Desmin Degradation in Skeletal Muscles of Patients with Chronic Critical Illness

• Published in: Journal of evolutionary biochemistry and physiology Vol. 59; no. 6; pp. 2381 - 2389
• Main Authors: Tyganov, S. A., Zaripova, K. A., Turtikova, O. S., Skiteva, E. N., Belova, S. P., Zabrodskaya, Yu. M., Kondratiev, S. A., Kondratieva, E. A., Kondratiev, A. N., Shenkman, B. S.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01.11.2023; Springer Nature B.V
• Subjects: Animal Physiology; Biochemistry; Biomedical and Life Sciences; Biopsy; Calpain; Cytoskeleton; Degradation; Depolymerization; Desmin; Evolutionary Biology; Experimental Papers; Filaments; Illnesses; Life Sciences; Medical research; mRNA; Myopathy; Neurosurgery; Patients; Phosphorylation; Proteasomes; Skeletal muscle; Soleus muscle; Ubiquitin-protein ligase; chronic critical illness; desmin; ubiquitin ligases; skeletal muscle; chronic disorder of consciousness; proteolysis; critical illness myopathy
• ISSN: 0022-0930; 1608-3202
• DOI: 10.1134/S0022093023060388

Patients with chronic critical illness lose a considerable portion of their muscle mass while hospitalized in an intensive care unit, which can have long-term detrimental effects. Among other factors, this leads to a disintegration of muscle cytoskeleton, and currently there are no comprehensive studies describing the mechanisms behind the development of this pathology. Here, we aimed to investigate the signaling processes that contribute to desmin degradation in patients with critical illness myopathy (CIM). Incisional needle biopsies of the soleus muscle were taken from 6 patients with a chronic (≥ 2 months) disorder of consciousness, undergoing treatment at the Polenov Neurosurgical Institute (Almazov National Medical Research Center, St. Petersburg) and healthy men (control). Muscle tissue samples were frozen in liquid nitrogen for subsequent Western blot and PCR analyses, as well as immunohistochemical examination. The analysis showed that fibers with an altered histological desmin pattern were visually identified in 4 out of 6 patients. A significant decrease in desmin (by 69%) and its mRNA (by 24%) levels was observed in patients with CIM. Desmin degradation is known to occur due to increased calpain activity and activation of the ubiquitin-proteasome system. In this study, calpain-1 content increased in CIM patients at the protein level, while remaining unchanged at the mRNA level. We detected changes in GSK3-β Ser 9 -phosphorylation, which is a critical step in calpain-1-mediated depolymerization of desmin filaments. A study of ubiquitin ligases revealed a significant 155% increase in Trim32 expression paralleled by a decrease in Atrogin1 and MuRF1 expression. Thus, we observed a decrease in desmin content under CIM conditions. Desmin degradation may result from its increased GSK3β-mediated phosphorylation and subsequent calpain-1-mediated cleavage. Moreover, we found an increase in the expression of the E3 ubiquitin ligase Trim32 whose activity, according to the literature, also rises after desmin phosphorylation.