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Article ; Online: Insight into the Role of Gut Microbiota in Duchenne Muscular Dystrophy: An Age-Related Study in Mdx Mice.

Jollet, Maxence / Mariadassou, Mahendra / Rué, Olivier / Pessemesse, Laurence / Ollendorff, Vincent / Ramdani, Sofiane / Vernus, Barbara / Bonnieu, Anne / Bertrand-Gaday, Christelle / Goustard, Bénédicte / Koechlin-Ramonatxo, Christelle

The American journal of pathology

2023 Volume 194, Issue 2, Page(s) 264–279

Abstract: Dystrophin deficiency alters the sarcolemma structure, leading to muscle dystrophy, muscle disuse, and ultimately death. Beyond limb muscle deficits, patients with Duchenne muscular dystrophy have numerous transit disorders. Many studies have highlighted ...

Abstract	Dystrophin deficiency alters the sarcolemma structure, leading to muscle dystrophy, muscle disuse, and ultimately death. Beyond limb muscle deficits, patients with Duchenne muscular dystrophy have numerous transit disorders. Many studies have highlighted the strong relationship between gut microbiota and skeletal muscle. The aims of this study were: i) to characterize the gut microbiota composition over time up to 1 year in dystrophin-deficient mdx mice, and ii) to analyze the intestine structure and function and expression of genes linked to bacterial-derived metabolites in ileum, blood, and skeletal muscles to study interorgan interactions. Mdx mice displayed a significant reduction in the overall number of different operational taxonomic units and their abundance (α-diversity). Mdx genotype predicted 20% of β-diversity divergence, with a large taxonomic modification of Actinobacteria, Proteobacteria, Tenericutes, and Deferribacteres phyla and the included genera. Interestingly, mdx intestinal motility and gene expressions of tight junction and Ffar2 receptor were down-regulated in the ileum. Concomitantly, circulating inflammatory markers related to gut microbiota (tumor necrosis factor, IL-6, monocyte chemoattractant protein-1) and muscle inflammation Tlr4/Myd88 pathway (Toll-like receptor 4, which recognizes pathogen-associated molecular patterns) were up-regulated. Finally, in mdx mice, adiponectin was reduced in blood and its receptor modulated in muscles. This study highlights a specific gut microbiota composition and highlights interorgan interactions in mdx physiopathology with gut microbiota as the potential central metabolic organ.
MeSH term(s)	Animals ; Humans ; Mice ; Dystrophin/deficiency ; Dystrophin/genetics ; Gastrointestinal Microbiome ; Mice, Inbred mdx ; Muscle, Skeletal/metabolism ; Muscular Dystrophy, Duchenne/genetics ; Muscular Dystrophy, Duchenne/pathology
Chemical Substances	Dystrophin
Language	English
Publishing date	2023-11-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2943-9
ISSN	1525-2191 ; 0002-9440
ISSN (online)	1525-2191
ISSN	0002-9440
DOI	10.1016/j.ajpath.2023.10.010
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Article: Myostatin gene inactivation increases post-mortem calpain-dependent muscle proteolysis in mice

Nassar, Rim / Vernus, Barbara / Carnac, Gilles / Fouret, Gilles / Goustard, Bénédicte / Casas, François / Tintignac, Lionel / Cassar-Malek, Isabelle / Picard, Brigitte / Seiliez, Iban / Brioche, Thomas / Koechlin-Ramonatxo, Christelle / Bertrand-Gaday, Christelle / Hamade, Aline / Najjar, Fadia / Chabi, Béatrice / Bonnieu, Anne

Meat science. 2022 Mar., v. 185

2022

Abstract: Myostatin deficiency leads to extensive skeletal muscle hypertrophy, but its consequence on post-mortem muscle proteolysis is unknown. Here, we compared muscle myofibrillar protein degradation, and autophagy, ubiquitin-proteasome and Ca²⁺-dependent ... ...

