Journal of Muscle Research and Cell Motility最新文献

The integrated stress response (ISR) and mitochondrial unfolded protein response (UPR^mt) plays a vital role in myogenic differentiation of muscle satellite cells. In this study, chronic ISR and UPR^mt was induced with impaired myogenic differentiation and cluster of differentiation 36 (CD36) was highly expressed and localized on the mitochondria in aging muscle. Little is known about the interplay of CD36 and ISR during differentiation. Knocking down CD36 expression at day 3 in differentiated C2C12 myoblasts indicated that the expression levels of Activating transcription factor 4 (ATF4), and other ISR - related proteins decreased, but the expression levels of UPR^mt - related proteins Activating transcription factor 5 (ATF5), Heat Shock Protein 60(HSP60) and Heat Shock Protein 10(HSP10) increased with mRNA level of HSP60 increased. Meanwhile Myogenin (MyoG) expression level was increased but Myosin heavy chain 1 (Myh1) expression level was decreased. Following CD36 knockdown, mito-nuclear protein imbalance and mitochondrial dysfunction occurred. Interaction between CD36 and Mammalian Target of Rapamycin (mTOR) was observed in aging muscle. Collectively, CD36 was localized on the mitochondria in aging muscle, while CD36 was associated with ISR and UPR^mt early during myogenic differentiation in C2C12 myoblasts, which could have implications for the development of new strategies to treat sarcopenia.

S-ketamine is recognized as a rapid-acting antidepressant, exerting its effects primarily through activation of the mTOR signaling pathway in the brain, which plays a key role in neuroplasticity. Given the shared molecular mechanisms between brain and skeletal muscle, we investigated whether S-ketamine can also modulate regulatory proteins involved in muscle protein synthesis (MPS) and muscle protein breakdown (MPB) in skeletal muscle. Adult female Flinders Sensitive Line rats received a single intraperitoneal injection of S-ketamine (20 mg/kg) or saline, and soleus and extensor digitorum longus (EDL) muscles were collected two hours post-injection for protein analysis using Western blot. S-ketamine significantly increased phosphorylated mTOR (p-mTOR^Ser2448) in both soleus and EDL, while total ULK1 protein expression was elevated in soleus. These findings suggest that S-ketamine can stimulate mTOR-related signaling in skeletal muscle, potentially enhancing MPS, although the activation was limited to specific signaling proteins. The results provide novel insights into the peripheral effects of S-ketamine beyond the central nervous system, highlighting the potential relevance for skeletal muscle physiology and anabolic regulation. Future studies are warranted to determine the temporal dynamics of these effects, the dose-dependence, and the impact of repeated administration on muscle hypertrophy. Overall, this study expands understanding of S-ketamine's systemic actions and raises new questions regarding its potential as a modulator of skeletal muscle protein metabolism.

Polystyrene microplastic (PS-MP), known as a white pollutant, exhibited adverse effects on aquatic and terrestrial animals. The present study aims to evaluate the dose-dependent effect of polystyrene microplastics on skeletal muscle energy metabolism in Wistar rats. PS-MP was administered orally in Wistar rats at doses of 0.5 mg/L, 5 mg/L, and 50 mg/L in drinking water for 28 days daily. After the treatment, metabolic profile and tissue histological analyses were performed. Average food consumption by the treated rats was decreased by PS-MPs. Glycogen and pyruvate contents were depleted in a dose-responsive fashion. Lactate dehydrogenase and transaminase activities were decreased by PS-MP exposure. Free amino nitrogen was mobilized from blood to skeletal muscle in response to stress. Protein content depleted in the muscular tissue whereas enhanced carbonylated protein formation. Pronase and cathepsin activities were increased by PS-MP. Inhibited TCA cycle enzyme activities were observed in the target tissue. Moreover, muscle hypertrophy, nuclear migration, and fibrillation were seen in histological sections. Decreased food consumption by PS-MP exposure could promote glucose scarcity in blood. Depletion of muscular glycogen may result from increased glycogenolysis to replenish loss of blood glucose. Reduction in pyruvate content may result from decreased glycolysis which could perturb the lactate dehydrogenase function. Lack of transaminase in the target tissue was indicative of tissue damage. Muscular protein breakdown might be due to oxidative denaturation of native proteins as well as increased proteolysis. Due to less pyruvate production, the TCA cycle enzyme functions were suppressed. Histopathological studies established significant degenerative changes in muscular morphology following PS-MP exposure. The present study suggests that PS-MP perturbed skeleto-muscular energy metabolism and promoted muscle fiber degeneration following sub-acute exposure.

A brief discussion about skeletal muscle, aberrant expression of dystrophin from null mutations of the gene, potential explanations as to why this occurs, and how understanding this could be useful for potential therapies in the future.

