Genetic testing for talent identification and development
Silvia Camporesi, Mike McNamee in Bioethics, Genetics and Sport, 2018
Direct-to-consumer (DTC) testing that provides analysis of genes in association with sports performance and sports talent is primarily based around the angiotensin I-converting enzyme (ACE) and the gene for α-actinin-3 (ACTN3). The ACE gene was the first to be widely recognised for its association with performance; in particular it was demonstrated to have an association with skeleto-muscle formation and function. In 2003 Yang and colleagues found that both male and female elite sprinters have a significantly higher frequency of the functional 477R genotype, where R stands in place of the amino acid arginine ‘R’ rather than a stop codon in the ACTN3 gene (Yang et al. 2003). Alfa-actinin belongs to a large family of actin-binding proteins, where actin is a fundamental component of the contractile unit of muscle fibres. Polymorphisms in ACTN3 are thought to contribute to the heritability of fibre-type distribution in muscle, where Type I muscle fibres are slow-twitch fibres that use aerobic metabolism and are used in endurance races, while Type II muscle fibres are fast-twitch fibres, which use anaerobic metabolism to create energy and are used in activities requiring short intense effort such as sprints or basketball, football and hockey (Berman and North 2010). Subsequent research has consistently supported the view that the genotypes of ACE and ACTN3 influence human performance in relation to sprint/power or endurance events. Although many genes and allelic variants have been tentatively associated with performance-related traits, these associations have not reached a conclusive level.
The locomotor system
C. Simon Herrington in Muir's Textbook of Pathology, 2020
The largest tissue within the body, muscle, accounting for 40% of an average male's weight, is highly organized to contract, produce movement or stability, and do work. Skeletal muscle consists of long multinucleated syncytia formed by the fusion of columns of single cells. The cytoplasm contains bundles of myosin and actin filaments forming contractile myofibrils. The individual subunit is the sarcomere and these are arranged end to end to form muscle fibres. The parallel alignment of actin and myosin bundles gives a characteristic band-like appearance on light microscopy and alternating dark (A, anisotropic) and light (I, isotropic) bands are seen on electron microscopy. A variety of other proteins including α-actinin and dystrophin are found within muscle cells. The individual muscle fibre is surrounded by the endomysium. Fibres are bound into fascicles by the perimysium, whereas the muscle itself is sheathed by the epimysium.
Integrins, Integrin Regulators, and the Extracellular Matrix
Bruce S. Bochner in Adhesion Molecules in Allergic Disease, 2020
Recently, Lewis and Schwartz (121) mapped association of cytoskeletal elements with β1 in vivo. Colocalization of FAK, talin, and actin with a transfected chicken β1 protein expressed in mouse NIH 3T3 cells was dependent on a common region of the carboxy-terminus of β1, while α-actinin colocalization appeared to require a more membrane-proximal sequence (Fig. 2). These results, in combination with earlier work, led the authors to propose that the carboxy-terminal region, containing two NPXY motifs, is necessary for talin association. Filardo and coworkers (124) showed that similar motifs in the β3 cytoplasmic tail were important for adhesion, spreading, and migration of melanoma cells (Fig. 2). Similarly, several mutations in the NXXY motif of the β3 cytoplasmic tail abolished cell spreading and FAC formation in COS cell transfectants (125). These data assign cytoskeletal interaction roles to these two motifs in the β3 cytoplasmic tail. In addition, mutations in two other regions of β3 (727–733, 752) inhibited β3 integrin recruitment to preformed FACs. This region is homologous to that found in β1 to be important in interactions with α-actinin (119) (Fig. 2).
ACTN3 R577X polymorphism related to sarcopenia and physical fitness in active older women
Published in Climacteric, 2021
C. Romero-Blanco, M. J. Artiga González, A. Gómez-Cabello, S. Vila-Maldonado, J. A. Casajús, I. Ara, S. Aznar
As well as the health benefits of physical activity in the elderly, investigating whether genetics determine better physical fitness or muscle mass8,9 is also of great interest. One of the most studied genetic polymorphisms has been ACTN3 R577X at position 1747 in exon 16, where an arginine turns into a codon stop due to the replacement of a cytosine by a thymine10. Homozygous XX people cannot produce the ACTN3 protein in the muscle, something estimated to take place in approximately 18% of the population11. ACTN3 is a structural protein and the predominant component of the Z areas of the sarcomere; α-actinin-3 deficiency in the general population seems to be connected to an age-related decrease of muscle mass and physical strength12.
Se@SiO2 nanocomposites attenuate doxorubicin-induced cardiotoxicity through combatting oxidative damage
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Guoying Deng, Changzhe Chen, Junjie Zhang, Yue Zhai, Jingpeng Zhao, Anqi Ji, Yingjie Kang, Xijian Liu, Kefei Dou, Qiugen Wang
Primary myocardial cells were acquired from mice. Myocardial cells in the blank group and H2O2 group received no treatments in the first 12 h, while cells from Se@SiO2 group and H2O2 + Se@SiO2 group were treated with 40 μg/ml Se@SiO2 for 12 h. In the subsequent 12 h, the H2O2 and H2O2 + Se@SiO2 group received 50 mM H2O2 for 12 h. After that, the cells were stained and examined according to the manufacturer’s protocol (Abcam, ab66110). Blue fluorescence shows DAPI and red the expression of a-actinin. In each group, several visual fields were selected randomly and images were acquired randomly by a Zeiss LSM710 laser confocal microscope (Carl Zeiss, Germany). Apoptosis rates were determined by the percentages of dead cells from three independent visual fields in each group.
Chondrocyte protein co-synthesis network analysis links ECM mechanosensing to metabolic adaptation in osteoarthritis
Published in Expert Review of Proteomics, 2021
Aspasia Destouni, Konstantinos C. Tsolis, Anastassios Economou, Ioanna Papathanasiou, Charalampos Balis, Evanthia Mourmoura, Aspasia Tsezou
Indentation-type atomic force microscopy in biopsies from OA patients has revealed that the nano-stiffness of damaged cartilage is lower than the healthy non-degraded cartilage and that OA cartilage becomes softer due to progressive disintegration of the collagen meshwork [68]. The observed depletion of ECM and PCM structural components and the concurrent upregulation of CD44, a sensor of ECM integrity indicate a shift toward a low ECM adhesion microenvironment in OA [69]. In low ECM adhesion conditions, integrin signaling has been shown to be dampened and integrin-anchored actin filaments become shorter and fragmented [70]. We observed that key structural components of integrin activation and cytoskeleton remodeling such as, TLN, vinculin (VCL), Rho family GTPases RhoA and Rac1, as well as structural components of F-actin stress fibers and focal adhesions, actinin-α isoform 1 (ACTN1) cluster in the core chondrocyte network (Figure 3a). ACTN1 was found abundant in healthy and depleted in hypertrophic OA chondrocytes, whereas F-actin depolymerizing destrin (DSTN) was abundant in OA chondrocytes (Figure 3a) indicating increased actin remodeling in OA. Although the integrin activator and linker to actin filaments TLN1 is more abundant in OA, VCL which stabilizes the interaction between TLN and the actin cytoskeleton under high tension conditions was depleted in OA chondrocytes. These interactions indicate an adaptation of the ECM-focal adhesion interface to low ECM forces.
Related Knowledge Centers
- Actin
- Microfilament
- Myofilament
- Protein Dimer
- Sarcomere
- Cardiac Muscle
- Alpha-Actinin-1
- Alpha-Actinin-4
- Alpha-Actinin-2
- Alpha-Actinin-3