ijiri, Kazuki Nakashima, Mana Kawaguchi, Osamu Tada, H Inoue, Akira OhtsukaAbstract:Adrenaline changes expression of the genes encoding peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α), which is known as a regulator of muscle size, and Atrogin-1/muscle atrophy F-box (MAFbx), which is a muscle-specific ubiquitin ligase. However, the subtype of β-adrenergic receptor (β-AR) involved in regulating these genes in skeletal muscle is not yet well defined. In this study, the effects of intraperitoneal injection of adrenaline and three β1-3-AR selective agonists on chick skeletal muscle metabolism were examined, to evaluate the functions of β-AR subtypes. Adrenaline decreased Atrogin-1/MAFbx mRNA levels accompanied by an increase in PGC-1α mRNA and protein levels. However, among the three selective agonists, only the β1-AR agonist, dobutamine, increased PGC-1α mRNA and protein levels, while the β2-AR agonist, clenbuterol, suppressed Atrogin-1/MAFbx mRNA levels. In addition, preinjection of the β1-AR antagonist, acebutolol, and the β2-AR antagonist, butoxamine, inhibited the adrenaline-induced increase in PGC-1α mRNA levels and the decrease in Atrogin-1/MAFbx mRNA levels, respectively. Compared with adrenaline administration, the β3-AR agonist, BRL37344, decreased PGC-1α mRNA levels and increased Atrogin-1/MAFbx mRNA levels. These results suggest that, in chick skeletal muscle, PGC-1α is induced via the β1-AR, while Atrogin-1/MAFbx is suppressed via the β2-AR.
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effects of insulin like growth factor i on the expression of Atrogin 1 mafbx in chick myotube cultures
Journal of Poultry Science, 2017Co-Authors: Kazuki Nakashima, Saki Shimamoto, Daichi Ijiri, Aiko Ishida, Akira OhtsukaAbstract:The expression of Atrogin-1/MAFbx, a muscle-specific E3 ubiquitin ligase, is increased in catabolic conditions that result in muscle atrophy. The expression of Atrogin-1/MAFbx mRNA is also decreased by the insulin-like growth factor-I (IGF-I) in mammalian skeletal muscle cell cultures. This study investigated the effect of IGF-I on the expression of Atrogin-1/MAFbx in chicken skeletal muscle cell cultures. Chick myotubes were incubated with IGF-I for 1, 6, or 24 h. Protein content was increased by IGF-I (100 ng/ml) and incubated for 24 h in chick myotubes. The expression of Atrogin-1/MAFbx mRNA decreased in the presence of IGF-I (1, 10, and 100 ng/ml) for 6 h in chick myotubes. The expression of the m-calpain large subunit and cathepsin B mRNA was not decreased by IGF-I. Phosphorylation of Akt and FOXO1 increased in the presence of IGF-I (100 ng/ml) for 1 h in chick myotubes. These results indicate that IGF-I suppresses Atrogin-1/MAFbx mRNA expression by phosphorylation of Akt and FOXO1, resulting in an increase in muscle growth in chick myotube cultures.
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Effects of first exogenous nutrients on the mRNA levels of Atrogin-1/MAFbx and GLUT1 in the skeletal muscles of newly hatched chicks Part A Molecular & integrative physiology
Comparative Biochemistry and Physiology, 2017Co-Authors: Daichi Ijiri, Saki Shimamoto, Kazuki Nakashima, Mana Kawaguchi, Airi Furukawa, Osamu Tada, Akira OhtsukaAbstract:The aim of this study was to examine the effects of first exogenous nutrients on the mRNA levels of muscle atrophy F-box (Atrogin-1/MAFbx) and glucose transporters (GLUTs) in the skeletal muscles of newly hatched chicks with no feed experience. In experiment 1, newly hatched chicks had free access to feed or were fasted for the first 24h. The chicks having free access to feed for the first 24h increased their body weight and had decreased Atrogin-1/MAFbx mRNA levels in their sartorius and pectoralis major muscles compared with the fasted chicks. In experiment 2, newly hatched chicks received a single feed via intubation into the crop. Three hours after intubation, levels of Atrogin-1/MAFbx mRNA in the sartorius muscle were decreased whereas the plasma insulin concentration and phosphorylated AKT levels in the sartorius muscle were increased. In addition, the mRNA levels of GLUT1 and GLUT8 were increased in the sartorius muscle after the intubation. However, in the pectoralis major muscle, AKT phosphorylation and levels of Atrogin-1/MAFbx, GLUT1 and GLUT8 mRNA were not affected 3h after intubation. The first exogenous nutrients increased the level of phosphorylated AKT in the sartorius muscle of newly hatched chicks, possibly because of the decrease in Atrogin-1/MAFbx mRNA levels. Furthermore, the sartorius muscle in newly hatched chicks appeared to be more susceptible to the first feed compared with the pectoralis major muscle.
