Myostatin Genetic Essay

Introduction: According to the “Human Physiology Laboratory Manual “,BIOL 282 ,page 31 , the reason of performing this experiment is to learn how the muscle contraction occurs based on the molecular level and what kind of factors are involved .As a matter of fact, skeletal muscles contain a lot of nuclei because of the cell fusion while being developed and are made of cylindrical cells that have myofibrils. The myofibrils contain sarcomeres and the

Muscle fibres, as shown in Diagram 1, consist of myofibrils, which contain the proteins, actin and myosin, in specific arrangements . The diagram illustrates how a muscle is made up of many fascicles, which in turn are made up of many endomysiums, and within them, many muscle fibres. Each muscle fibre is made up of many myofibrils that consist of sarcomeres bound end on end . Actin is a thin filament, about 7nm in diameter, and myosin is a thick filament, about 15nm in diameter , both of which reside in the sarcomere. They are held together by transverse bands known as Z lines . Diagram 2 shows actin and myosin filaments within a sarcomere, and the Z lines that connect them.

Rationale, Significance and Hypothesis. An extrinsic factor, which exerts a dominant influence on skeletal muscle fiber phenotype, is the nervous system. Buller et al. (1960) elegantly demonstrated the plastic nature of skeletal muscle fibers in response to changes in innervation type. Later, Lφmo and Westgaard (Lφmo and Westgaard, 1974; Westgaard and Lφmo, 1988) demonstrated that depolarization of muscle with specific patterns and frequencies of electrical activity are sufficient to cause changes in mature muscle fiber phenotypes. However, how myofibrillar gene expression and structural organization is affected by the frequency of impulses during activity, the amount of activity over time, or other characteristics of patterned activity is essentially unknown. To answer these questions will require the isolation and study of subsets of muscle-specific proteins in relation to different electrical activation patterns in vivo, an issue that cannot be easily addressed in preparations currently used in the study of muscle development and maintenance. However, using novel in vivo approaches can, in part, circumvent this difficulty.

Myofibrils are made up of long proteins that include myosin, titin, and actin while other proteins bind them together. These proteins are arranged into thin and thick filaments that are repetitive along the myofibril in sectors known as sarcomeres. The sliding of actin and myosin filaments along each other is when the muscle is contracting. Dark A-bands and light I-bands reappear along myofibrils. The alignment of myofibrils causes an appearance of the cell to look banded or striated. A myofibril is made up of lots of sarcomeres. As the sarcomeres contract individually the muscle cells and myofibrils shorten in length. The longitudinal section of skeletal muscle exhibits a unique pattern of alternating light and dark bands. The dark staining, A-bands possess a pale region in the middle called the H-zone. In the middle of the H-zone the M-line is found, that displays filamentous structures that can join the thick filaments. The light-staining bands also known as I-bands are divided by thin Z-line. These striated patterns appear because of the presence of myofibrils in the sarcoplasm (IUPUI, 2016).

When a muscle contracts, myosin heads in thick filaments bind to actin in thin filaments and pulls the thin filament, shortening the length of the muscle fiber. However, without Ca++ when troponin binds to actin, the tropomyosin moves into a position that

When a cell becomes damaged and undergoes apoptosis the muscle cells may not be able to regenerate at a proper rate to avoid a deficiency in the amount of the nuclei needed to maintain proper muscle mass. Support for this need and the suggestion that nuclei number may be size limiting and therefore a causation for atrophy was found in the study by the observation of damaged myonuclei were found in stage 3 mice but absent in stage 1, myonuclei reduction in the two muscle samples, nuclear domain size in regards to surface area was either maintained or increased, and the reappearance of a correlation between nuclei number and fiber size in stage 3 muscles. Particularly EDL IIb fibers may be most susceptible to sarcoma due to a generally lower nuclei number and that distribution of these fibers is impaired in the elderly which would not reduce capacity for synthesis but could increase transport distances causing decreased functionality. The nuclear shape also changed which has an unknown impact on functionality and may have been the cause of the nuclear fragmentation possibly leading to

An example of one such category of muscular dystrophy is distal muscular dystrophy. distal muscular dystrophy causes atrophied muscles due to a damaged DYSF or ANO5 gene. The DYSF gene aids in the creation of dysferlin. Dysferlin is found in the thin sarcolemma of the muscle tissue which is thought to aid the sarcolemma in repairing muscles. Since the production of dysferlin is inhibited by this form of muscular dystrophy, the muscles are not able to be repaired, leading them to become progressively more damaged and ineffective over time. Abnormalities in the other ANO5 gene, which produces anoctamin-5 affect muscles by reducing if not eliminating said protein. ANO5 is thought to provide transport for chlorine ions to the muscle cells of a muscle. These two genetic disorders are usually closely linked and it is common for the abnormality of one gene