Abstract	Myostatin deficiency leads to extensive skeletal muscle hypertrophy, but its consequence on post-mortem muscle proteolysis is unknown. Here, we compared muscle myofibrillar protein degradation, and autophagy, ubiquitin-proteasome and Ca²⁺-dependent proteolysis relative to the energetic and redox status in wild-type (WT) and myostatin knock-out mice (KO) during early post-mortem storage. KO muscles showed higher degradation of myofibrillar proteins in the first 24 h after death, associated with preserved antioxidant status, compared with WT muscles. Analysis of key autophagy and ubiquitin-proteasome system markers indicated that these two pathways were not upregulated in post-mortem muscle (both genotypes), but basal autophagic flux and ATP content were lower in KO muscles. Proteasome and caspase activities were not different between WT and KO mice. Conversely, calpain activity was higher in KO muscles, concomitantly with higher troponin T and desmin degradation. Altogether, these results suggest that calpains but not the autophagy, proteasome and caspase systems, explain the difference in post-mortem muscle protein proteolysis between both genotypes.
Keywords	antioxidants ; autophagy ; calpain ; caspases ; death ; desmin ; gene silencing ; hypertrophy ; meat science ; muscle protein ; muscles ; myostatin ; proteasome endopeptidase complex ; protein degradation ; proteolysis ; skeletal muscle ; troponin T
Language	English
Dates of publication	2022-03
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	753319-6
ISSN	1873-4138 ; 0309-1740
ISSN (online)	1873-4138
ISSN	0309-1740
DOI	10.1016/j.meatsci.2021.108726
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Article ; Online: Transient Changes of Metabolism at the Pronuclear Stage in Mice Influences Skeletal Muscle Phenotype in Adulthood.

Bertrand-Gaday, Christelle / Letheule, Martine / Blanchet, Emilie / Vernus, Barbara / Pessemesse, Laurence / Bonnet-Garnier, Amélie / Bonnieu, Anne / Casas, François

International journal of molecular sciences

2020 Volume 21, Issue 19

Abstract: Skeletal muscle has a remarkable plasticity, and its phenotype is strongly influenced by hormones, transcription factors, and physical activity. However, whether skeletal phenotype can be oriented or not during early embryonic stages has never been ... ...

Abstract	Skeletal muscle has a remarkable plasticity, and its phenotype is strongly influenced by hormones, transcription factors, and physical activity. However, whether skeletal phenotype can be oriented or not during early embryonic stages has never been investigated. Here, we report that pyruvate as the only source of carbohydrate in the culture medium of mouse one cell stage embryo influenced the establishment of the muscular phenotype in adulthood. We found that pyruvate alone induced changes in the contractile phenotype of the skeletal muscle in a sexually dependent manner. For male mice, a switch to a more glycolytic phenotype was recorded, whereas, in females, the pyruvate induced a switch to a more oxidative phenotype. In addition, the influence of pyruvate on the contractile phenotypes was confirmed in two mouse models of muscle hypertrophy: the well-known myostatin deficient mouse (Mstn-/-) and a mouse carrying a specific deletion of p43, a mitochondrial triiodothyronine receptor. Finally, to understand the link between these adult phenotypes and the early embryonic period, we assessed the levels of two histone H3 post-translational modifications in presence of pyruvate alone just after the wave of chromatin reprogramming specific of the first cell cycle. We showed that H3K4 acetylation level was decreased in Mstn-/- 2-cell embryos, whereas no difference was found for H3K27 trimethylation level, whatever the genotype. These findings demonstrate for the first time that changes in the access of energy substrate during the very first embryonic stage can induce a precocious orientation of skeletal muscle phenotype in adulthood.
MeSH term(s)	Acetylation ; Animals ; Carbohydrate Metabolism/genetics ; Cytokines/genetics ; Disease Models, Animal ; Embryo, Mammalian ; Embryonic Development/genetics ; Female ; Genotype ; Glycolysis/genetics ; Hypertrophy/genetics ; Hypertrophy/metabolism ; Hypertrophy/pathology ; Male ; Mice ; Mitochondria/metabolism ; Muscle Contraction/genetics ; Muscle, Skeletal/metabolism ; Muscle, Skeletal/pathology ; Myostatin/genetics ; Oxidation-Reduction ; Phenotype ; Pyruvic Acid/metabolism
Chemical Substances	Aimp1 protein, mouse ; Cytokines ; Mstn protein, mouse ; Myostatin ; Pyruvic Acid (8558G7RUTR)
Language	English
Publishing date	2020-09-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21197203
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Article ; Online: Does Physical Inactivity Induce Significant Changes in Human Gut Microbiota? New Answers Using the Dry Immersion Hypoactivity Model.

