Skeletal Muscle
Nassir H. Sabah in Neuromuscular Fundamentals, 2020
A thin filament is about 5–6 nm in diameter, 1 µm long, and consists mainly of a strand of F-actin (F for fibrous), as illustrated in Figure 9.4b. A strand of F-actin is a polymer composed of two twisted rows of 300–400 individual molecules of G-actin (G for globular), each molecule having a diameter of about 5 nm and a molecular weight of about 42 kdaltons. The F-actin strand is held together by a thread of nebulin that extends along the F-actin between the two rows of G-actin molecules. Each G-actin molecule has an active site that can bind to the head of a myosin molecule but is prevented from doing so under resting conditions, when there is no contraction, by tropomyosin molecules that cover the active sites. A tropomyosin molecule is a double strand that joins head-to-tail with other tropomyosin molecules to form a twisted strand over the length of the F-actin. Each tropomyosin molecule covers seven active sites and is bound to a troponin molecule. A troponin molecule is composed of three largely globular subunits: (i) troponin T (tropomyosin-binding troponin) that forms a troponin-tropomyosin complex, (ii) troponin C (Ca2+ binding troponin) that plays a major role in contraction, as explained later, and (iii) troponin I (inhibitory troponin) that is attached to G-actin in the absence of Ca2+ and holds the tropomyosin in a position that blocks myosin from reaching the active sites on G-actin. When Ca2+ bind to troponin C, troponin I detaches from the actin, thereby allowing the tropomyosin to move over the surface of the thin filament.
Food allergens
Richard F. Lockey, Dennis K. Ledford in Allergens and Allergen Immunotherapy, 2020
Shrimp is the most studied of the Crustacea allergens, and tropomyosins are the major allergens. Tropomyosin is an actin-binding protein important in regulating muscle contractions. The IgE-binding epitopes of the shrimp allergen Pen a 1, a 36 kDa tropomyosin, are known [54,55]. The deduced amino-acid sequence of 284 amino acids from recombinant allergens and amino acid sequences from allergenic and nonallergenic vertebrate tropomyosins reveal 80%–99% and 51%–58% amino acid sequence homology, respectively. Analysis of the secondary structure of Pen a 1 shows an α-helical conformation that is typical for tropomyosins [56]. Tropomyosin allergens in lobster (Hom a 1) and crab (Cha f 1) have also been identified. Tropomyosin is also a pan-allergen for fish (tilapia, cod, albacore, and swordfish) [57,58] and mollusks (squid [59], oyster [60], and snail [61]). Several other allergens in shrimp and lobster are arginine kinase, myosin light chain 1 and 2, troponin C, and sarcoplasmic calcium-binding protein [14]. Arginine kinase, a major allergen in insect [62] and house dust mite [63] allergy is also a mollusk allergen found in octopus [64], thus causing cross-reactivity [65].
Cardiac and cardiovascular disorders
Angus Clarke, Alex Murray, Julian Sampson in Harper's Practical Genetic Counselling, 2019
Hypertrophic cardiomyopathy (HCM) in older children and young adults is not rare (prevalence around 1 in 500 prevalence) and often appears to be inherited as a variable autosomal dominant trait (in about two-thirds of those affected). Penetrance is often higher if the family is studied by echocardiography but only around 25% if defined by clinical presentation; that is, there is a risk of approximately one in eight for clinical disease in first-degree relatives. Specific mutations at the myosin β-heavy chain locus have been identified in some families, while others result from defects in tropomyosin, troponin and a longer list of less commonly involved genes. Finding a clearly pathogenic mutation in a known gene can be a great help in assessing unaffected family members and in genetic counselling; it may also help the cardiologist to assess the likely prognosis and thereby inform decisions of management. One of the benefits of NGS gene panel testing for these disorders is that their apparently variable penetrance can be seen in some families to result from the involvement of variants at more than one locus. Thus, some cases seem to arise through a form of digenic inheritance.
