Journal of Muscle Research and Cell Motility最新文献

{"title":"Mfge8 attenuates human gastric antrum smooth muscle contractions.","authors":"Wen Li,&nbsp;Ashley Olseen,&nbsp;Yeming Xie,&nbsp;Cristina Alexandru,&nbsp;Andrew Outland,&nbsp;Angela F Herrera,&nbsp;Andrew J Syder,&nbsp;Jill Wykosky,&nbsp;Brian A Perrino","doi":"10.1007/s10974-021-09604-y","DOIUrl":"https://doi.org/10.1007/s10974-021-09604-y","url":null,"abstract":"<p><p>Coordinated gastric smooth muscle contraction is critical for proper digestion and is adversely affected by a number of gastric motility disorders. In this study we report that the secreted protein Mfge8 (milk fat globule-EGF factor 8) inhibits the contractile responses of human gastric antrum muscles to cholinergic stimuli by reducing the inhibitory phosphorylation of the MYPT1 (myosin phosphatase-targeting subunit (1) subunit of MLCP (myosin light chain phosphatase), resulting in reduced LC20 (smooth muscle myosin regulatory light chain (2) phosphorylation. Mfge8 reduced the agonist-induced increase in the F-actin/G-actin ratios of β-actin and γ-actin1. We show that endogenous Mfge8 is bound to its receptor, α8β1 integrin, in human gastric antrum muscles, suggesting that human gastric antrum muscle mechanical responses are regulated by Mfge8. The regulation of gastric antrum smooth muscles by Mfge8 and α8 integrin functions as a brake on gastric antrum mechanical activities. Further studies of the role of Mfge8 and α8 integrin in regulating gastric antrum function will likely reveal additional novel aspects of gastric smooth muscle motility mechanisms.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":"42 2","pages":"219-231"},"PeriodicalIF":2.7,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10974-021-09604-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39060956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrostatic interactions in the SH1-SH2 helix of human cardiac myosin modulate the time of strong actomyosin binding.","authors":"Akhil Gargey, Shiril Bhardwaj Iragavarapu, Alexander V Grdzelishvili, Yuri E Nesmelov","doi":"10.1007/s10974-020-09588-1","DOIUrl":"10.1007/s10974-020-09588-1","url":null,"abstract":"<p><p>Two single mutations, R694N and E45Q, were introduced in the beta isoform of human cardiac myosin to remove permanent salt bridges E45:R694 and E98:R694 in the SH1-SH2 helix of the myosin head. Beta isoform-specific bridges E45:R694 and E98:R694 were discovered in the molecular dynamics simulations of the alpha and beta myosin isoforms. Alpha and beta isoforms exhibit different kinetics, ADP dissociates slower from actomyosin containing beta myosin isoform, therefore, beta myosin stays strongly bound to actin longer. We hypothesize that the electrostatic interactions in the SH1-SH2 helix modulate the affinity of ADP to actomyosin, and therefore, the time of the strong actomyosin binding. Wild type and the mutants of the myosin head construct (1-843 amino acid residues) were expressed in differentiated C₂C₁₂ cells, and the duration of the strongly bound state of actomyosin was characterized using transient kinetics spectrophotometry. All myosin constructs exhibited a fast rate of ATP binding to actomyosin and a slow rate of ADP dissociation, showing that ADP release limits the time of the strongly bound state of actomyosin. The mutant R694N showed a faster rate of ADP release from actomyosin, compared to the wild type and the E45Q mutant, thus indicating that electrostatic interactions within the SH1-SH2 helix region of human cardiac myosin modulate ADP release and thus, the duration of the strongly bound state of actomyosin.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":"42 2","pages":"137-147"},"PeriodicalIF":1.8,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956043/pdf/nihms-1629074.