Jollet, Maxence / Nay, Kevin / Chopard, Angèle / Bareille, Marie-Pierre / Beck, Arnaud / Ollendorff, Vincent / Vernus, Barbara / Bonnieu, Anne / Mariadassou, Mahendra / Rué, Olivier / Derbré, Frédéric / Goustard, Bénédicte / Koechlin-Ramonatxo, Christelle

Nutrients

2021 Volume 13, Issue 11

Abstract: Gut microbiota, a major contributor to human health, is influenced by physical activity and diet, and displays a functional cross-talk with skeletal muscle. Conversely, few data are available on the impact of hypoactivity, although sedentary lifestyles ... ...

Abstract	Gut microbiota, a major contributor to human health, is influenced by physical activity and diet, and displays a functional cross-talk with skeletal muscle. Conversely, few data are available on the impact of hypoactivity, although sedentary lifestyles are widespread and associated with negative health and socio-economic impacts. The study aim was to determine the effect of Dry Immersion (DI), a severe hypoactivity model, on the human gut microbiota composition. Stool samples were collected from 14 healthy men before and after 5 days of DI to determine the gut microbiota taxonomic profiles by 16S metagenomic sequencing in strictly controlled dietary conditions. The α and β diversities indices were unchanged. However, the operational taxonomic units associated with the Clostridiales order and the
MeSH term(s)	Adult ; Feces/chemistry ; Feces/microbiology ; Gastrointestinal Microbiome/physiology ; Healthy Volunteers ; Humans ; Immersion/physiopathology ; Male ; Propionates/metabolism ; Rest/physiology ; Sedentary Behavior ; Weightlessness Simulation
Chemical Substances	Propionates
Language	English
Publishing date	2021-10-29
Publishing country	Switzerland
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu13113865
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Article: Does Physical Inactivity Induce Significant Changes in Human Gut Microbiota? New Answers Using the Dry Immersion Hypoactivity Model

Nutrients. 2021 Oct. 29, v. 13, no. 11

2021

Abstract	Gut microbiota, a major contributor to human health, is influenced by physical activity and diet, and displays a functional cross-talk with skeletal muscle. Conversely, few data are available on the impact of hypoactivity, although sedentary lifestyles are widespread and associated with negative health and socio-economic impacts. The study aim was to determine the effect of Dry Immersion (DI), a severe hypoactivity model, on the human gut microbiota composition. Stool samples were collected from 14 healthy men before and after 5 days of DI to determine the gut microbiota taxonomic profiles by 16S metagenomic sequencing in strictly controlled dietary conditions. The α and β diversities indices were unchanged. However, the operational taxonomic units associated with the Clostridiales order and the Lachnospiraceae family, belonging to the Firmicutes phylum, were significantly increased after DI. Propionate, a short-chain fatty acid metabolized by skeletal muscle, was significantly reduced in post-DI stool samples. The finding that intestine bacteria are sensitive to hypoactivity raises questions about their impact and role in chronic sedentary lifestyles.
Keywords	Lachnospiraceae ; diet ; human health ; humans ; intestinal microorganisms ; intestines ; metagenomics ; models ; physical activity ; propionic acid ; short chain fatty acids ; skeletal muscle
Language	English
Dates of publication	2021-1029
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2518386-2
ISSN	2072-6643
ISSN	2072-6643
DOI	10.3390/nu13113865
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Article: New evidence of exercise training benefits in myostatin-deficient mice: Effect on lipidomic abnormalities

