Deficiency of myostatin protects skeletal muscle cells from ischemia reperfusion injury

Tao

et al. 2022

J. Agric. Food Chem.

Neoruscogenin is a plant-origin sapogenin that has the potential to modulate muscle growth among the smallmolecule compounds that we previously predicted by artificial intelligence to target myostatin (MSTN). This study aimed to elucidate the biological role of neoruscogenin on muscle growth and its relationship with MSTN. Using molecular biological techniques, we found that neoruscogenin inhibited MSTN maturation, thereby repressing its signal transduction; further facilitated protein synthesis metabolism and reduced protein degradation metabolism, ultimately promoting the differentiation of myoblasts and hypertrophy of muscle fibers; and had the effect of repairing muscle injury. This study enriched the biological functions of neoruscogenin and provided a theoretical basis for the treatment of human myopathy and its application in the livestock industry.

Section: ■ Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 94%

Novel Pro-myogenic Factor Neoruscogenin Induces Muscle Fiber Hypertrophy by Inhibiting MSTN Maturation and Activating the Akt/mTOR Pathway

Tao

et al. 2022

J. Agric. Food Chem.

“…The IL-6/JAK-STAT pathway is required for myogenic cell proliferation and differentiation and is known to depend on and respond to upstream stimuli. 11,25,36,38 In the presence of a high dose of LPS, although there were significant increases in the expression levels of target factors examined compared with the expression levels in the no-intervention group of cells, the expression levels of IL-6, Pax7, myostatin, HO-1, eNOS, and HSP90 were similar in the control and LIPUS groups. On the other hand, myostatin expression was decreased by LIPUS, while LIPUS did not alter myogenin expression.…”

Section: Discussionmentioning

confidence: 94%

Therapeutic Myogenesis Induced by Ultrasound Exposure in a Volumetric Skeletal Muscle Loss Injury Model

Mohamad Yusoff,

Nakashima,

Kajikawa

et al. 2023

Am J Sports Med

Background: Low-intensity pulsed ultrasound (LIPUS) irradiation has been shown to induce various responses in different cells. It has been shown that LIPUS activates extracellular signal–regulated kinase 1/2 (ERK1/2) through integrin. Purpose: To study the effects of LIPUS on myogenic regulatory factors and other related myogenesis elements in a volumetric skeletal muscle loss injury model. Study Design: Controlled laboratory study. Methods: C57BL/6J mice were subjected to full-thickness muscle defect injury of the quadriceps and treated with direct application of LIPUS 20 min/d or non-LIPUS treatment (control) for 3, 7, and 14 days. LIPUS was also applied to C2C12 cells in culture in the presence of low and high doses of lipopolysaccharides. The expression levels of myogenic regulatory factors and the expression levels of myokine-related and angiogenic-related proteins of the control and LIPUS groups were analyzed. Results: Muscle volume in the injury site was restored at day 14 with LIPUS treatment. Paired-box protein 7, myogenic factor 5, myogenin, and desmin expressions were significantly different between control and LIPUS groups at days 7 and 14. Myokine and angiogenic cytokine-related factors were significantly increased in the LIPUS group at day 3 and decreased with no significant difference between the groups by day 14. LIPUS induced different responses of myogenic regulatory factors in C2C12 cells with low and high doses of lipopolysaccharides. LIPUS promoted myogenesis through short-lived increase in interleukin-6 and heme oxygenase 1, together with activation of ERK1/2. Conclusion: LIPUS had a constant effect on the variables of tissue damage, from macrotrauma to microtrauma, leading to efficient muscle regeneration. Clinical Relevance: The focus of therapeutic strategies with LIPUS has been not only for microvascular regeneration but also for skeletal muscle and related local tissue recovery from acute or chronic damage.

“…Expression levels of proteins were determined densitometrically using Fiji software after subtracting the background signal. Protein levels were corrected with the positive control and expressed as relative values compared with the T/HS vehicle–pretreated group (48).…”

Section: Methodsmentioning

confidence: 99%

A2A Adenosine Receptors Regulate Multiple Organ Failure After Hemorrhagic Shock in Mice

Keleştemur

Németh

Pacher

et al. 2022

Shock

Trauma hemorrhagic shock (T/HS) is a clinical condition that causes multiple organ failure that needs rapid intervention. Restricted oxygen at the cellular level causes inflammation and subsequent cell death. Adenosine triphosphate is the universal intracellular energy currency and an important extracellular inflammatory signaling molecule. Adenosine, an endogenous nucleotide formed as a result of the breakdown of adenosine triphosphate, is also released during T/HS. Adenosine binds to four G protein–coupled receptors (A1R, A2a, A2b, A3R) called adenosine receptors or P1 receptors. In the present study, we evaluated the effect of activation, inactivation, and genetic absence of A2aR (A2aR−/− mice) on T/HS-induced multiple organ failure. Wild-type mice were pretreated (30 min before shock induction) with an agonist or antagonist and then subjected to T/HS by withdrawing arterial blood and maintaining the blood pressure between 28 and 32 mm Hg. A2aR−/− mice were subjected to T/HS in the absence of pharmacologic treatment. Neutrophil sequestration was assessed by detecting myeloperoxidase, and Evans blue dye (EBD) method was used to analyze lung permeability. Blood and lung inflammatory cytokine levels were determined by sandwich enzyme-linked immunosorbent assay. The liver enzymes aspartate aminotransferase and alanine aminotransferase were determined spectrophotometrically from plasma. Activation of the apoptotic cascade was evaluated using a mouse apoptosis array. Our results demonstrate that the selective A2aR agonist CGS21680 decreases lung neutrophil sequestration, lung proinflammatory cytokines IL-6 and TNF-α, and bronchoalveolar lavage EBD. Pretreatment with the selective antagonist ZM241385 and genetic blockade in A2aR−/− mice increased neutrophil sequestration, proinflammatory cytokine levels, and bronchoalveolar lavage fluid EBD. The myeloperoxidase level in the lung was also increased in A2aR−/− mice. We observed that antiapoptotic markers decreased significantly with the absence of A2aR in the lung and spleen after T/HS. In conclusion, our data demonstrate that activation of A2aR regulates organ injury and apoptosis in the setting of T/HS.