P38α-MAPK Signaling Inhibition Attenuates Soleus Atrophy during Early Stages of Muscle Unloading

Belova, Svetlana P.; Mochalova, Ekaterina P.; Kostrominova, Tatiana Y.; Шенкман, Борис; Nemirovskaya, T. L.

doi:10.3390/ijms21082756

Cited by 13 publications

(10 citation statements)

References 48 publications

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“…It was previously reported that the expression of E3 ubiquitin ligases MAFbx and MuRF1 is increased after three days of unloading [15]. In the current study, the mRNA expression of MAFbx and MuRF1 was also significantly increased by unloading ( Figure 3).…”

Section: Effect Of Hdac Inhibitors On Skeletal Muscle Atrophysupporting

confidence: 76%

Differences in the Role of HDACs 4 and 5 in the Modulation of Processes Regulating MAFbx and MuRF1 Expression during Muscle Unloading

Mochalova

Belova

Kostrominova

et al. 2020

IJMS

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Unloading leads to skeletal muscle atrophy via the upregulation of MuRF-1 and MAFbx E3-ligases expression. Reportedly, histone deacetylases (HDACs) 4 and 5 may regulate the expression of MuRF1 and MAFbx. To examine the HDAC-dependent mechanisms involved in the control of E3-ubiquitin ligases expression at the early stages of muscle unloading we used HDACs 4 and 5 inhibitor LMK-235 and HDAC 4 inhibitor Tasqinimod (Tq). Male Wistar rats were divided into four groups (eight rats per group): nontreated control (C), three days of unloading/hindlimb suspension (HS) and three days HS with HDACs inhibitor LMK-235 (HSLMK) or Tq (HSTq). Treatment with LMK-235 diminished unloading-induced of MAFbx, myogenin (MYOG), ubiquitin and calpain-1 mRNA expression (p < 0.05). Tq administration had no effect on the expression of E3-ligases. The mRNA expression of MuRF1 and MAFbx was significantly increased in both HS and HSTq groups (1.5 and 4.0 folds, respectively; p < 0.05) when compared with the C group. It is concluded that during three days of muscle unloading: (1) the HDACs 4 and 5 participate in the regulation of MAFbx expression as well as the expression of MYOG, ubiquitin and calpain-1; (2) the inhibition of HDAC 4 has no effect on MAFbx expression. Therefore, HDAC 5 is perhaps more important for the regulation of MAFbx expression than HDAC 4.

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Section: Effect Of Hdac Inhibitors On Skeletal Muscle Atrophysupporting

confidence: 76%

Differences in the Role of HDACs 4 and 5 in the Modulation of Processes Regulating MAFbx and MuRF1 Expression during Muscle Unloading

Mochalova

Belova

Kostrominova

et al. 2020

IJMS

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“…Recent work showed that MuRF1-KO protected both the tibialis anterior and soleus muscles from monocrotaline injection, indicating a similar importance of MuRF1 for both muscles regarding mass, fiber cross sectional areas, and force depletion [35]. In addition, numerous studies described an over-expression of MuRF1 in soleus muscle upon various atrophy situations [35,[100][101][102][103].…”

Section: Tissue/fibrillar Locationmentioning

confidence: 99%

MuRF1/TRIM63, Master Regulator of Muscle Mass

Peris-Moreno

Taillandier

Polge

2020

IJMS

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The E3 ubiquitin ligase MuRF1/TRIM63 was identified 20 years ago and suspected to play important roles during skeletal muscle atrophy. Since then, numerous studies have been conducted to decipher the roles, molecular mechanisms and regulation of this enzyme. This revealed that MuRF1 is an important player in the skeletal muscle atrophy process occurring during catabolic states, making MuRF1 a prime candidate for pharmacological treatments against muscle wasting. Indeed, muscle wasting is an associated event of several diseases (e.g., cancer, sepsis, diabetes, renal failure, etc.) and negatively impacts the prognosis of patients, which has stimulated the search for MuRF1 inhibitory molecules. However, studies on MuRF1 cardiac functions revealed that MuRF1 is also cardioprotective, revealing a yin and yang role of MuRF1, being detrimental in skeletal muscle and beneficial in the heart. This review discusses data obtained on MuRF1, both in skeletal and cardiac muscles, over the past 20 years, regarding the structure, the regulation, the location and the different functions identified, and the first inhibitors reported, and aim to draw the picture of what is known about MuRF1. The review also discusses important MuRF1 characteristics to consider for the design of future drugs to maintain skeletal muscle mass in patients with different pathologies.

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“…Other 2-AR agonists like espindolol have also been shown to ameliorate muscle loss and to blunt E3 ligase expression in aged rats. The authors found that both NF-κB and myostatin expression was reduced with no effect on AKT and FOXO3a [ 292 ]. Altogether, this strongly suggests that the positive effects of 2-AR agonists on muscle mass are mediated through the modulation of different signaling pathways depending on the catabolic stimuli, which complicates future therapeutical strategies.…”

Section: Current Treatments/potential Modes Of Actionmentioning

confidence: 99%

Ubiquitin Ligases at the Heart of Skeletal Muscle Atrophy Control

et al. 2021

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Skeletal muscle loss is a detrimental side-effect of numerous chronic diseases that dramatically increases mortality and morbidity. The alteration of protein homeostasis is generally due to increased protein breakdown while, protein synthesis may also be down-regulated. The ubiquitin proteasome system (UPS) is a master regulator of skeletal muscle that impacts muscle contractile properties and metabolism through multiple levers like signaling pathways, contractile apparatus degradation, etc. Among the different actors of the UPS, the E3 ubiquitin ligases specifically target key proteins for either degradation or activity modulation, thus controlling both pro-anabolic or pro-catabolic factors. The atrogenes MuRF1/TRIM63 and MAFbx/Atrogin-1 encode for key E3 ligases that target contractile proteins and key actors of protein synthesis respectively. However, several other E3 ligases are involved upstream in the atrophy program, from signal transduction control to modulation of energy balance. Controlling E3 ligases activity is thus a tempting approach for preserving muscle mass. While indirect modulation of E3 ligases may prove beneficial in some situations of muscle atrophy, some drugs directly inhibiting their activity have started to appear. This review summarizes the main signaling pathways involved in muscle atrophy and the E3 ligases implicated, but also the molecules potentially usable for future therapies.

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P38α-MAPK Signaling Inhibition Attenuates Soleus Atrophy during Early Stages of Muscle Unloading

Cited by 13 publications

References 48 publications

Differences in the Role of HDACs 4 and 5 in the Modulation of Processes Regulating MAFbx and MuRF1 Expression during Muscle Unloading

Differences in the Role of HDACs 4 and 5 in the Modulation of Processes Regulating MAFbx and MuRF1 Expression during Muscle Unloading

MuRF1/TRIM63, Master Regulator of Muscle Mass

Ubiquitin Ligases at the Heart of Skeletal Muscle Atrophy Control

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