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effect of dexamethasone on the expression of Atrogin 1 mafbx in chick skeletal muscle
Animal Science Journal, 2016Co-Authors: Kazuki Nakashima, Daichi Ijiri, Aiko Ishida, Akira OhtsukaAbstract:Expression of Atrogin-1/MAFbx, a muscle-specific E3 ubiquitin ligase, is high under catabolic conditions, that result in muscle atrophy. Messenger RNA (mRNA) expression of Atrogin-1/MAFbx is increased by the glucocorticoid dexamethasone in mammalian skeletal muscle. This study investigated the effects of dexamethasone on expression of Atrogin-1/MAFbx in skeletal muscle of neonatal chicks and in chick myotubes. Chicks were given a single intraperitoneal injection of dexamethasone at a concentration of 10 mg/kg body weight. Twenty-four hours after dexamethasone administration, the Pectoralis muscle weight of chicks was decreased. mRNA expression of Atrogin-1/MAFbx in skeletal muscle of chicks was significantly increased by dexamethasone administration. Expression of other proteolytic-related genes (20S proteasome C2 subunit, m-calpain large subunit, and cathepsin B) in skeletal muscle of chicks was not increased by dexamethasone administration. Chick myotubes were incubated with dexamethasone (1, 10 or 100 µmol/L) for 6 h. Expression of Atrogin-1/MAFbx mRNA in chick myotubes was increased in the presence of all concentrations of dexamethasone. However, expression of other proteolytic-related genes (20S proteasome C2 subunit, m-calpain large subunit and cathepsin B) in chick myotubes was not affected by dexamethasone treatment. These results indicate that dexamethasone enhances Atrogin-1/MAFbx expression in chick skeletal muscle, resulting in increased muscle atrophy.
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gene expression of muscle specific ubiquitin ligase Atrogin 1 mafbx positively correlates with skeletal muscle proteolysis in food deprived broiler chickens
Journal of Poultry Science, 2011Co-Authors: Akira Ohtsuka, Kazuki Nakashima, Noriko Kawatomi, Taro Araki, Kunioki HayashiAbstract:A relationship between skeletal muscle proteolysis and mRNA expression of Atrogin-1/MAFbx, a muscle-specific ubiquitin ligase, was examined in food-deprived broiler chickens. In response to food deprivation for 24 and 48h, body and muscle weights decreased in a time-dependent manner. Muscle free Nτ-methylhistidine content, an index of myofibrillar proteolysis, was 1.8-fold and 2.5-fold greater than that of fed controls following 24 and 48h of food deprivation, respectively. Gene expression of Atrogin-1/MAFbx drastically increased in response to food deprivation in a time-dependent manner. At 48h of food deprivation, the induction of Atrogin-1/MAFbx mRNA expression level elevated up to 20-fold greater than that of fed controls. By contrast, mRNA expression levels of 20S proteasome C1 and C2 subunits tended to decrease with time. No significant difference was seen in the change of ubiquitin mRNA expression. A highly significant linear negative relationship (r2=0.754, P<0.001) was found between Atrogin-1/MAFbx expression and muscle mass, while a highly significant linear positive relationship (r2=0.784, P<0.001) was found between Atrogin-1/MAFbx expression and muscle free Nτ-methylhistidine content. These results indicate that Atrogin-1/MAFbx plays a critical role in the development of muscle proteolysis and its gene expression is a reliable index of muscle proteolysis in broiler chickens.
