China
Africa
Explore chapters and articles related to this topic
Biochemical Contributors to Exercise Fatigue
Published in Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse, The Routledge Handbook on Biochemistry of Exercise, 2020
Arthur J. Cheng, Maja Schlittler, Håkan Westerblad
Most everyday activities such as walking and running involve brief, repeated activation of muscles. During locomotion, the rate at which energy in the form of adenosine triphosphate (ATP) is delivered to energy-consuming ion pumps and molecular motors, i.e., the myosin cross-bridges, increases dramatically in skeletal muscle. In fact, the rate of ATP turnover can increase more than 100-fold when a muscle goes from the resting to the fully activated contracting state, and this can occur within a few milliseconds and without any major change in the cellular ATP concentration (74). However, this effective metabolic system comes with a price: Highly energy-demanding physical exercise requires a rate of ATP delivery that exceeds the capacity of aerobic energy metabolism of the muscle fibres, and the additional anaerobic metabolism results in end products that make contractions weaker and slower; that is, peripheral fatigue develops. In addition, the performance during physical exercise can be limited by impaired neuronal activation of muscles, and this is referred to as central fatigue (31).
Genomics and Hearing Loss: Toward a New Standard of Care?
Published in Stavros Hatzopoulos, Andrea Ciorba, Mark Krumm, Advances in Audiology and Hearing Science, 2020
Myosins are actin-based molecular motors that regulate several processes, such as the rearrangement of the actin cytoskeleton, the regulation of tension of actin filaments and the transport of organelles. Several mutations affecting the myosins are well identified (MYO3A, MYO6, MYO7A, and MYO15A for example). Most of the mutations in MYO7A cause Usher syndrome type I, an autosomal recessive genetic disorder characterized by congenital, bilateral, profound sensorineural hearing loss, vestibular areflexia, and adolescent-onset retinitis pigmentosa. Usher syndrome represents about half of cases where both blindness and hearing impairments are present.
Mitochondrial Pathologies and Their Neuromuscular Manifestations
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
Carlos Ortez, Andrés Nascimento
Indirectly, mitochondria dysfunction could be involved by mutations in genes encoding molecular motors of anterograde and retrograde transport. A missense mutation in KIF1B-beta, a monomeric motor for anterograde transport of mitochondria, has been identified in affected members of a Japanese family presenting an autosomal dominant CMT2A1 resulting in a p.Gln98Leu substitution150. Dynein heavy chain 1 (DYNC1H1)
Misconnecting the dots: altered mitochondrial protein-protein interactions and their role in neurodegenerative disorders
Published in Expert Review of Proteomics, 2020
Mara Zilocchi, Mohamed Taha Moutaoufik, Matthew Jessulat, Sadhna Phanse, Khaled A. Aly, Mohan Babu
Additionally, overexpression or mutations in α-Syn impact mt fragmentation as observed in several cell lines and human samples, revealing a role for altered α-Syn in impaired mt dynamics observed in PD [152–154]. α-Syn aggregation is also observed in PD, which impairs the anterograde-to-retrograde mt flux and causes transport defects [152,155]. Indeed, this PD-related protein interacts with the molecular motor machinery and disrupts the association of kinesin-1 motors and microtubules, damaging the transport of mt and other neuronal cargo mechanisms [156,157]. Similar to α-Syn, mutations in CHCHD2 (coiled-coil-helix-coiled-coil-helix domain containing 2) cause the onset of autosomal dominant PD due to impaired energy metabolism [158]. Under physiological conditions, CHCHD2 directly binds to mt complex IV subunits (cytochrome c oxidase, a respiratory chain complex) and this interaction is necessary for complex IV activity [159]. Accordingly, CHCHD2 knockdown cells show reduction in the levels of both, complex I and IV [159,160], alterations in mt morphology, impaired oxygen respiration, loss of dopaminergic neurons, and motor deficits in Drosophila, similar to PD-associated symptoms, revealing a role for altered CHCHD2 in rewiring of mtPPIs in PD with notable impairment in energy metabolism [158].
Lower expression of prestin and MYO7A correlates with menopause-associated hearing loss
Published in Climacteric, 2019
H. Diao, L. Zhao, L. Qin, W. Bai, K. Wang, J. Zhang, X. Chen, H. Jiang, L. Mao
The estrogen receptor (ER) is distributed in the hair cells of the cochlea. ERα is involved in transmission of the cochlear and vestibular signals, and ERβ may have neuroprotective effects on the inner ear8. The high-frequency hearing loss is due to the loss of high-frequency signals during the transmission of the cochlea. So, the impact of ERα on menopausal hearing loss is important. Damage and dysfunction of hair cells have a direct correlation with hearing loss. Human myosin VIIA (MYO7A) is a member of the unconventional myosin superfamily of proteins. It is an actin-binding molecular motor that uses the enzymatic conversion of adenosine triphosphate to adenosine diphosphate and inorganic phosphate to provide energy for movement9,10. Mutations in MYO7A are responsible for Usher syndrome – a condition characterized by congenital hearing loss in humans. There is a known association between sarcopenia and hearing thresholds in postmenopausal women11. Muscle strength in menopausal women declines with age due to the reduction in ovarian hormone secretion12. Prestin is a motor protein, expressed in the basolateral plasma membrane of cochlear outer hair cells (OHCs). It underlies the generation of somatic, voltage-driven mechanical force which is the basis for the exquisite sensitivity, frequency selectivity, and dynamic range of mammalian hearing13,14. Clinical research shows that low estrogen levels and abnormal hair cell function can lead to a high-frequency hearing loss. Prestin is also known to be affected by hormones (thyroid hormone, melatonin, etc.)15,16. Therefore, it may be hypothesized that low estrogen levels may affect MYO7A and prestin in the cochlea, leading to hearing impairment.
The platelet shape change: biophysical basis and physiological consequences
Published in Platelets, 2019
Alexander E. Moskalensky, Alena L. Litvinenko
Another mechanism undermining the equilibrium is weakening of the marginal band, i.e., lowering the flexural rigidity κ. For instance, the increase of [Ca2+]i may directly cause the depolymerization of tubulin [39,40]. Indeed, some studies revealed the transient disassembly of microtubules during the shape change [41,42]. The Rho-kinase mediated pathway may also contribute to the tubulin depolymerization [43]. Finer microtubule rings have impaired ability to withstand the elastic shell tension. When the cortex forces overcome the new, lower threshold value, the marginal band becomes unstable and buckles following slight deviation from symmetrical state. Experimental observations by Diagouraga et al. [6] revealed that it coils in a saddle-shaped structure. The authors also showed that the action of molecular motors is necessary for this coiling. The treatment of platelets with erythro-9-[3–2-(hydroxynonyl)] adenine, a dynein inhibitor, prevented the marginal band coiling during activation with ADP. The activation of tubulin motors is likely calcium-dependent, since Ca2+concentration shifts the balance between antagonistic dynein and kinesin [44,45]. These motors induce sliding of microtubules, which hypothetically results in the elongation of the marginal band. The increase of the marginal band radius would also significantly lower the above-mentioned threshold force, since R is raised to the power of minus three at the right-hand side of Eq. (1). At the same time, it additionally stretches the cortex, thereby enhancing cortical tension, and altering the contact angle α. The sliding of microtubules, which are cross-linked by bridge proteins, causes internal stress in the bundle and its deviations from planar state. All these effects finally result in the coiling of the marginal band.