Protein degradation in Muscle atrophy

The human body contains three types of muscle tissues, namely cardiac muscle, smooth muscles and skeletal muscle. Skeletal muscle is the most abundant and is responsible for motor movement. It determines the body’s strength, endurance and overall physical performance. Reduction in muscle mass, or atrophy normally takes place when the rate of protein degradation exceeds the rate of protein synthesis.
This results in the decrease in the cross-sectional area of myofibres and a decrease in muscle strength. Muscle atrophy may occurs due to physiological (aging, sedentary lifestyle) and pathological (chronic diseases) reasons. A lot of research has been conducted to try and understand the mechanisms behind muscle atrophy.
Apart from decrease in cross sectional area of myofibres, muscle atrophy is also characterized by a switch of the fiber type and composition. This has led to inherent deficits in the ‘quality’ of the skeletal muscle affected.
Scientific observations clearly indicate that that atrophy occurs as a result of unrelated mechanisms that may cooperate synergistically. An imbalance of anabolic and catabolic factors that may alter nitrogen balance leading to protein depletion and muscle atrophy.Various triggers for protein degradation have been studied:

a) Myostatin:
Myostatin is a growth factor which regulates muscle size during embryonic development and throughout life. Knock out or mutation of this protein causes the abnormal regulation of muscle growth. Inhibition of this protein has been shown to induce muscle atrophy

b) Glucocorticoids
Glucocorticoids are hormones that influence the metabolism of carbohydrates and sometimes fats and protein .This is an important trigger of muscle atrophy. They decrease the rate of protein synthesis as well as promoting degradation. All types of atrophy have been associated with increased glucocorticoid levels.

b) Cytokines
Cytokines are immune substances that have an effect on other cells in the body. They are a key trigger of muscle wasting. Immunological Studies have shown that there is an increased level of TNF (tumour necrosis factor) and other cytokines e.g. Inter Leukin1 [IL1], Inter Leukin6 [IL6] in patients with cachexia. Administration of TNF had been known to induce cachexia. In mice with cancer or sepsis, blockage of TN F prevents muscle wasting.

 

d) NFα-kB signaling
NFα-kB represents a family of five transcription factors that have been implicated in muscle atrophy. They mediate a variety of processes, One way in which the NFα-kB causes atrophy is through ubiqutination pathway which involves transcriptional signaling of certain proteins. These targeted proteins are destroyed by attaching of up to four types of a small peptide called ubiquitin to a protein substrate.

Flow diagram summarizing the molecular basis of skeletal muscle atrophy

The cellular and molecular causes of atrophy are not limited to those mentioned above. Research is ongoing concerning the specific causes and mechanisms.

 

REFERENCES
Iain W. McKinnell, Michael A. Rudnicki, Molecular Mechanisms of Muscle Atrophy, Cell, Volume 119, Issue 7, 29 December 2004, Pages 907-910, ISSN 0092-8674, 10.1016/j.cell.2004.12.007.
Carmeli E, Reznick AZ. The physiology and biochemistry of skeletal muscle
atrophy as a function of age. Proc Soc Exp Biol Med. 1994 Jun;206(2):103-13.
Review. PubMed PMID: 8208732.

Posted in Muscle atrophy.

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