Elizabeth Henny Herningtyas - One of the best experts on this subject based on the ideXlab platform.
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branched chain amino acids and arginine suppress mafbx Atrogin 1 mrna expression via mtor pathway in c2c12 cell line
Biochimica et Biophysica Acta, 2008Co-Authors: Elizabeth Henny Herningtyas, Yasuhiko Okimura, Anastasia Evi Handayaningsih, Daisuke Yamamoto, Taiki Maki, Keiji Iida, Yutaka Takahashi, Hidesuke Kaji, Kazuo ChiharaAbstract:Abstract The effect of amino acid on muscle protein degradation remains unclear. Recent studies have elucidated that proteolysis in catabolic conditions occurs through ubiquitin–proteasome proteolysis pathway and that muscle-specific ubiquitin ligases (Atrogin-1 and MuRF1) play an important role in protein degradation. In the present study, we examined the direct effect of 5 mM amino acids (leucine, isoleucine, valine, glutamine and arginine) on Atrogin-1 and MuRF1 levels in C2C12 muscle cells and the involved intracellular signal transduction pathway. Leucine, isoleucine and valine suppressed Atrogin-1 and MuRF1 mRNA levels (≈ 50%) at 6 and 24 h stimulations. Arginine showed a similar effect except at 24 h-treatment for Atrogin-1 mRNA. However, glutamine failed to reduce Atrogin-1 and MuRF1 mRNA levels. The inhibitory effect of leucine, isoleucine or arginine on Atrogin-1 mRNA level was reversed by rapamycin, although wortmannin did not reverse the effect. PD98059 and HA89 reduced basal Atrogin-1 level without influencing the inhibitory effects of those amino acids. The inhibitory effect of leucine, isoleucine or arginine on MuRF1 mRNA levels was not reversed by rapamycin. Taken together, these findings indicated that leucine, isoleucine and arginine decreased Atrogin-1 mRNA levels via mTOR and that different pathways were involved in the effect of those amino acids on MuRF1 mRNA levels.
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branched chain amino acids and arginine suppress mafbx Atrogin 1 mrna expression via mtor pathway in c2c12 cell line
Biochimica et Biophysica Acta, 2008Co-Authors: Elizabeth Henny Herningtyas, Yasuhiko Okimura, Anastasia Evi Handayaningsih, Daisuke Yamamoto, Taiki Maki, Keiji Iida, Yutaka Takahashi, Hidesuke Kaji, Kazuo ChiharaAbstract:The effect of amino acid on muscle protein degradation remains unclear. Recent studies have elucidated that proteolysis in catabolic conditions occurs through ubiquitin-proteasome proteolysis pathway and that muscle-specific ubiquitin ligases (Atrogin-1 and MuRF1) play an important role in protein degradation. In the present study, we examined the direct effect of 5 mM amino acids (leucine, isoleucine, valine, glutamine and arginine) on Atrogin-1 and MuRF1 levels in C2C12 muscle cells and the involved intracellular signal transduction pathway. Leucine, isoleucine and valine suppressed Atrogin-1 and MuRF1 mRNA levels (approximately equal to 50%) at 6 and 24 h stimulations. Arginine showed a similar effect except at 24 h-treatment for Atrogin-1 mRNA. However, glutamine failed to reduce Atrogin-1 and MuRF1 mRNA levels. The inhibitory effect of leucine, isoleucine or arginine on Atrogin-1 mRNA level was reversed by rapamycin, although wortmannin did not reverse the effect. PD98059 and HA89 reduced basal Atrogin-1 level without influencing the inhibitory effects of those amino acids. The inhibitory effect of leucine, isoleucine or arginine on MuRF1 mRNA levels was not reversed by rapamycin. Taken together, these findings indicated that leucine, isoleucine and arginine decreased Atrogin-1 mRNA levels via mTOR and that different pathways were involved in the effect of those amino acids on MuRF1 mRNA levels.