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38382033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Michael Kay Reedy","authors":"K. Taylor","doi":"10.1007/s10974-021-09602-0","DOIUrl":"https://doi.org/10.1007/s10974-021-09602-0","url":null,"abstract":"","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":"42 1","pages":"131 - 135"},"PeriodicalIF":2.7,"publicationDate":"2021-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10974-021-09602-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41838204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Richard Tregear, Co-founder of the Journal of Muscle Research and Cell Motility","authors":"S. Marston","doi":"10.1007/s10974-021-09600-2","DOIUrl":"https://doi.org/10.1007/s10974-021-09600-2","url":null,"abstract":"","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":"42 1","pages":"129 - 130"},"PeriodicalIF":2.7,"publicationDate":"2021-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10974-021-09600-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43524216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of decay kinetics of the cytosolic calcium transient induced by oxytocin in rat myometrium smooth muscle cells.","authors":"S O Karakhim,&nbsp;S G Shlykov,&nbsp;L G Babich,&nbsp;D V Sinko","doi":"10.1007/s10974-021-09598-7","DOIUrl":"https://doi.org/10.1007/s10974-021-09598-7","url":null,"abstract":"<p><p>The method of kinetic analysis of the relaxation phase of the mechanical response of the smooth muscle previously proposed by Burdyga and Kosterin was applied to study the dynamics of the decay of oxytocin-induced calcium transients in cytosol of the rat myometrium smooth muscle cell detected by a fluorescence signal generated by a calcium-sensitive probe fluo-4 using a laser scanning confocal microscope. The experimental data were well linearized in the coordinates ln [(F_m - F)/F] vs lnt (F and F_m are the current fluorescence intensity of the calcium probe and the fluorescence intensity at the maximum of the calcium transient, respectively, while t is the time). The empirical parameters n and τ were determined by which the maximal normalized relaxation rate V_n was calculated for five different ROIs (regions of interest) in the myocyte cytosol. It proved to be almost the same for all ROIs. The maximal normalized relaxation rate calculated from the fluorescence intensity was always lower than that calculated from the corresponding calcium concentration, i.e. the cytosolic Ca²⁺ concentration in the relaxation phase decreases faster than the corresponding fluorescence intensity. The value of the maximal normalized relaxation rate calculated both from the fluorescence intensity and from the force of oxytocin-induced contractions of isolated rat uterus longitudinal smooth muscles (according to Tsymbalyuk and Kosterin) was exactly the same. This indicates that in the relaxation phase, the decreasing curves of both the fluorescence intensity and the contraction forces coincide.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":"42 1","pages":"117-127"},"PeriodicalIF":2.7,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10974-021-09598-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25372496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of voluntary wheel running on mitochondrial content and dynamics in rat skeletal muscle.","authors":"Barnaby P Frankish,&nbsp;Petra Najdovska,&nbsp;Hongyang Xu,&nbsp;Stefan G Wette,&nbsp;Robyn M Murphy","doi":"10.1007/s10974-020-09580-9","DOIUrl":"https://doi.org/10.1007/s10974-020-09580-9","url":null,"abstract":"<p><p>This study reports that in rat skeletal muscle the proteins specifically responsible for mitochondrial dynamics, mitofusin-2 (MFN2) and mitochondrial dynamics protein 49 (MiD49), are higher (p < 0.05) in oxidative soleus (SOL) muscle compared with predominantly glycolytic extensor digitorum longus (EDL) muscle, but not seen for optic atrophy 1 (OPA1; p = 0.06). Markers of mitochondrial content, complex I component, NADH:Ubiquinone oxidoreductase subunit A9 (NDUFA9) and complex IV protein, cytochrome C oxidase subunit IV (COXIV; p < 0.05) were also higher in SOL compared with EDL muscle; however, there was no difference in mitochondrial content between muscles, as measured using a citrate synthase assay (p > 0.05). SOL and EDL muscles were compared between age-matched sedentary rats that were housed individually with (RUN) or without (SED) free-access to a running wheel for 12 weeks and showed no change in mitochondrial content, as examined by the abundances of NDUFA9 and COXIV proteins, as well as citrate synthase activity, in either muscle (p > 0.05). Compared to SED animals, MiD49 and OPA1 were not different in either EDL or SOL muscles, and MFN2 was higher in SOL muscles from RUN rats (p < 0.05). Overall, these findings reveal that voluntary wheel running is an insufficient stimulus to result in a significantly higher abundance of most markers of mitochondrial content or dynamics, and it is likely that a greater stimulus, such as either adding resistance to the wheel or an increase in running volume by using a treadmill, is required for mitochondrial adaptation in rat skeletal muscle.