Baati, Narjes / Bertrand-Gaday, Christelle / Bonnieu, Anne / Coudray, Charles / Feillet-Coudray, Christine / Fouret, Gilles / Goustard, Bénédicte / Jollet, Maxence / Koechlin-Ramonatxo, Christelle / Lecomte, Jérôme / Vernus, Barbara

Biochemical and biophysical research communications. 2019 Aug. 13, v. 516, no. 1

2019

Abstract: Myostatin (Mstn) inactivation or inhibition is considered as a promising treatment for various muscle-wasting disorders because it promotes muscle growth. However, myostatin-deficient hypertrophic muscles show strong fatigability associated with abnormal ...

Abstract	Myostatin (Mstn) inactivation or inhibition is considered as a promising treatment for various muscle-wasting disorders because it promotes muscle growth. However, myostatin-deficient hypertrophic muscles show strong fatigability associated with abnormal mitochondria and lipid metabolism. Here, we investigated whether endurance training could improve lipid metabolism and mitochondrial membrane lipid composition in mice where the Mstn gene was genetically ablated (Mstn−/- mice). In Mstn−/- mice, 4 weeks of daily running exercise sessions (65–70% of the maximal aerobic speed for 1 h) improved significantly aerobic performance, particularly the endurance capacity (up to +280% compared with untrained Mstn−/- mice), to levels comparable to those of trained wild type (WT) littermates. The expression of oxidative and lipid metabolism markers also was increased, as indicated by the upregulation of the Cpt1, Ppar-δ and Fasn genes. Moreover, endurance training also increased, but far less than WT, citrate synthase level and mitochondrial protein content. Interestingly endurance training normalized the cardiolipin fraction in the mitochondrial membrane of Mstn−/- muscle compared with WT. These results suggest that the combination of myostatin inhibition and endurance training could increase the muscle mass while preserving the physical performance with specific effects on cardiolipin and lipid-related pathways.
Keywords	cardiolipins ; citrate (si)-synthase ; exercise ; gene expression regulation ; genes ; lipid composition ; lipid metabolism ; mice ; mitochondria ; mitochondrial membrane ; muscle tissues ; muscles ; muscular atrophy ; myostatin ; protein content
Language	English
Dates of publication	2019-0813
Size	p. 89-95.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	205723-2
ISSN	0006-291X ; 0006-291X
ISSN (online)	0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2019.06.014
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Article ; Online: Myostatin deficiency is associated with an increase in number of total axons and motor axons innervating mouse tibialis anterior muscle.

Gay, Stephanie / Jublanc, Elodie / Bonnieu, Anne / Bacou, Francis

Muscle & nerve

2012 Volume 45, Issue 5, Page(s) 698–704

Abstract: Introduction: Myostatin (Mstn) is a secreted protein that acts as a negative regulator of skeletal muscle mass. However, a critical evaluation of neuromuscular aspects of hypertrophied muscles induced by Mstn deficiency has not been done.: Methods: ... ...