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ghrp 2 a ghs r agonist directly acts on myocytes to attenuate the dexamethasone induced expressions of muscle specific ubiquitin ligases Atrogin 1 and murf1
Life Sciences, 2008Co-Authors: Daisuke Yamamoto, Elizabeth Henny Herningtyas, Keiji Iida, Yutaka Takahashi, Hidesuke Kaji, Nobuko Ikeshita, Takako Matsubara, Hiromitsu Tasaki, Keizo Toda, Kazuo ChiharaAbstract:Abstract Recent reports suggest that Atrogin-1 and MuRF1, E3 ubiquitin ligases, play a pivotal role in muscle atrophy. In the present study, effect of Growth Hormone Releasing Peptide-2 (GHRP-2), a GH secretagogue receptor (GHS-R) agonist, on the expressions of Atrogin-1 and MuRF1 in vivo rat muscles was examined. Dexamethasone administration increased Atrogin-1 mRNA level in rat soleus muscle. The increased mRNA level of Atrogin-1 was significantly attenuated by GHRP-2. In addition, GHRP-2 decreased MuRF1 mRNA level irrespective of the presence of dexamethasone. Although IGF-I is a well-known protective factor for muscle atrophy, GHRP-2 did not influence plasma IGF-I levels and IGF-I mRNA levels in muscles. To clarify a direct effect of GHRP-2, differentiated C2C12 myocytes were used. Ten micrometer dexamethasone increased both Atrogin-1 and MuRF1 mRNA levels in C2C12 cells. GHRP-2 attenuated dexamethasone-induced expression of them dose-dependently and decreased the basal level of MuRF1 mRNA. The suppressive effect on the expressions of Atrogin-1 and MuRF1 by GHRP-2 was blocked by [ d -Lys 3 ]-GHRP-6, a GHS-R1a blocker, suggesting the effect of GHRP-2 was mediated through GHS-R1a. Taken together, GHRP-2 directly attenuates Atrogin-1 and MuRF1 mRNA levels through ghrelin receptors in myocytes.
Yasuhiko Okimura - One of the best experts on this subject based on the ideXlab platform.
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branched chain amino acids reduce hindlimb suspension induced muscle atrophy and protein levels of Atrogin 1 and murf1 in rats
Nutrition Research, 2012Co-Authors: Taiki Maki, Daisuke Yamamoto, Keiji Iida, Yutaka Takahashi, Hidesuke Kaji, Kazuo Chihara, Shiho Nakanishi, Genzo Iguchi, Yasuhiko OkimuraAbstract:Atrogin-1 and MuRF1, muscle-specific ubiquitin ligases, and autophagy play a role in protein degradation in muscles. We hypothesized that branched-chain amino acids (BCAAs) may decrease Atrogin-1, MuRF1, and autophagy, and may have a protective effect on disuse muscle atrophy. To test this hypothesis, we selected hindlimb suspension (HS)–induced muscle atrophy as a model of disuse muscle atrophy because it is an established model to investigate the effects of decreased muscle activity. Sprague-Dawley male rats were assigned to 4 groups: control, HS (14 days), oral BCAA administration (600 mg/[kg day], 22.9% l-isoleucine, 45.8% l-leucine, and 27.6% l-valine), and HS and BCAA administration. After 14 days of the treatment, muscle weights and protein concentrations, cross-sectional area (CSA) of the muscle fibers, Atrogin-1 and MuRF1 proteins, and microtubule-associated protein 1 light chain 3 II/I (ratio of LC3 II/I) were measured. Hindlimb suspension significantly reduced soleus muscle weight and CSA of the muscle fibers. Branched-chain amino acid administration partly but significantly reversed the HS-induced decrease in CSA. Hindlimb suspension increased Atrogin-1 and MuRF1 proteins, which play a pivotal role in various muscle atrophies. Branched-chain amino acid attenuated the increase in Atrogin-1 and MuRF1 in soleus muscles. Hindlimb suspension significantly increased the ratio of LC3 II/I, an indicator of autophagy, whereas BCAA did not attenuate the increase in the ratio of LC3 II/I. These results indicate the possibility that BCAA inhibits HS-induced muscle atrophy, at least in part, via the inhibition of the ubiquitin-proteasome pathway. Oral BCAA administration appears to have the potential to prevent disuse muscle atrophy.