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":"42 1","pages":"67-76"},"PeriodicalIF":2.7,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10974-020-09580-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37962929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue specific expression of sialic acid metabolic pathway: role in GNE myopathy.","authors":"Kapila Awasthi,&nbsp;Alok Srivastava,&nbsp;Sudha Bhattacharya,&nbsp;Alok Bhattacharya","doi":"10.1007/s10974-020-09590-7","DOIUrl":"https://doi.org/10.1007/s10974-020-09590-7","url":null,"abstract":"<p><p>GNE myopathy is an adult-onset degenerative muscle disease that leads to extreme disability in patients. Biallelic mutations in the rate-limiting enzyme UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine-kinase (GNE) of sialic acid (SA) biosynthetic pathway, was shown to be the cause of this disease. Other genetic disorders with muscle pathology where defects in glycosylation are known. It is yet not clear why a defect in SA biosynthesis and glycosylation affect muscle cells selectively even though they are ubiquitously present in all tissues. Here we have comprehensively examined the complete SA metabolic pathway involving biosynthesis, sialylation, salvage, and catabolism. To understand the reason for tissue-specific phenotype caused by mutations in genes of this pathway, we analysed the expression of different SA pathway genes in various tissues, during the muscle tissue development and in muscle tissues from GNE myopathy patients (p.Met743Thr) using publicly available databases. We have also analysed gene co-expression networks with GNE in different tissues as well as gene interactions that are unique to muscle tissues only. The results do show a few muscle specific interactions involving ANLN, MYO16 and PRAMEF25 that could be involved in specific phenotype. Overall, our results suggest that SA biosynthetic and catabolic genes are expressed at a very low level in skeletal muscles that also display a unique gene interaction network.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":"42 1","pages":"99-116"},"PeriodicalIF":2.7,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10974-020-09590-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38466217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of AMPK in regulation of Na⁺,K⁺-ATPase in skeletal muscle: does the gauge always plug the sink?","authors":"Sergej Pirkmajer,&nbsp;Metka Petrič,&nbsp;Alexander V Chibalin","doi":"10.1007/s10974-020-09594-3","DOIUrl":"https://doi.org/10.1007/s10974-020-09594-3","url":null,"abstract":"<p><p>AMP-activated protein kinase (AMPK) is a cellular energy gauge and a major regulator of cellular energy homeostasis. Once activated, AMPK stimulates nutrient uptake and the ATP-producing catabolic pathways, while it suppresses the ATP-consuming anabolic pathways, thus helping to maintain the cellular energy balance under energy-deprived conditions. As much as ~ 20-25% of the whole-body ATP consumption occurs due to a reaction catalysed by Na⁺,K⁺-ATPase (NKA). Being the single most important sink of energy, NKA might seem to be an essential target of the AMPK-mediated energy saving measures, yet NKA is vital for maintenance of transmembrane Na⁺ and K⁺ gradients, water homeostasis, cellular excitability, and the Na⁺-coupled transport of nutrients and ions. Consistent with the model that AMPK regulates ATP consumption by NKA, activation of AMPK in the lung alveolar cells stimulates endocytosis of NKA, thus suppressing the transepithelial ion transport and the absorption of the alveolar fluid. In skeletal muscles, contractions activate NKA, which opposes a rundown of transmembrane ion gradients, as well as AMPK, which plays an important role in adaptations to exercise. Inhibition of NKA in contracting skeletal muscle accentuates perturbations in ion concentrations and accelerates development of fatigue. However, different models suggest that AMPK does not inhibit or even stimulates NKA in skeletal muscle, which appears to contradict the idea that AMPK maintains the cellular energy balance by always suppressing ATP-consuming processes. In this short review, we examine the role of AMPK in regulation of NKA in skeletal muscle and discuss the apparent paradox of AMPK-stimulated ATP consumption.