There is increasing pressure on meat producers worldwide due to the need for higher yields and improved meat quality. This is why anabolic androgenic steroids (AAS) have been widely used in most countries, due to their ability to accelerate animal muscle growth. However, out of concern for their side effects, EU states have banned their use and implemented control mechanisms. But they are reaching their limits, and therefore, it is necessary to look for new ways and investigate the mechanism of action of AAS on muscle tissue. This study replicated the administration of banned AAS (testosterone, nandrolone and their combination) and observed their effect on pig muscle. The pig model was purposely chosen for the study, as no such research has been carried out on this species. At the same time, pork is one of the most consumed meats in Europe. It focused on histological changes in muscle structure, specifically the size of muscle fibres and the number of satellite cells per muscle fibre. Furthermore, ultrastructural changes in muscle fibres, the diameter of myofibrils, the number of myofibrils per area, the distance between myofibrils and the size of sarcomeres were examined. The results using the techniques of histology, fluorescent labelling and transmission electron microscopy showed that, after the application of AAS, there is an increase in the diameter of muscle fibres, an increase in the diameter of myofibrils, a decrease in the number of myofibrils per surface area and, in the case of testosterone, an increase in the distance between myofibrils and an increase in the length of sarcomeres. There was also a significant increase in the number of satellite cells per muscle fibre. The detected statistically significant differences between control and experimental groups provide evidence that selected histological parameters could be additional mechanisms for detecting the presence of AAS in pork meat in the future.
- MeSH
- Anabolic Agents * pharmacology MeSH
- Muscle Fibers, Skeletal * drug effects ultrastructure MeSH
- Muscle, Skeletal drug effects anatomy & histology ultrastructure MeSH
- Myofibrils * drug effects ultrastructure MeSH
- Nandrolone * pharmacology MeSH
- Swine anatomy & histology MeSH
- Sarcomeres drug effects ultrastructure MeSH
- Satellite Cells, Skeletal Muscle drug effects ultrastructure MeSH
- Testosterone * pharmacology MeSH
- Microscopy, Electron, Transmission veterinary MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Hypertrophic cardiomyopathy (HCM) caused by autosomal-dominant mutations in genes coding for structural sarcomeric proteins, is the most common inherited heart disease. HCM is associated with myocardial hypertrophy, fibrosis and ventricular dysfunction. Hypoxia-inducible transcription factor-1α (Hif-1α) is the central master regulators of cellular hypoxia response and associated with HCM. Yet its exact role remains to be elucidated. Therefore, the effect of a cardiomyocyte-specific Hif-1a knockout (cHif1aKO) was studied in an established α-MHC719/+ HCM mouse model that exhibits the classical features of human HCM. The results show that Hif-1α protein and HIF targets were upregulated in left ventricular tissue of α-MHC719/+ mice. Cardiomyocyte-specific abolishment of Hif-1a blunted the disease phenotype, as evidenced by decreased left ventricular wall thickness, reduced myocardial fibrosis, disordered SRX/DRX state and ROS production. cHif1aKO induced normalization of pro-hypertrophic and pro-fibrotic left ventricular remodeling signaling evidenced on whole transcriptome and proteomics analysis in α-MHC719/+ mice. Proteomics of serum samples from patients with early onset HCM revealed significant modulation of HIF. These results demonstrate that HIF signaling is involved in mouse and human HCM pathogenesis. Cardiomyocyte-specific knockout of Hif-1a attenuates disease phenotype in the mouse model. Targeting Hif-1α might serve as a therapeutic option to mitigate HCM disease progression.
