TROPONINS AND SKELETAL MUSCLE PATHOLOGIES

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Abstract

Skeletal muscles account for ~30-40% of the total weight of human body and are responsible for its most important functions, including movement, respiration, thermogenesis, and glucose and protein metabolism. Skeletal muscle damage negatively impacts the whole-body functioning, leading to deterioration of the quality of life and, in severe cases, death. Therefore, timely diagnosis and therapy for skeletal muscle dysfunction are important goals of modern medicine. In this review, we focused on the skeletal troponins that are proteins in the thin filaments of muscle fibers. Skeletal troponins play a key role in regulation of muscle contraction. Biochemical properties of these proteins and their use as biomarkers of skeletal muscle damage are described in this review. One of the most convenient and sensitive methods of protein biomarker measurement in biological liquids is immunochemical analysis; hence, we examined the factors that influence immunochemical detection of skeletal troponins and should be considered when developing diagnostic test systems. Also, we reviewed the available data on the skeletal troponin mutations that are considered to be associated with pathologies leading to the development of diseases and discussed utilization of troponins as drug targets for treatment of the skeletal muscle disorders.

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About the authors

A. P. Bogomolova

Lomonosov Moscow State University; Hytest Ltd.

Author for correspondence.
Email: bogomolova.agnessa@yandex.ru

Faculty of Biology, Lomonosov Moscow State University

Russian Federation, 119234 Moscow; Turku, Finland

I. A. Katrukha

Lomonosov Moscow State University; Hytest Ltd.

Email: bogomolova.agnessa@yandex.ru

Faculty of Biology, Lomonosov Moscow State University

Russian Federation, 119234 Moscow; Turku, Finland

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2. Fig. 1. Alignment of three human TnI isoforms: bcTnI, mTnI, and cTnI. Amino acid sequences of proteins from the Uniprot database: bcTnI (TNNI2_HUMAN, P48788), mTnI (TNNI1_HUMAN, P19237), cTnI (TNNI3_HUMAN, P19429). The alignment was performed using the Clustal Omega program. The matching amino acid residues are marked in blue. The rectangles indicate the boundaries of the α-helices (the amino acid residue numbering is given for the bcTnI sequence). The arrows indicate the binding sites of TnC and TnT. The possible sites of bcTnI and mTnI phosphorylation (p) and bcTnI glutathionylation (glut) are indicated above the sequences [44–47].

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3. Fig. 2. Alignment of three human TnT isoforms: bcTnT, msTnT, and cTnT. Protein sequences were taken from the Uniprot database: bcTnT (TNNT3_HUMAN, P45378-3), msTnT (TNNT1_HUMAN, P13805-1), cTnT (TNNT2_HUMAN, P45379-6). The longest splice forms present in the adult human body were selected (for bcTnT and cTnT – those not containing fetal exons). The alignment was performed using the Clustal Omega program. Identical amino acid residues are highlighted in green. The exonic structure of bcTnT and msTnT is shown above the alignment. Rectangles denote the boundaries of α-helices (the aa numbering is given for the bcTnT sequence), the site of interaction with TnI and TnC is marked above H2. The site of interaction with tropomyosin Tm1 is marked by an oval with a solid line, the ovals with a dotted line indicate the putative binding sites with tropomyosin Tm2 and a possible binding site with nebulin. Possible phosphorylation sites of bcTnT are indicated above the sequences [46, 47, 60, 63–66, 69, 70]

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4. Fig. 3. Alignment of two human TnC isoforms: bcTnC and ms/cTnC. The sequences are taken from the Uniprot database: bcTnC (TNNC2_HUMAN, P02585), ms/cTnC (TNNC1_HUMAN, P63316). Identical amino acid residues are highlighted in yellow. Residues involved in Ca2+ and Mg2+ binding are highlighted in bold. Rectangles mark the boundaries of α-helices (N, A–H). Arrows indicate the N-terminal and C-terminal domains, as well as the EF hands. Ca2+ and Mg2+ binding sites are marked by gray circles; an open circle with a solid line indicates a site specific for Ca2+ in both TnC isoforms; The circle with a dotted line marks the site that selectively binds Ca2+ in bsTnC (the EF-hand in ms/cTnC does not bind ions) [46, 47, 62, 86–89]

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