Human gastric motility is regulated by both slow wave activity and membrane excitability. Regulation of gastric function involves adapting motility through repetitive stretches during feeding and digestion. Alongside gastric motility, gastric vascular motility must also be accurately regulated. The physiological function of stretch-activated K⁺ channels has been demonstrated in the relaxation mechanisms of the uterus and bladder. For these reasons, this study was designed to investigate whether stretch-activated K⁺ channels are involved in the functional regulation of human gastric muscle and vessels. We examined human gastric body tissues and gastroepiploic arteries from patients who underwent gastrectomy using a conventional contractile measurement system and Western immunoblot. High concentrations of K⁺ (50 mM) induced tonic contraction (4 g) in human gastric circular muscle from the body. Acetylcholine (ACh, 10 µM) also induced an initial peak (3 g), tonic (1.1 g), and phasic contractions (1.5 g; 2.5 cycles/min). L-methionine, known to block TWIK (two-pore domain weak inward rectifying K_2P channel)-related K⁺ channels (TREK-1), produced sustained contraction (2 g) in gastric smooth muscle in the presence of a cocktail of K⁺ channel blockers. Additionally, channel inhibitors such as extracellular acidosis (MES ([pH]_o = 6.4)), quinidine, bupivacaine, and lidocaine enhanced spontaneous contractions by 224%, 183%, 138%, and 127% of control, respectively, in the presence of L-methionine. Concurrently, we analyzed the physiological role of TREK-1 and TASK-2 in the human gastroepiploic artery. The ring of the human gastroepiploic artery produced tonic contraction (2.8 g) under high K⁺ (50 mM). Following stimulation with high K⁺, the artery exhibited spontaneous vasoconstriction known as vasomotion (2.7 g; 0.13 cycles/min), which was completely inhibited by nifedipine, a voltage-dependent L-type Ca²⁺ channel (VDCC_L) blocker. BayK 8644, an activator of VDCC_L, induced vasomotion, which was also inhibited by nifedipine. In the human artery, L-methionine induced a vascular tonic contraction (0.15 g) and enhanced vasomotion by 179%. Additionally, lidocaine induced peak and tonic contractions of 1 g and 0.7 g, respectively. Both L-methionine and lidocaine also enhanced vasomotion induced by BayK 8644. The molecular presence of TREK-1 and TASK-2 was confirmed via Western blot in human gastric muscle, gastric mucosa, and artery, respectively. These findings suggest that TREK-1 and TASK-2 may be significant regulators of human gastric muscle and vascular motility.

Microtubule acetylation is known to promote autophagic degradation; however, its therapeutic potential in resolving exercise-induced autophagic flux blockage and facilitating injured muscle recovery remains unclear. In this study, Sprague-Dawley rats were treated with Tubastatin A for 3 consecutive days to enhance microtubule acetylation. Subsequently, the rats underwent a 90-minute downhill run at a gradient of -16°and a speed of 16 m·min⁻¹. Soleus muscles were sampled at 12 h post-exercise. Single muscle fibers were isolated and labelled with α-tubulin, acetylated α-tubulin (AcK40 α-tubulin), cytoplasmic dynein intermediate chain (dynein), or LC3 for immunofluorescent analysis. Protein expression of α-tubulin, AcK40 α-tubulin, dynein, LC3, p62, Myf5, Myod, and Myogenin were detected by Western blot. The results showed that Tubastatin A treatment significantly upregulated the expression of AcK40 α-tubulin and dynein. It also increased the amount of dynein on α-tubulin and promoted the retrograde transport of autophagosomes. In response to downhill running, Tubastatin A-treated rats exhibited enhanced autolysosome formation, along with reduced LC3-II and p62 expression. Additionally, Tubastatin A further potentiated the increases in MyoD and Myogenin induced by downhill running. These findings suggest that enhancing microtubule acetylation through Tubastatin A can mitigate the impairment of autophagosome degradation caused by downhill running and promote the myogenic program in skeletal muscle.

The aim of this study was to determine the impact of myostatin deficiency on the mechanical and contractile adaptations of the soleus muscle to functional overload (FO). Using a cross-sectional design, we compared the control and FO soleus muscles of myostatin-deficient (BEH^cc) and myostatin-functional (BEH⁺⁺) mice. FO was induced by 28 days of gastrocnemius ablation. Soleus muscles were isolated and subjected to an isometric-eccentric contraction protocol to analyse contractile performance and tissue mechanical behaviour. FO significantly increased muscle mass, tetanic force, and stiffness, in BEH⁺⁺ mice (p < 0.05), but not in BEH^cc where absolute force was even reduced (p < 0.05). These findings indicate that myostatin plays an important role in successful skeletal muscle adaptations and preservation of muscle function under chronic loading.

Vascular smooth muscle cells (SMC) comprise the medial layer of blood vessels and are responsible for maintaining vascular tone. Ordinarily quiescent and contractile, SMC can dedifferentiate into different phenotypes following injury or in disease states such as atherosclerosis and are thus valuable research tools for examining these conditions. The isolation of commonly used SMC types, such as those from the aorta or saphenous vein (SV), require clinical links or commercial supply and are rarely pathology-free. The skin is highly vascularised with perforator (Perf) vessels that protrude through the skin layers to feed the tissue. Whilst these vessels can be sourced from clinical procedures (e.g. reconstructive surgery), they are also available from elective cosmetic procedures such as abdominoplasty which could provide blood vessels unaffected by an underlying pathology. This paper describes the isolation of Perf-SMC for the first time, using a cost-effective explant technique. Explanted cells were confirmed as SMC by co-staining for alpha smooth muscle actin and smooth muscle myosin heavy chain. Phenotypic characteristics of Perf-SMC (cell morphology, proliferation, and multinucleation) were comparable to those from commonly used SMC from alternative vascular sources (SV-SMC and umbilical artery SMC). Furthermore, Perf-SMC were stable in culture up until at least passage 9 with no alteration in morphological characteristics or evidence of replication-induced phenotypic change. In summary, this paper describes an effective, efficient and low-cost method for isolating SMC from skin perforator vessels that may be a useful tool for the future examination of SMC behaviour from both pathological and healthy skin.