İskelet Kas Kütlesini Düzenleyen Moleküler Mekanizmalar

İskelet kasları plastisitesi yüksek bir dokudur. Çeşitli fizyolojik ve patolojik koşullara verdiği yanıtlardan birisi de, protein yapım veya yıkım hızında görülen değişikliklerdir. Bu çerçevede, çeşitli anabolik uyaranlar hipertrofiye yol açarken; inaktivite, denervasyon, spinal kord kesisi gibi genel olarak kullanmamaya yol açan koşullar kas atrofisine neden olur. İskelet kaslarının bir endokrin organ olarak anıldığı ve güç üretimi, hareket ve nefes alma işlevinin yanı sıra glisemik kontrol, metabolik homeostazisin sağlanması ve metabolik genlerin düzenlenmesi gibi önemli fonksiyonlara sahip olduğu düşünüldüğünde, kas kütlesinde ortaya çıkan kayıpların kan glukoz dengesini etkileyerek insulin direnci, tip 2 diyabet ve obezite gibi sorunlara neden olmakta, morbidite ve mortaliteyi artırmaktadır. Kas lifinde protein yapımı IGF1– PI3K–Akt–mTOR sinyal yolağı tarafından uyarılırken, miyostatin-Smad2/3 yolağı temel olarak protein yapımını baskılar. Diğer yandan, özellikle kullanmama atrofisinde başta ATP-bağımlı ubikütin-proteozom sistemi olmak üzere, sitozolik kalsiyum bağımlı kalpain sistemi ve lizozomal proteazlar önemli rol oynar. Protein yapımı ve yıkımını kontrol eden yolaklar kompleks bir iş birliği içerisinde çalışırlar. Böylece protein yapımının ktivasyonu, yıkımın baskılanmasını veya yıkımın uyarılması yapımın bir ölçüde azalmasını da beraberinde getirir. İskelet kas kütlesi kayıplarının önlenmesinde ve/veya geri kazandırılması için gerekli rehabilitasyon stratejilerinin geliştirilmesinde iskelet kasında protein dengesini kontrol eden moleküler mekanizmaların aydınlatılması ciddi bir önem taşımaktadır.

Molecular Mechanisms Regulating Skeletal Muscle Mass

Skeletal muscle is a plastic tissue and one of the responses to various physiological and pathological conditions is changes in protein synthesis or degradation rate. Various anabolic stimuli lead to muscle hypertrophy, while inactivity, denervation, spinal cord section, and other disuse conditions cause skeletal muscle atrophy. Today, skeletal muscles are considered as an endocrine organ and have important functions such as power production, movement, and breathing as well as glycemic control, metabolic homeostasis and regulation of metabolic genes. Therefore, loss of muscle mass affects homeostasis and leads to insulin resistance, type 2 diabetes, and obesity and results in increased morbidity and mortality. While the major anabolic pathway regulating protein synthesis in skeletal muscle is IGF1-PI3K-Akt-mTOR signaling pathway, the myostatinSmad2/3 pathway plays a major role in the suppression of protein synthesis. On the other hand, the ATP-dependent ubiquitin-proteasome system, the cytosolic calciumdependent calpain system, and lysosomal proteases play an important role in muscle atrophy. The pathways that control protein synthesis and degradation work in a coordinated fashion. Elucidating the molecular mechanisms playing role in controlling protein balance in skeletal muscle is of crucial importance to develop therapies and rehabilitation strategies for preservation of muscle tissue function.

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