Actin and myosin filaments can be found in skeletal muscle and are the smallest units that form a sarcomere, which is the smallest contractile unit in muscle (Baechle, 2008). The Sliding Filament Theory states that the actin filaments slide inward on the myosin filaments, pulling on the boundaries of the sarcomere, causing it to shorten the muscle fiber, also known as a concentric muscular contraction (Baechle, 2008). The Sliding Filament Theory is composed of five steps: the “Resting Phase”, the “Excitation-Contraction Coupling Phase”, the “Contraction Phase”, the “Recharge Phase”, and the “Relaxation Phase” (Baechle, 2008). During the Resting Phase, the actin and myosin filaments are lined up with no cross-bridge binding of the two filaments. During the Excitation-Contraction Coupling Phase, Calcium is released from the sarcoplasmic reticulum and binds to troponin, causing a shift in tropomyosin where the binding cites are exposed (Baechle, 2008). When the binding cites are exposed, the myosin cross-bridge head attaches to actin. During the Contraction Phase, ATP bonds break, releasing energy that is used to allow the myosin head to flex, causing the actin filaments to move toward the M-bridge. During the Recharge Phase, there is a continuous repetition of the Excitation-Contraction Coupling Phase and the Contraction Phase in order to produce muscular

Desmin is a type III intermediate filament protein that is muscle-specific and is found in all muscle types: smooth, cardiac, and skeletal. Autosomal dominant and autosomal recessive desmin gene mutations affect desmin (DES) and oftentimes αβ-crystallin (CRYAB), a chaperone for DES, which leads to a type myofibrillar myopathy, known as desminopathy (Goldfarb et al., 2010). Desmin is the most abundant IF protein in striated and smooth muscle cells and is one of the earliest markers of muscle development (Clemen et al., 2012). Desmin filaments are mainly located at the periphery of Z-disk of striated muscles and at the dense bodies of smooth muscle cells, and they have been thought to play a major role in the maintenance of structural and mechanical integrity of the contractile apparatus in muscle tissues (Paulin & Li, 2004). A dysfunctional desmin protein cannot properly interact with Z-discs, leading to abnormalities of sarcomere structure and problems with the formation of myofibrils (NIH, 2016). The resulting pathology, desminopathy, is one of the most common intermediate filament human disorders associated with mutations in closely interacting proteins (Goldfarb & Dalakas, 2009). This condition is defined as skeletal and cardiac myopathy characterized by the presence of chimeric aggregates in muscle fiber areas that consist of DES, CRYAB and other proteins (Goldfarb et al., 2010). While a few desmin-related

1.a) Contractile protein molecules that are seen in skeletal muscle fibres are actin (thin filaments) and myosin (thick filaments). Together, they produce the force of muscle contractions by forming cross bridges, and moving via a power stroke. The regulatory proteins that are seen within a skeletal muscle are troponin and tropomyosin. These proteins play a role in starting or stopping muscle contractions. When a muscle fibre is relaxed, there are no contractions because actin is unable to bind with the cross bridge. This is because tropomyosin covers the myosin binding sites on the actin proteins. In addition, troponin is not bound to calcium when a muscle fibre is relaxed, thus keeping the tropomyosin in its blocking position. When calcium enters the muscle fibres, it binds with troponin. This binding causes the tropomyosin to move away

They include muscle proteins, which are found in other cells and tissues. These proteins are involved in contractile events in the cytoplasm, abling the muscles to move and fix the cells together. Actin is a thin filament and myosin is a thick filament. These are protein filaments that cause contraction of muscles when the filaments slide over each other in a series of repetitive events. This is called the sarcomere. Sarcomere shortens when a myosin heads and a thick myofilaments form cross bridges with actin molecules. A bond with calcium causes troponin to change shape and tropomyosin moves away from the myosin binding site on actin allowing the myosin head to bind actin. This is continuous causing muscle

We used the differentiated cells C2C12 myoblast to help us determine the difference in the muscle cells. These cells are signal through the

The myostatin protein binds to an operator and prevents the gene for muscle growth from being expressed. (Joulia-Ekaza & Cabello 2006)

form of myosin ATP and are not very good at delivering calcium to the muscle

Aim 2: Identify the attributes of distinct electrical activation patterns responsible for the regulation of skeletal muscle phenotype during tail regeneration in adults. The working hypothesis is that the extent to which muscle fibers disassemble their sarcomeres and downregulate their contractile genes during the transformation of muscle fibers to electrocytes is predicted