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Abstract <p>Mechanical unloading of postural muscles (elimination of loadand afferent support stimulus) leads to a deterioration of musclefunction, i.e., muscle weakness. Excessive accumulation of reactiveoxygen species (ROS) in muscles is known to entail a decrease intheir strength and an increase in fatigability. Several differentsources of ROS are known in muscle tissue, whose regulatory effectshave both common and distinct targets. It is also known that ROS-regulatedchanges in calcium content in the myoplasm and mitochondria playa key role in muscle contraction. In muscle fibers, there are twomain ROS sources: the mitochondrial electron transport chain andNADPH oxidase-2 (NOX2). The role of different ROS sources in theregulation of signaling processes and muscle functions under mechanical unloadinghas not been studied previously. In this regard, the aim of ourwork was to study the effect of NOX2-dependent and mitochondrialROS on calcium-dependent signaling processes and strength characteristicsof 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 wasa group with daily intraperitoneal administration of mito-TEMPO,a superoxide dismutase mimetic accumulating in mitochondria. In thesecond experiment, a group of suspended animals was daily administeredthe indirect NOX2 inhibitor losartan for 7 days. Both drugs partially preventedthe increased fatigue of the soleus muscle after 7-day suspension;however, the decline in maximum contraction force was preventedonly in the losartan-treated group. Prevention of myoplasmic calciumaccumulation and calcium-dependent degradation of the electromechanicalcoupling protein junctophilin-1 was also observed only in the losartan-treatedgroup, whereas mitochondrial calcium was but slightly reduced inboth treatment groups. Thus, NOX2-dependent (but not mitochondrial) ROScontribute to myoplasmic calcium accumulation under mechanical unloading,which in turn regulates maximum contraction force under these conditions;meanwhile, both mitochondrial and NOX2-dependent ROS contributeto the increase in fatigue during mechanical unloading.</p>

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Differential Regulation of Soleus Muscle Functions by NOX-Dependent and Mitochondrial Reactive Oxygen Species under Conditions of 7-Day Mechanical Unloading

  • 期刊论文

  • 发表日期：

    2026年4月19日

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  • D. A. Sidorenko,
  • S. A. Tyganov,
  • I. D. Lvova,
  • A. A. Kulishenko,
  • B. S. Shenkman,
  • K. A. Sharlo

摘要

Abstract

Mechanical unloading of postural muscles (elimination of loadand afferent support stimulus) leads to a deterioration of musclefunction, i.e., muscle weakness. Excessive accumulation of reactiveoxygen species (ROS) in muscles is known to entail a decrease intheir strength and an increase in fatigability. Several differentsources of ROS are known in muscle tissue, whose regulatory effectshave both common and distinct targets. It is also known that ROS-regulatedchanges in calcium content in the myoplasm and mitochondria playa key role in muscle contraction. In muscle fibers, there are twomain ROS sources: the mitochondrial electron transport chain andNADPH oxidase-2 (NOX2). The role of different ROS sources in theregulation of signaling processes and muscle functions under mechanical unloadinghas not been studied previously. In this regard, the aim of ourwork was to study the effect of NOX2-dependent and mitochondrialROS on calcium-dependent signaling processes and strength characteristicsof 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 wasa group with daily intraperitoneal administration of mito-TEMPO,a superoxide dismutase mimetic accumulating in mitochondria. In thesecond experiment, a group of suspended animals was daily administeredthe indirect NOX2 inhibitor losartan for 7 days. Both drugs partially preventedthe increased fatigue of the soleus muscle after 7-day suspension;however, the decline in maximum contraction force was preventedonly in the losartan-treated group. Prevention of myoplasmic calciumaccumulation and calcium-dependent degradation of the electromechanicalcoupling protein junctophilin-1 was also observed only in the losartan-treatedgroup, whereas mitochondrial calcium was but slightly reduced inboth treatment groups. Thus, NOX2-dependent (but not mitochondrial) ROScontribute to myoplasmic calcium accumulation under mechanical unloading,which in turn regulates maximum contraction force under these conditions;meanwhile, both mitochondrial and NOX2-dependent ROS contributeto the increase in fatigue during mechanical unloading.