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Myosin heavy chain (MHC) is a critical component of muscle contraction. MHC is the motor protein of the myosin filament and is the major contractile protein of the sarcomeric thick filament. MHC is involved in the contractile properties of muscle fibres, with MHC I fibres generally being slow-contracting and MHC II fibres faster and more powerful. MHC expression is also implicated in inflammatory myopathies, with overexpression leading to muscle inflammation and damage. MHC expression is also associated with dermatomyositis (DM), with MHC I overexpression detected in muscle biopsies from patients with clinical features of DM.
| Characteristics | Values |
|---|---|
| Full Form | Major Histocompatibility Complex |
| Types | MHC I, MHC II, MHC IIa, MHC IIx, MHC IIAX, MHC IIXA, MHC 2X |
| Muscle Types | Skeletal Muscle, Cardiac Muscle, Smooth Muscle |
| Skeletal Muscle Composition | Type 1, 2A and 2B fibres, with different myosin heavy chain (MHC) composition |
| Cardiac Muscle Composition | α-cardiac MHC (α-MHC, encoded by MYH6) and β-cardiac MHC (β-MHC, encoded by MYH7) |
| Role in Skeletal Muscle | MHC I and II are complementary diagnostic tools for inflammatory myopathy |
| Role in Cardiac Muscle | Mutations in MYH7 are associated with severe forms of HCM |
| Role in Smooth Muscle | N/A |
| Induction of MHC Expression | Cytokines, infectious agents, tissue injury, regeneration |
| Effects of Overexpression | Muscle cell damage, muscle inflammation, T cell-mediated cytotoxicity |
| Effects of Aberrant Expression | Attenuation of muscle regeneration, deleterious effects on muscle repair |
| Effects of Exercise | Type IIX fibres may transform into type IIA fibres, enhancing oxidative capacity |
| MHC Fiber Type Determination | Immunohistochemical staining for myosin heavy chain (MHC) type |
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What You'll Learn
MHC and myogenesis
Myosin heavy chain (MHC) is a protein involved in muscle contraction. MHC isoforms are expressed during myogenesis, the process by which muscle fibres are formed from the fusion of developmental myoblasts. Myoblasts are the only myogenic cells that express significant levels of MHC protein during muscle regeneration. MHC expression is developmentally regulated during this process, with significant levels only in myoblasts.
MHC expression is also implicated in inflammatory myopathies, such as dermatomyositis (DM), polymyositis, and inclusion body myositis. In these diseases, MHC expression is aberrant and upregulated, leading to muscle inflammation and damage. The mechanisms responsible for this aberrant expression are not fully understood, but it is believed that cytokines may play a role in upregulating MHC expression and contributing to deleterious effects on muscle repair.
In studies of mouse muscle cell lines, distinct patterns of MHC isoform expression were observed, indicating that MHC expression is regulated during myogenesis. Furthermore, MHC expression has been shown to be necessary for T cell-mediated cytotoxicity in myopathies.
MHC typing is one method used to classify muscle fibres, and it involves determining different MHC isoforms through myosin heavy chain staining. MHC type is the primary determinant of ATPase activity, which is associated with contraction speed. Type I fibres, or "slow-twitch" fibres, have low ATPase activity and are better suited for prolonged work due to their greater number of mitochondria and capillaries. Type II fibres are further classified into subtypes, such as IIA and IIX, which may be influenced by endurance training.
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MHC and inflammatory myopathies
The Major Histocompatibility Complex (MHC) is a group of genes found in most vertebrates, including humans. MHC molecules are present on the surface of cells and play a crucial role in the immune system by presenting antigenic peptides to T cells, which can then trigger an immune response. In the context of muscle, MHC class I molecules are typically not expressed in normal muscle fibres. However, their re-expression is a notable feature of inflammatory myopathies.
Inflammatory myopathies are a group of autoimmune diseases that include dermatomyositis (DM), polymyositis, and inclusion body myositis. These diseases are characterised by muscle inflammation and damage, and MHC class I molecules play a significant role in their pathogenesis. MHC class I upregulation has been observed in muscle biopsies from patients with inflammatory myopathies, and this upregulation is believed to be associated with the disease process.
Several studies have investigated the role of MHC class I in inflammatory myopathies using mouse models. In one study, transgenic mice expressing MHC class I molecules (H-2Kb) were used to demonstrate that MHC class I upregulation resulted in muscle cell damage, muscle inflammation, and the development of myositis. Similarly, another study on lymphocyte-deficient mice showed that overexpression of MHC class I led to a severe myopathy accompanied by the unfolded protein response (UPR). This response was attributed to the accumulation of H-2Kb molecules in the cytoplasm, which also occurs in some patients with inclusion body myositis.
The mechanisms underlying the induction of MHC class I expression in inflammatory myopathies are not yet fully understood. It has been proposed that MHC class I expression may be triggered by infectious agents or cytokines present in the inflammatory infiltrates in the muscle. Additionally, MHC class I expression could be a nonspecific response to tissue injury and regeneration. Further research is needed to elucidate the exact mechanisms involved.
In summary, MHC class I expression plays a significant role in the pathogenesis of inflammatory myopathies, and its upregulation is a notable feature of these diseases. While the exact mechanisms remain to be fully elucidated, MHC class I expression contributes to muscle inflammation and damage, making it a potential target for therapeutic interventions in inflammatory myopathies.