Alterations in the expression pattern of RBC membrane associated proteins (RMAPs) in whole body γ-irradiated Sprague Dawley rats
Published in International Journal of Radiation Biology, 2023
Prabuddho Mukherjee, Kamendra Kumar, Bincy Babu, Jubilee Purkayastha, Sudhir Chandna
A closer look at the radiation-response of all candidate proteins detected in this study (Figure 3) reveals that at the sub-lethal dose of 2 Gy, a set of five proteins namely PRDX2, PSMD14, EXOSC6, ALB and TPM1 were up-regulated at different time-points. Out of these, ALB and EXOSC6 were up-regulated only at 2 Gy and did not show any response at the higher doses. At the highest dose of 7.5 Gy, TPM3 and PRDX2 were the two proteins primarily up-regulated at all time-points. Interestingly, PSMD14, which responded to sub-lethal (2 Gy) dose with highest up-regulation at 48 h, was distinctly non-responsive at 48 h following lethal (7.5 Gy) dose. The two tropomyosin chains identified showed different expression patterns. While TPM1 had elevated levels at all time-points for sub-lethal as well as lethal doses tested, TPM3 was over-expressed in a dose-dependent manner at the two higher doses only.
Proteomic profiling of giant skeletal muscle proteins
Published in Expert Review of Proteomics, 2019
Sandra Murphy, Paul Dowling, Margit Zweyer, Dieter Swandulla, Kay Ohlendieck
Recent developments in the field of muscle biology that have applied a TDP approach included results published on tropomyosins present in different skeletal muscles from multiple species, including swine, rat and human [43]. This study revealed that tropomyosin isoforms Tpm1.1 and Tpm2.2 are the two major Tpm isoforms in swine and rat skeletal muscles, whereas Tpm1.1, Tpm2.2, and Tpm3.12 are present in human skeletal muscles. This methodology provides an analytical foundation for further studies on these tropomyosin isoforms in muscle-related diseases. A quantitative TDP approach identified significant changes in post-translational modifications of critical myofilament proteins in predominantly fast-twitching skeletal muscles of aging rats, together with age-related alterations in the phosphorylation of isoforms of the Z-disk associated protein Cypher [44].
UR-144, synthetic cannabinoid receptor agonist, induced cardiomyoblast toxicity mechanism comprises cytoplasmic Ca2+ and DAPK1 related autophagy and necrosis
Published in Toxicology Mechanisms and Methods, 2023
Muzeyyen Akar, Merve Ercin, Tugce Boran, Selda Gezginci-Oktayoglu, Gül Özhan
The troponin complex is a very important regulatory unit for heart muscle contractility. Troponin T is critical for actin-myosin interactions in heart muscle, binds to actin filaments and also interacts with tropomyosin in the muscle. After Ca2+ binds to troponin C, conformational change occurs in the complex, and heart muscle can contract (Sharma et al. 2004; Marques and de Olivera 2016). Moreover, troponin T is a specific biomarker of cardiac damage. Troponin T is secreted from cytosol to plasma in myocardial damage (Mair et al. 1992). Accordingly, the present study evaluated the released and cytoplasmic troponin T levels at 200 μM UR-144 dose in order to show the toxic effects of UR-144 on cardiomyoblasts. According to our results, both released and cytosolic troponin T levels showed a significant increase following 200 μM UR-144 treatment. Similarly, released troponin T level is reported to be low in healthy subjects (Frankenstein et al. 2011). The intracellular Ca2+ level has great importance in cardiac muscle contractility. Impaired Ca2+ regulation in cytosol is associated with many cardiac diseases, such as ischemia-reperfusion injury and heart failure. Increase in Ca2+ level may result in the activation of many signaling pathways that lead to loss of cardiomyocytes in the heart (Marks 2003; Zucchi et al. 2003). According to our results, intracellular Ca2+ levels increased at 200 μM UR-144 compared to the control group. The necrosis and autophagy stimulating effects of UR-144 at 200 μM concentration may be associated with Ca2+-dependent signaling pathways.