- MeSH
- Hypoxia-Inducible Factor 1, alpha Subunit * metabolism genetics MeSH
- Fibrosis MeSH
- Cardiomyopathy, Hypertrophic * metabolism genetics pathology MeSH
- Myocytes, Cardiac * metabolism pathology MeSH
- Humans MeSH
- Disease Models, Animal * MeSH
- Mice, Knockout * MeSH
- Mice MeSH
- Sarcomeres * metabolism MeSH
- Signal Transduction MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- Cardiomyopathy, Hypertrophic * genetics diagnosis MeSH
- Humans MeSH
- Mutation * MeSH
- Predictive Value of Tests MeSH
- Sarcomeres * genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Letter MeSH
- Editorial MeSH
Formation of oriented myofibrils is a key event in musculoskeletal development. However, the mechanisms that drive myocyte orientation and fusion to control muscle directionality in adults remain enigmatic. Here, we demonstrate that the developing skeleton instructs the directional outgrowth of skeletal muscle and other soft tissues during limb and facial morphogenesis in zebrafish and mouse. Time-lapse live imaging reveals that during early craniofacial development, myoblasts condense into round clusters corresponding to future muscle groups. These clusters undergo oriented stretch and alignment during embryonic growth. Genetic perturbation of cartilage patterning or size disrupts the directionality and number of myofibrils in vivo. Laser ablation of musculoskeletal attachment points reveals tension imposed by cartilage expansion on the forming myofibers. Application of continuous tension using artificial attachment points, or stretchable membrane substrates, is sufficient to drive polarization of myocyte populations in vitro. Overall, this work outlines a biomechanical guidance mechanism that is potentially useful for engineering functional skeletal muscle.
- MeSH
- Zebrafish * genetics MeSH
- Muscle, Skeletal * physiology MeSH
- Morphogenesis MeSH
- Myoblasts physiology MeSH
- Myofibrils physiology MeSH
- Mice MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
Hypertrophic cardiomyopathy (HCM) is a common inherited heart disease with an estimated prevalence of up to 1 in 200 individuals. In the majority of cases, HCM is considered a Mendelian disease, with mainly autosomal dominant inheritance. Most pathogenic variants are usually detected in genes for sarcomeric proteins. Nowadays, the genetic basis of HCM is believed to be rather complex. Thousands of mutations in more than 60 genes have been described in association with HCM. Nevertheless, screening large numbers of genes results in the identification of many genetic variants of uncertain significance and makes the interpretation of the results difficult. Patients lacking a pathogenic variant are now believed to have non-Mendelian HCM and probably have a better prognosis than patients with sarcomeric pathogenic mutations. Identifying the genetic basis of HCM creates remarkable opportunities to understand how the disease develops, and by extension, how to disrupt the disease progression in the future. The aim of this review is to discuss the brief history and recent advances in the genetics of HCM and the application of molecular genetic testing into common clinical practice.
- MeSH
- Genetic Testing * MeSH
- Cardiomyopathy, Hypertrophic diagnosis genetics MeSH
- Humans MeSH
- Mutation * MeSH
- Sarcomeres genetics MeSH
- Muscle Proteins genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
BACKGROUND: Little is known about the impact of trans-acting genetic variation on the rates with which proteins are synthesized by ribosomes. Here, we investigate the influence of such distant genetic loci on the efficiency of mRNA translation and define their contribution to the development of complex disease phenotypes within a panel of rat recombinant inbred lines. RESULTS: We identify several tissue-specific master regulatory hotspots that each control the translation rates of multiple proteins. One of these loci is restricted to hypertrophic hearts, where it drives a translatome-wide and protein length-dependent change in translational efficiency, altering the stoichiometric translation rates of sarcomere proteins. Mechanistic dissection of this locus across multiple congenic lines points to a translation machinery defect, characterized by marked differences in polysome profiles and misregulation of the small nucleolar RNA SNORA48. Strikingly, from yeast to humans, we observe reproducible protein length-dependent shifts in translational efficiency as a conserved hallmark of translation machinery mutants, including those that cause ribosomopathies. Depending on the factor mutated, a pre-existing negative correlation between protein length and translation rates could either be enhanced or reduced, which we propose to result from mRNA-specific imbalances in canonical translation initiation and reinitiation rates. CONCLUSIONS: We show that distant genetic control of mRNA translation is abundant in mammalian tissues, exemplified by a single genomic locus that triggers a translation-driven molecular mechanism. Our work illustrates the complexity through which genetic variation can drive phenotypic variability between individuals and thereby contribute to complex disease.