Abstract	Introduction: Myostatin (Mstn) is a secreted protein that acts as a negative regulator of skeletal muscle mass. However, a critical evaluation of neuromuscular aspects of hypertrophied muscles induced by Mstn deficiency has not been done. Methods: We compared the tibialis anterior muscle-nerve interrelationships in wild-type and Mstn-null mice of both genders by immunohistochemical analyses, which allowed us to count the number of total axons and motor axons and estimate the size of motor units and the innervation ratio of the tibialis anterior muscle (TAm). Results: There was an increase in the number of total axons and motor axons, and higher values in both the motor unit size and the innervation ratio of Mstn-null TAm compared with those of wild-type TAm. Conclusions: We found that myostatin is involved either directly in the control of neuromuscular interrelationships or indirectly through its effect on muscle size.
MeSH term(s)	Animals ; Axons/physiology ; Choline O-Acetyltransferase/metabolism ; Female ; Gene Expression Regulation/genetics ; Male ; Mice ; Mice, Transgenic ; Muscle Fibers, Skeletal/metabolism ; Muscle Fibers, Skeletal/pathology ; Muscle, Skeletal/innervation ; Muscle, Skeletal/pathology ; Muscle, Skeletal/physiology ; Muscular Atrophy/genetics ; Muscular Atrophy/metabolism ; Muscular Atrophy/pathology ; Myostatin/deficiency ; Neurofilament Proteins/metabolism ; Sex Factors
Chemical Substances	Mstn protein, mouse ; Myostatin ; Neurofilament Proteins ; neurofilament protein H (108688-71-7) ; Choline O-Acetyltransferase (EC 2.3.1.6)
Language	English
Publishing date	2012-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	438353-9
ISSN	1097-4598 ; 0148-639X
ISSN (online)	1097-4598
ISSN	0148-639X
DOI	10.1002/mus.23242
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Article ; Online: Acute and chronic effects of Rhaponticum carthamoides and Rhodiola rosea extracts supplementation coupled to resistance exercise on muscle protein synthesis and mechanical power in rats.

Roumanille, Rémi / Vernus, Barbara / Brioche, Thomas / Descossy, Vincent / Van Ba, Christophe Tran / Campredon, Sarah / Philippe, Antony G / Delobel, Pierre / Bertrand-Gaday, Christelle / Chopard, Angèle / Bonnieu, Anne / Py, Guillaume / Fança-Berthon, Pascale

Journal of the International Society of Sports Nutrition

2020 Volume 17, Issue 1, Page(s) 58

Abstract: Background: Owing to its strength-building and adaptogenic properties, Rhaponticum carthamoides (Rha) has been commonly used by elite Soviet and Russian athletes. Rhodiola rosea (Rho) is known to reduce physical and mental fatigue and improve endurance ... ...

Abstract	Background: Owing to its strength-building and adaptogenic properties, Rhaponticum carthamoides (Rha) has been commonly used by elite Soviet and Russian athletes. Rhodiola rosea (Rho) is known to reduce physical and mental fatigue and improve endurance performance. However, the association of these two nutritional supplements with resistance exercise performance has never been tested. Resistance exercise is still the best way to stimulate protein synthesis and induce chronic muscle adaptations. The aim of this study was to investigate the acute and chronic effects of resistance exercise coupled with Rha and Rho supplementation on protein synthesis, muscle phenotype, and physical performance. Methods: For the acute study, fifty-six rats were assigned to either a trained control group or one of the groups treated with specific doses of Rha and/or Rho. Each rats performed a single bout of climbing resistance exercise. The supplements were administered immediately after exercise by oral gavage. Protein synthesis was measured via puromycin incorporation. For the chronic study, forty rats were assigned to either the control group or one of the groups treated with doses adjusted from the acute study results. The rats were trained five times per week for 4 weeks with the same bout of climbing resistance exercise with additionals loads. Rha + Rho supplement was administered immediately after each training by oral gavage. Results: The findings of the acute study indicated that Rha and Rha + Rho supplementation after resistance exercise stimulated protein synthesis more than resistance exercise alone (p < 0.05). After 4 weeks of training, the mean power performance was increased in the Rha + Rho and Rha-alone groups (p < 0.05) without any significant supplementation effect on muscle weight or fiber cross-sectional area. A tendency towards an increase in type I/ type II fiber ratio was observed in Rha/Rho-treated groups compared to that in the trained control group. Conclusion: Rhodiola and Rhaponticum supplementation after resistance exercise could synergistically improve protein synthesis, muscle phenotype and physical performance.
MeSH term(s)	Animals ; Leuzea/chemistry ; Muscle Proteins/biosynthesis ; Muscle, Skeletal/anatomy & histology ; Muscle, Skeletal/drug effects ; Muscle, Skeletal/metabolism ; Organ Size ; Physical Functional Performance ; Plant Extracts/pharmacology ; Puromycin/metabolism ; Rats ; Rats, Wistar ; Resistance Training ; Rhodiola/chemistry
Chemical Substances	Muscle Proteins ; Plant Extracts ; Puromycin (4A6ZS6Q2CL)
Language	English
Publishing date	2020-11-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	2162810-5
ISSN	1550-2783 ; 1550-2783
ISSN (online)	1550-2783
ISSN	1550-2783
DOI	10.1186/s12970-020-00390-5
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Article ; Online: Autophagy in farm animals: current knowledge and future challenges.