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MHC and dermatomyositis
Dermatomyositis (DM) is an idiopathic inflammatory myopathy (IIM) with characteristic skin features and heterogeneous systemic manifestations. The pathogenesis of DM is multifactorial and not entirely understood, but it is believed to be influenced by genetic, environmental, and immunological factors. Genetic contributions are supported by observed associations with major histocompatibility complex (MHC) polymorphisms and human leukocyte antigen alleles. MHC-I antigens are expressed in the sarcolemma and/or sarcoplasm of patients with dermatomyositis.
MHC-I expression has been observed in muscle biopsies of patients with dermatomyositis, with higher expression levels in juvenile dermatomyositis compared to adult dermatomyositis. MHC-I upregulation is a typical finding in dermatomyositis muscle pathology and has been proposed as a potential mechanism for myocyte damage. The presence of MHC-I antigens and CD4 expression may increase the suspicion of dermatomyositis during diagnosis.
In a study of 28 untreated adult dermatomyositis patients and 28 juvenile dermatomyositis patients, MHC I and II were expressed in the muscle fibers, with greater MHC I expression in juvenile dermatomyositis and greater MHC II expression in adult dermatomyositis. This distinct pattern of MHC expression was observed regardless of clinical, laboratory, or histological features.
The canine model of dermatomyositis also demonstrates a significant association with a haplotype of the major histocompatibility complex (MHC), providing further evidence of the genetic underpinnings of the disease. Treatment options for dermatomyositis have remained largely unchanged, and there is a need for more targeted and effective therapies.
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MHC and muscle contraction
The myosin heavy chain (MHC) is the major contractile protein of the sarcomeric thick filament and is a critical component to sustain muscle contraction. MHC is the motor protein of the myosin filament, and the human skeletal muscles express three different isoforms: MHC I, MHC IIa, and MHC IIx. MHC type is the primary determinant of ATPase activity, with Type I fibres having a lower speed of contraction and slower ATPase activity compared to Type II fibres. MHC I fibres have been shown to be slow contracting, while MHC IIa and MHC IIx fibres are generally faster and more powerful.
The functional significance of the MHC isoform for its contractile characteristics is well established, and considerable functional adaptability within both MHC I and II fibres has been observed in response to acute exercise. For instance, prolonged exercise has been shown to acutely compromise the maximum Ca2+-activated force in single fibres from highly trained endurance athletes, whereas the Ca2+ sensitivity has been shown to be acutely increased in response to high-intensity exercise.
MHC I fibres in the arm muscle exhibited a higher specific force-generating capacity and greater Ca2+ sensitivity than the same type of fibre in the leg, with no such difference in the case of MHC II fibres. The maximal Ca2+-activated force was greater for MHC II than MHC I fibres in both the arm and leg muscles, with the specific force of MHC II fibres also higher than that of MHC I fibres.
Mammalian skeletal muscles consist of three main fibre types, Type 1, 2A, and 2B fibres, with different MHC composition. Type 2X fibres, which are widely distributed in rat skeletal muscles, can be distinguished from 2A and 2B fibres by histochemical ATPase activity and their unique staining pattern with seven anti-MHC monoclonal antibodies. The heart muscle is composed of two MHC isoforms: α-cardiac MHC (mainly expressed in the atrium) and β-cardiac MHC (found predominantly in the ventricles).
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MHC and muscle fibre typing
The myosin heavy chain (MHC) is the major contractile protein of the sarcomeric thick filament and is a critical component for muscle contraction. MHC fibre typing is one of the methods for classifying skeletal muscle fibres, which are part of the voluntary muscular system and are attached to bones by tendons.
MHC fibre typing is closely related to myosin ATPase activity, which is commonly referred to as "fibre type". MHC fibre typing is determined by the different MHC isoforms, which are the primary determinant of ATPase activity. There are three main fibre types: type 1, type 2A, and type 2B, each with a different MHC composition. Type 2X fibres, found in rat skeletal muscles, are a newly identified fibre type with a unique MHC isoform.
MHC I fibres are slow-contracting, while MHC IIa and MHC IIx fibres are faster and more powerful. The force-generating capacity and Ca2+ sensitivity of these fibres have been studied in arm and leg muscles of highly trained cross-country skiers, revealing that MHC II fibres have a higher maximum Ca2+-activated force than MHC I fibres. However, MHC I fibres exhibit a higher specific force-generating capacity and greater Ca2+ sensitivity than MHC II fibres in the arm muscle, but not in the leg muscle.
MHC expression has been observed in inflammatory myopathies, such as dermatomyositis (DM), polymyositis, and inclusion body myositis. Overexpression of MHC in muscle biopsies from patients with DM has been detected, and it is suggested that this could be due to the diffusion of secreted cytokines by inflammatory cells near the biopsied muscle area. Furthermore, class I MHC expression may play a role in initiating and maintaining muscle damage in myositis.
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Frequently asked questions
MHC stands for myosin heavy chain. It is the major contractile protein of the sarcomeric thick filament and is critical for muscle contraction.
There are three types of MHC isoforms: MHC I, MHC IIa, and MHC IIx. MHC I is slow contracting, while MHC IIa and MHC IIx are faster and more powerful.
MHC is the motor protein of the myosin filament. The contractile properties of muscle fibres depend on their expression of different MHC isoforms. MHC distribution, however, is not explanatory for muscle function.