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branched chain amino acids and arginine suppress mafbx Atrogin 1 mrna expression via mtor pathway in c2c12 cell line
Biochimica et Biophysica Acta, 2008Co-Authors: Elizabeth Henny Herningtyas, Yasuhiko Okimura, Anastasia Evi Handayaningsih, Daisuke Yamamoto, Taiki Maki, Keiji Iida, Yutaka Takahashi, Hidesuke Kaji, Kazuo ChiharaAbstract:Abstract The effect of amino acid on muscle protein degradation remains unclear. Recent studies have elucidated that proteolysis in catabolic conditions occurs through ubiquitin–proteasome proteolysis pathway and that muscle-specific ubiquitin ligases (Atrogin-1 and MuRF1) play an important role in protein degradation. In the present study, we examined the direct effect of 5 mM amino acids (leucine, isoleucine, valine, glutamine and arginine) on Atrogin-1 and MuRF1 levels in C2C12 muscle cells and the involved intracellular signal transduction pathway. Leucine, isoleucine and valine suppressed Atrogin-1 and MuRF1 mRNA levels (≈ 50%) at 6 and 24 h stimulations. Arginine showed a similar effect except at 24 h-treatment for Atrogin-1 mRNA. However, glutamine failed to reduce Atrogin-1 and MuRF1 mRNA levels. The inhibitory effect of leucine, isoleucine or arginine on Atrogin-1 mRNA level was reversed by rapamycin, although wortmannin did not reverse the effect. PD98059 and HA89 reduced basal Atrogin-1 level without influencing the inhibitory effects of those amino acids. The inhibitory effect of leucine, isoleucine or arginine on MuRF1 mRNA levels was not reversed by rapamycin. Taken together, these findings indicated that leucine, isoleucine and arginine decreased Atrogin-1 mRNA levels via mTOR and that different pathways were involved in the effect of those amino acids on MuRF1 mRNA levels.
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branched chain amino acids and arginine suppress mafbx Atrogin 1 mrna expression via mtor pathway in c2c12 cell line
Biochimica et Biophysica Acta, 2008Co-Authors: Elizabeth Henny Herningtyas, Yasuhiko Okimura, Anastasia Evi Handayaningsih, Daisuke Yamamoto, Taiki Maki, Keiji Iida, Yutaka Takahashi, Hidesuke Kaji, Kazuo ChiharaAbstract:The effect of amino acid on muscle protein degradation remains unclear. Recent studies have elucidated that proteolysis in catabolic conditions occurs through ubiquitin-proteasome proteolysis pathway and that muscle-specific ubiquitin ligases (Atrogin-1 and MuRF1) play an important role in protein degradation. In the present study, we examined the direct effect of 5 mM amino acids (leucine, isoleucine, valine, glutamine and arginine) on Atrogin-1 and MuRF1 levels in C2C12 muscle cells and the involved intracellular signal transduction pathway. Leucine, isoleucine and valine suppressed Atrogin-1 and MuRF1 mRNA levels (approximately equal to 50%) at 6 and 24 h stimulations. Arginine showed a similar effect except at 24 h-treatment for Atrogin-1 mRNA. However, glutamine failed to reduce Atrogin-1 and MuRF1 mRNA levels. The inhibitory effect of leucine, isoleucine or arginine on Atrogin-1 mRNA level was reversed by rapamycin, although wortmannin did not reverse the effect. PD98059 and HA89 reduced basal Atrogin-1 level without influencing the inhibitory effects of those amino acids. The inhibitory effect of leucine, isoleucine or arginine on MuRF1 mRNA levels was not reversed by rapamycin. Taken together, these findings indicated that leucine, isoleucine and arginine decreased Atrogin-1 mRNA levels via mTOR and that different pathways were involved in the effect of those amino acids on MuRF1 mRNA levels.