- MeSH
- Organelle Biogenesis MeSH
- Genetic Variation MeSH
- Peptide Chain Initiation, Translational * MeSH
- Cardiomegaly genetics metabolism pathology MeSH
- Rats MeSH
- Quantitative Trait Loci * MeSH
- RNA, Small Nucleolar genetics metabolism MeSH
- RNA, Messenger genetics metabolism MeSH
- Myocardium metabolism pathology MeSH
- Mice, Inbred C57BL MeSH
- Mice, Knockout MeSH
- Mice MeSH
- Rats, Inbred SHR MeSH
- Rats, Transgenic MeSH
- Gene Expression Regulation MeSH
- Ribosomal Proteins genetics metabolism MeSH
- Ribosomes genetics metabolism pathology MeSH
- Saccharomyces cerevisiae genetics metabolism MeSH
- Sarcomeres metabolism pathology MeSH
- Gene Expression Profiling MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
This paper aimed to investigate the dose-effects of l-Lysine (Lys, 0.2% to 0.8%) on the water holding capacity (WHC), textural properties, water mobility and distribution, microstructures and sensory acceptance of reconstructed ham with 50% reduction of added salt. Results showed that reducing salt from 2.50% to 1.25% caused significant increase in cooking loss and centrifuge loss, and decrease in hardness, springiness and chewiness. 0.8% Lys significantly improved the WHC and textural properties of salt-reduced hams, whereas 0.2% Lys further impaired these attributes. Moreover, 0.8% Lys improved the sensory scores for mouthfeel, appearance, taste and global acceptance. The NMR analysis reveals that water distribution and mobility were affected by salt reduction and Lys addition, and hams with 0.8% Lys contained more entrapped water with decreased mobility. Furthermore, a fine network with more bridge-linkage among myofibrils was formed in hams with 0.8% Lys. Therefore, addition of 0.8% Lys showed great potential in developing salt-reduced reconstructed ham with premium technological and sensory qualities.
- MeSH
- Phenotype MeSH
- Muscle, Smooth MeSH
- Humans MeSH
- Myofibrils * MeSH
- Aortic Diseases * MeSH
- Muscle Contraction MeSH
- Check Tag
- Humans MeSH
- Publication type
- Comment MeSH
- Editorial MeSH
- MeSH
- Adenosine Diphosphate biosynthesis physiology metabolism MeSH
- ATP Synthetase Complexes biosynthesis physiology metabolism MeSH
- Energy Metabolism MeSH
- Muscle Fibers, Skeletal physiology metabolism MeSH
- Muscle, Skeletal * cytology physiology metabolism MeSH
- Creatine Kinase, Mitochondrial Form MeSH
- Creatine Kinase * biosynthesis physiology metabolism MeSH
- Humans MeSH
- Myofibrils physiology metabolism MeSH
- Myosins MeSH
- Mitochondria, Muscle physiology metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Endotoxin administration is frequently used as a model of systemic inflammatory response which is considered the important pathogenetic factor in muscle wasting development in severe illness, such as sepsis, cancer, injury, AIDS and others. The main purpose of this study was determining the effect of various doses of endotoxin on protein and amino acid metabolism in two types of rat skeletal muscle. Sepsis was induced by intraperitoneal administration of endotoxin in a dose of 1, 3 and 5 mg/kg body weight (bw); control animals received a corresponding volume of the saline solution. After 24 h, extensor digitorum longus (EDL) and soleus (SOL) muscles were isolated and used for determination of total and myofibrillar proteolysis, protein synthesis, activity of cathepsins B and L, chymotrypsin-like activity of proteasome and amino acid release. The endotoxemia induced the body weight loss, the rise of total cholesterol and triglyceride plasma concentration and the protein catabolic state in skeletal muscle, which was caused by a higher increase in protein breakdown (due to activation of the proteasome system) than protein synthesis. The more significant effect of endotoxin was seen in EDL than SOL. The dose of 5 mg of endotoxin/kg bw induced the most significant changes in parameters of the protein and amino acid metabolism measured and could be therefore considered appropriate for studies of protein catabolism in young rat skeletal muscle at 24 h after endotoxin treatment.
- MeSH
- Endotoxins pharmacology MeSH
- Cathepsin B metabolism MeSH
- Muscle, Skeletal metabolism MeSH
- Rats MeSH
- Myofibrils metabolism MeSH
- Rats, Wistar MeSH
- Proteasome Endopeptidase Complex metabolism MeSH
- Sepsis metabolism MeSH
- Muscle Proteins metabolism MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
