Regulation of Muscle Hypertrophy Essay Example for Free

Regulation of Muscle Hypertrophy Essay Our skeletal muscles make up 40-50% of our total mass and are essential for all humans to move, breath, and stand up straight. For the first 20 years of our lives and for those physically active after our muscles are continually growing. Satellite cells are responsible for this growth in our skeletal muscle and are referred to as muscle stem cells. When skeletal muscle cells are traumatized due to physical trauma or disease the regeneration process includes three general processes, destruction, regeneration and remodeling. What regulates these three processes? How are they signaled to initiate the cell cycle and what nutrients and systems do they require to carry out the processes of regeneration and growth†? Muscle regeneration is a daily occurrence for almost animals. The complex systems involved in regenerating the organ system that makes up over 40% of our bodies need to communicate properly, understanding how this is done can open doors for recreational and medical opportunities. Main Point: Understanding the regulation of muscle hypertrophy requires an understanding of satellite cells (SC), the environment they reside in (niche) and the growth factors that stimulate and inhibit their activation. Sub Point: Satellite Cells lie in a specific niche that allows them to remain inactive until needed, residing between the sarcolemma and basal membrane of muscle cells (myofibrils). One side of the cell is attached to the basal membrane by two factors. First, the satellite cell has a layer of integrin alpha7beta1 which lies on the side where growth factors and inhibitors from the vasculature, autocrine and motor neuron systems can be received to signal an active or inactive state. Anchoring the satellite cell and its layer of integrin to the basal membrane are laminin, creating a selectively permeable membrane. On the opposite side where the satellite cell resides in a small recess on the myofibril, the satellite cell is attached to the sarcolemma by M-cadherine. On the myofibril side the satellite cell receives signals from the immune system and the myocyte nucleus. The location of SCs allows signals to be sent from multiple systems, such as Hepatocyte growth factor (HGF), which is secreted from the Extracellular Matrix (ECM). (Kralaki, Fili, Philippou Koutserilieris. 2009). Satellite cell structure is somewhat unique because for the most part of their existence in a healthy body they are quiescent or inactive. Because of their mostly dormant stages they have few organelles and an abundance of cytoplasm (Kralaki, Fili, Philippou Koutserilieris. 2009). Also noted is the higher concentration of satellite cells near neuromuscular junctions (NMJ) as well as a higher concentration near slow twitch muscle fibers compared to fast twitch fibers. The reason for these concentrations is currently unknown. Lastly, muscle cell concentration dramatically decreases after birth and decreases further through age. In mice it was shown that after birth satellite cells accounted for 30% of sublaminar muscle nuclei and at the age of 2 months that number has shrunk to less than 5%, showing that satellite cells play in important role in early generation of muscles and limbs (Kuang, Gillespie Rudnicki, 2012). Sub Point: Satellite Cells are activated by growth factors (MGFs) when muscles are damaged. There are many systems known and suspected of influencing SC activation and deactivation. Some include the vascular system, the immune system, the neuromuscular system, the autocrine system, and finally the myocyte nucleus. Most of the activation is influenced by the immune system after a muscle cell has been damaged. Once traumatized, Necrophils and Macrophages of the immune system migrate to the site of damage and phagocyte the damaged muscle cell material while releasing growth factors to activate quiescent SCs. At the same time the growth factors stored in the extra cellular matrix, vascular systems, and myocyte nuclei are also released after muscle injury. Examples of the growth factors released by all of these systems are HGF, IGF-1, and IGF-2. These factors bind to satellite cells and initiate SC migration to the damaged cite and start the mitotic cell cycle. Research regarding migration of satellite cells to damaged sites is in its early stages of understanding, what seems to be agreed upon is that factors released from the ECM, immune system, and muscle cells affect the migration of SCs to damaged sites. One factor, TGF-beta, which is released by the immune system is thought to directly attract satellite cells to damaged areas as experiments with a TGF-beta antibody extract reduced SC migration (Griffin, 2009). Activated SCs express MyoD and Myf5 (Broek, Gregte Hoff, 2010). The up regulation of these two factors is evident in every initially activated SC. There are more than 20 different chemo reactants being studied that are known to somehow affect SC migration (Griffin, 2009). Sub Point: SCs proliferate and rebuild at the site of damaged myofibrils. a. SC enter the cell cycle when activated, creating both unspecified stem cells and myofiber specific cells which fuse with existing cells to bridge and fill the damaged area. (Ciciliot Schiaffino, 2010) b. M-cadherin attaches SCs to a myofiber, which is crucial for cell-to-cell fusion and proliferation c. 8 key growth factors are known to stimulate and inhibit the processes of muscle cell regeneration. (Broek, Gregte Hoff, 2010) Conclusion: Current research has yielded information about the regulatory proteins and hormones that trigger satellite cells and immune responses to either inhibit or activate muscle hypertrophy. The knowledge associated with what turns on and off specific systems of muscle cell activity advances medical solutions to muscle atrophy and recreational solutions to body building and general muscle health. Future research could yield treatments that alleviate various diseases associated with muscle failure and degeneration as well as advancements in sports medicine and injury rehabilitation.