Desmin Phosphorylation in human skeletal muscle can be modified by Resistance Exercise rendering the protein less vulnerable to protease-dependent cleavage

Abstract

Abstract The desmin intermediate filament (IF) system plays a crucial role in stress transmission, mechano-protection, and the regulation of signaling in skeletal muscle. Loss of IF integrity is considered a triggering factor for myofibril breakdown and muscle atrophy. Phosphorylation of desmin (pDes) has been identified as a priming factor leading to an organized process provoking muscle atrophy. Intervening in pDes has been suggested as a promising method to counteract the loss of muscle mass. Physical exercise stands out as a prominent and non-pharmacological option for purposefully modifying cellular signaling to promote muscle health and function. To investigate whether resistance exercise (RE) specifically influences the regulation of pDes, 10 healthy young men (n=7) and women (n=3) performed 7 weeks of RE training (14 sessions; 2 per week). Muscle biopsies were collected in both untrained and trained conditions at rest (pre 1, pre 14) and one hour after RE (post 1, post 14). Desmin content and phosphorylation at serine 31 and 60 (pDesS31, pDesS60) as well as threonine 17 and 76/77 (pDesT17, pDesT76/77) were analyzed. In untrained condition (pre 1, post 1), acute RE resulted in the dephosphorylation of S31 (p < 0.001) and S60 (p < 0.05). This was accompanied by reduced susceptibility of desmin in the exercised muscle to protease-induced cleavage compared to the resting state (p < 0.05). In the trained condition (pre 14, post 14), acute RE led to an augmented dephosphorylation of S31 (p < 0.01) as compared to the untrained condition (p < 0.05). Furthermore, training affected baseline phosphorylation, upregulating S31 and attenuating S60 as well as T17 while increasing total desmin content. We conclude that RE is a potent stimulus for modifying desmin phosphorylation, making the protein less prone to cleavage. Because repeated resistance training changes the phosphorylation pattern of Desmin, we introduce pDes as an adaptive mechanism of skeletal muscle, contributing to the proteostatic regulation in response to recurring stress. Focusing on underlying mechanisms and determining the most effective loading in RE-dependent induction of pDes-modification might be a promising strategy to challenge muscle atrophy in health and disease.