Abstract: Mechanical unloading of postural muscles (elimination of load and afferent support stimulus) leads to a deterioration of muscle function, i.e., muscle weakness. Excessive accumulation of reactive oxygen species (ROS) in muscles is known to entail a decrease in their strength and an increase in fatigability. Several different sources of ROS are known in muscle tissue, whose regulatory effects have both common and distinct targets. It is also known that ROS-regulated changes in calcium content in the myoplasm and mitochondria play a key role in muscle contraction. In muscle fibers, there are two main ROS sources: the mitochondrial electron transport chain and NADPH oxidase-2 (NOX2). The role of different ROS sources in the regulation of signaling processes and muscle functions under mechanical unloading has not been studied previously. In this regard, the aim of our work was to study the effect of NOX2-dependent and mitochondrial ROS on calcium-dependent signaling processes and strength characteristics of the soleus muscle under conditions of 7-day mechanical unloading. Two experiments were conducted with 7-day hindlimb suspension of rats. In one of them, in addition to a 7-day placebo group, there was a group with daily intraperitoneal administration of mito-TEMPO, a superoxide dismutase mimetic accumulating in mitochondria. In the second experiment, a group of suspended animals was daily administered the indirect NOX2 inhibitor losartan for 7 days. Both drugs partially prevented the increased fatigue of the soleus muscle after 7-day suspension; however, the decline in maximum contraction force was prevented only in the losartan-treated group. Prevention of myoplasmic calcium accumulation and calcium-dependent degradation of the electromechanical coupling protein junctophilin-1 was also observed only in the losartan-treated group, whereas mitochondrial calcium was but slightly reduced in both treatment groups. Thus, NOX2-dependent (but not mitochondrial) ROS contribute to myoplasmic calcium accumulation under mechanical unloading, which in turn regulates maximum contraction force under these conditions; meanwhile, both mitochondrial and NOX2-dependent ROS contribute to the increase in fatigue during mechanical unloading

Cite: Sidorenko D.A. , Tyganov S.A. , Lvova I.D. , Kulishenko A.A. , Shenkman B.S. , Sharlo K.A.
Differential Regulation of Soleus Muscle Functions by NOXDependent and Mitochondrial Reactive Oxygen Species under Conditions of 7-Day Mechanical Unloading
Journal of Evolutionary Biochemistry and Physiology. 2026. V.62. N2. P.564-580. DOI: 10.1134/S1990747826700091 OpenAlex

Dates:

Submitted:	Feb 24, 2026
Accepted:	Mar 26, 2026

Identifiers:

OpenAlex:

W7161803414

Citing: Пока нет цитирований

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