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":"42 1","pages":"77-97"},"PeriodicalIF":2.7,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10974-020-09594-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38781764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcium sensitivity during staircase with sequential incompletely fused contractions.","authors":"Lisa D Glass,&nbsp;Arthur J Cheng,&nbsp;Brian R MacIntosh","doi":"10.1007/s10974-019-09572-4","DOIUrl":"https://doi.org/10.1007/s10974-019-09572-4","url":null,"abstract":"<p><p>Activity dependent potentiation is thought to result from phosphorylation of the regulatory light chains of myosin, increasing Ca²⁺ sensitivity. Yet, Ca²⁺ sensitivity decreases early in a period of intermittent contractions. The purpose of this study was to investigate the early change in Ca²⁺ sensitivity during intermittent submaximal tetanic contractions. Flexor digitorum brevis muscle fibres were dissected from mice after cervical disarticulation. Fibres were superfused with Tyrode solution at 32 °C. Length was set to yield maximal tetanic force. Indo-1 was microinjected into fibres and allowed to dissipate for 30 min. Fluorescence was measured at 405 and 495 nm wavelength and the ratio was used to estimate [Ca²⁺]. A control force-Ca²⁺ relationship was determined with stimulation over a range of frequencies, yielding constants for slope, max force, and half-maximal [Ca²⁺] (pCa^2 +₅₀). Data were collected for sequential contractions at 40 Hz at 2 s intervals. Active force decreased over the first 1-4 contractions then increased. A force-pCa²⁺ curve was fit to each contraction, using the control values for the Hill slope and max force by adjusting pCa²⁺₅₀ until the curve passed through the target contraction. Data are presented for three contractions for each fibre: first, maximum shift to the right, and last contraction. There was a significant shift to the right for pCa²⁺₅₀ (decreased Ca²⁺ sensitivity), usually early in the series of intermittent contractions, then pCa^2 +₅₀ shifted to the left, but remained significantly different from the control value. Although potentiation is associated with increased Ca²⁺ sensitivity, this increase begins only after Ca²⁺ sensitivity has decreased and, in most cases, Ca²⁺ sensitivity does not increase above the control level.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":"42 1","pages":"59-65"},"PeriodicalIF":2.7,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10974-019-09572-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37523896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiotoxin-induced skeletal muscle injury elicits profound changes in anabolic and stress signaling, and muscle fiber type composition.","authors":"Sebastiaan Dalle,&nbsp;Charlotte Hiroux,&nbsp;Chiel Poffé,&nbsp;Monique Ramaekers,&nbsp;Louise Deldicque,&nbsp;Katrien Koppo","doi":"10.1007/s10974-020-09584-5","DOIUrl":"https://doi.org/10.1007/s10974-020-09584-5","url":null,"abstract":"<p><p>To improve muscle healing upon injury, it is of importance to understand the interplay of key signaling pathways during muscle regeneration. To study this, mice were injected with cardiotoxin (CTX) or PBS in the Tibialis Anterior muscle and were sacrificed 2, 5 and 12 days upon injection. The time points represent different phases of the regeneration process, i.e. destruction, repair and remodeling, respectively. Two days upon CTX-injection, p-mTORC1 signaling and stress markers such as BiP and p-ERK1/2 were upregulated. Phospho-ERK1/2 and p-mTORC1 peaked at d5, while BiP expression decreased towards PBS levels. Phospho-FOXO decreased 2 and 5 days following CTX-injection, indicative of an increase in catabolic signaling. Furthermore, CTX-injection induced a shift in the fiber type composition, characterized by an initial loss in type IIa fibers at d2 and at d5. At d5, new type IIb fibers appeared, whereas type IIa fibers were recovered at d12. To conclude, CTX-injection severely affected key modulators of muscle metabolism and histology. These data provide useful information for the development of strategies that aim to improve muscle molecular signaling and thereby recovery.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":"41 4","pages":"375-387"},"PeriodicalIF":2.7,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10974-020-09584-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38115272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}