Abstract
Muscle dysfunction, characterized by a reductive remodeling of muscle fibers, is a common systemic manifestation in highly prevalent conditions such as chronic heart failure (CHF), chronic obstructive pulmonary disease (COPD), cancer cachexia, and critically ill patients. Skeletal muscle dysfunction and impaired muscle mass may predict morbidity and mortality in patients with chronic diseases, regardless of the underlying condition. High levels of oxidants may alter function and structure of key cellular molecules such as proteins, DNA, and lipids, leading to cellular injury and death. Protein oxidation including protein carbonylation was demonstrated to modify enzyme activity and DNA binding of transcription factors, while also rendering proteins more prone to proteolytic degradation. Given the relevance of protein oxidation in the pathophysiology of many chronic conditions and their comorbidities, the current review focuses on the analysis of different studies in which the biological and clinical significance of the modifications induced by reactive carbonyls on proteins have been explored so far in skeletal muscles of patients and animal models of chronic conditions such as COPD, disuse muscle atrophy, cancer cachexia, sepsis, and physiological aging. Future research will elucidate the specific impact and sites of reactive carbonyls on muscle protein content and function in human conditions.
Highlights
Muscle dysfunction, in which muscle fibers undergo a reductive remodeling, is a common systemic manifestation in highly prevalent conditions such as chronic heart failure (CHF), chronic obstructive pulmonary disease (COPD), cancer cachexia, and critically ill patients
In another recent study from our group, patients with cachexia associated with two different respiratory conditions, lung cancer or COPD, exhibited an increase in total protein carbonylation in the vastus lateralis and blood compartments compared to the healthy control subjects
Especially protein oxidation, induces modifications on key proteins involved in muscle contraction, metabolism and structure, which may alter the function of the target muscles
Summary
In which muscle fibers undergo a reductive remodeling, is a common systemic manifestation in highly prevalent conditions such as chronic heart failure (CHF), chronic obstructive pulmonary disease (COPD), cancer cachexia, and critically ill patients. High levels of oxidants may alter the function and structure of key a key contributing factor to the respiratory and limb muscle dysfunction of patients with COPD [14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30], cellular molecules as proteins, DNA,cancer and lipids, leading to cellular injury and cell muscles ofsuch animals with experimental cachexia eventually [31,32,33], and sepsis [34,35,36,37,38,39,40], and in elderly subjects [41,42,43].
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