Tesseraud, Sophie / Avril, Pascale / Bonnet, Muriel / Bonnieu, Anne / Cassar-Malek, Isabelle / Chabi, Béatrice / Dessauge, Frédéric / Gabillard, Jean-Charles / Perruchot, Marie-Hélène / Seiliez, Iban

Autophagy

2020 Volume 17, Issue 8, Page(s) 1809–1827

Abstract: Autophagy (a process of cellular self-eating) is a conserved cellular degradative process that plays important roles in maintaining homeostasis and preventing nutritional, metabolic, and infection-mediated stresses. Surprisingly, little attention has ... ...

Abstract	Autophagy (a process of cellular self-eating) is a conserved cellular degradative process that plays important roles in maintaining homeostasis and preventing nutritional, metabolic, and infection-mediated stresses. Surprisingly, little attention has been paid to the role of this cellular function in species of agronomical interest, and the details of how autophagy functions in the development of phenotypes of agricultural interest remain largely unexplored. Here, we first provide a brief description of the main mechanisms involved in autophagy, then review our current knowledge regarding autophagy in species of agronomical interest, with particular attention to physiological functions supporting livestock animal production, and finally assess the potential of translating the acquired knowledge to improve animal development, growth and health in the context of growing social, economic and environmental challenges for agriculture.
MeSH term(s)	AMP-Activated Protein Kinases/metabolism ; Animals ; Apoptosis Regulatory Proteins/metabolism ; Autophagy/physiology ; Farms ; Humans ; Lysosomes/metabolism ; Signal Transduction/physiology
Chemical Substances	Apoptosis Regulatory Proteins ; AMP-Activated Protein Kinases (EC 2.7.11.31)
Language	English
Publishing date	2020-07-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2454135-7
ISSN	1554-8635 ; 1554-8627
ISSN (online)	1554-8635
ISSN	1554-8627
DOI	10.1080/15548627.2020.1798064
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Article ; Online: Myostatin gene inactivation increases post-mortem calpain-dependent muscle proteolysis in mice.

Meat science

2021 Volume 185, Page(s) 108726

Abstract	Myostatin deficiency leads to extensive skeletal muscle hypertrophy, but its consequence on post-mortem muscle proteolysis is unknown. Here, we compared muscle myofibrillar protein degradation, and autophagy, ubiquitin-proteasome and Ca
MeSH term(s)	Animals ; Calpain/genetics ; Calpain/metabolism ; Gene Silencing ; Mice ; Muscle, Skeletal/metabolism ; Myostatin/genetics ; Proteolysis
Chemical Substances	Mstn protein, mouse ; Myostatin ; Calpain (EC 3.4.22.-)
Language	English
Publishing date	2021-12-24
Publishing country	England
Document type	Journal Article
ZDB-ID	753319-6
ISSN	1873-4138 ; 0309-1740
ISSN (online)	1873-4138
ISSN	0309-1740
DOI	10.1016/j.meatsci.2021.108726
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