scholarly journals S100A1: A Regulator of Striated Muscle Sarcoplasmic Reticulum Ca2+Handling, Sarcomeric, and Mitochondrial Function

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Mirko Völkers ◽  
David Rohde ◽  
Chelain Goodman ◽  
Patrick Most
Keyword(s):  
Skeletal Muscle ◽  
Cardiac Tissue ◽  
Striated Muscle ◽  
Expression Patterns ◽  
S100 Protein ◽  
Muscle Performance ◽  
Therapeutic Interventions ◽  
Downstream Signaling ◽  
Wide Range ◽  
Cardiac Gene

Calcium (Ca2+) signaling plays a key role in a wide range of physiological functions including control of cardiac and skeletal muscle performance. To assure a precise coordination of both temporally and spatially transduction of intracellularCa2+oscillations to downstream signaling networks and target operations,Ca2+cycling regulation in muscle tissue is conducted by a plethora of diverse molecules.Ca2+S100A1 is a member of theCa2+-binding S100 protein family and represents the most abundant S100 isoform in cardiac and skeletal muscle. Early studies revealed distinct expression patterns of S100A1 in healthy and diseased cardiac tissue from animal models and humans. Further elaborate investigations uncovered S100A1 protein as a basic requirement for striated muscleCa2+handling integrity. S100A1 is a critical regulator of cardiomyocyteCa2+cycling and contractile performance. S100A1-mediated inotropy unfolds independent and on top ofβAR-stimulated contractility with unchangedβAR downstream signaling. S100A1 has further been detected at different sites within the cardiac sarcomere indicating potential roles in myofilament function. More recently, a study reported a mitochondrial location of S100A1 in cardiomyocytes. Additionally, normalizing the level of S100A1 protein by means of viral cardiac gene transfer in animal heart failure models resulted in a disrupted progression towards cardiac failure and enhanced survival. This brief review is confined to the physiological and pathophysiological relevance of S100A1 in cardiac and skeletal muscleCa2+handling with a particular focus on its potential as a molecular target for future therapeutic interventions.

scholarly journals The Key Lnc (RNA)s in Cardiac and Skeletal Muscle Development, Regeneration, and Disease

2021 ◽  
Vol 8 (8) ◽  
pp. 84
Author(s):  
Amanda Pinheiro ◽  
Francisco J. Naya
Keyword(s):  
Skeletal Muscle ◽  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Muscle Development ◽  
Striated Muscle ◽  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Therapeutic Interventions ◽  
Skeletal Muscle Development ◽  
Non Coding Rnas

Non-coding RNAs (ncRNAs) play a key role in the regulation of transcriptional and epigenetic activity in mammalian cells. Comprehensive analysis of these ncRNAs has revealed sophisticated gene regulatory mechanisms which finely tune the proper gene output required for cellular homeostasis, proliferation, and differentiation. However, this elaborate circuitry has also made it vulnerable to perturbations that often result in disease. Among the many types of ncRNAs, long non-coding RNAs (lncRNAs) appear to have the most diverse mechanisms of action including competitive binding to miRNA targets, direct binding to mRNA, interactions with transcription factors, and facilitation of epigenetic modifications. Moreover, many lncRNAs display tissue-specific expression patterns suggesting an important regulatory role in organogenesis, yet the molecular mechanisms through which these molecules regulate cardiac and skeletal muscle development remains surprisingly limited. Given the structural and metabolic similarities of cardiac and skeletal muscle, it is likely that several lncRNAs expressed in both of these tissues have conserved functions in establishing the striated muscle phenotype. As many aspects of regeneration recapitulate development, understanding the role lncRNAs play in these processes may provide novel insights to improve regenerative therapeutic interventions in cardiac and skeletal muscle diseases. This review highlights key lncRNAs that function as regulators of development, regeneration, and disease in cardiac and skeletal muscle. Finally, we highlight lncRNAs encoded by imprinted genes in striated muscle and the contributions of these loci on the regulation of gene expression.

scholarly journals Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin-1

2014 ◽  
Vol 307 (6) ◽  
pp. E469-E484 ◽  
Author(s):  
Sue C. Bodine ◽  
Leslie M. Baehr
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Striated Muscle ◽  
Expression Patterns ◽  
Ring Finger ◽  
Physiological Role ◽  
Ubiquitin Ligases ◽  
Skeletal Muscle Atrophy ◽  
E3 Ubiquitin Ligases ◽  
Cellular Functions

Muscle RING finger 1 (MuRF1) and muscle atrophy F-box (MAFbx)/atrogin-1 were identified more than 10 years ago as two muscle-specific E3 ubiquitin ligases that are increased transcriptionally in skeletal muscle under atrophy-inducing conditions, making them excellent markers of muscle atrophy. In the past 10 years much has been published about MuRF1 and MAFbx with respect to their mRNA expression patterns under atrophy-inducing conditions, their transcriptional regulation, and their putative substrates. However, much remains to be learned about the physiological role of both genes in the regulation of mass and other cellular functions in striated muscle. Although both MuRF1 and MAFbx are enriched in skeletal, cardiac, and smooth muscle, this review will focus on the current understanding of MuRF1 and MAFbx in skeletal muscle, highlighting the critical questions that remain to be answered.

scholarly journals Long Non-coding Antisense RNA DDIT4-AS1 Regulates Meningitic Escherichia coli-Induced Neuroinflammation by Promoting DDIT4 mRNA Stability

2022 ◽  
Author(s):  
Bo Yang ◽  
Bojie Xu ◽  
Ruicheng Yang ◽  
Jiyang Fu ◽  
Liang Li ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Inflammatory Responses ◽  
Expression Patterns ◽  
Therapeutic Interventions ◽  
E Coli ◽  
Protein Levels ◽  
Wide Range ◽  
The Stability ◽  
Duplex Formation ◽  
The Brain

AbstractOur previous studies have shown that meningitic Escherichia coli can colonize the brain and cause neuroinflammation. Controlling the balance of inflammatory responses in the host central nervous system is particularly vital. Emerging evidence has shown the important regulatory roles of long non-coding RNAs (lncRNAs) in a wide range of biological and pathological processes. However, whether lncRNAs participate in the regulation of meningitic E. coli-mediated neuroinflammation remains unknown. In the present study, we characterized a cytoplasm-enriched antisense lncRNA DDIT4-AS1, which showed similar concordant expression patterns with its parental mRNA DDIT4 upon E. coli infection. DDIT4-AS1 modulated DDIT4 expression at both mRNA and protein levels. Mechanistically, DDIT4-AS1 promoted the stability of DDIT4 mRNA through RNA duplex formation. DDIT4-AS1 knockdown and DDIT4 knockout both attenuated E. coli-induced NF-κB signaling as well as pro-inflammatory cytokines expression, and DDIT4-AS1 regulated the inflammatory response by targeting DDIT4. In summary, our results show that DDIT4-AS1 promotes E. coli-induced neuroinflammatory responses by enhancing the stability of DDIT4 mRNA through RNA duplex formation, providing potential nucleic acid targets for new therapeutic interventions in the treatment of bacterial meningitis.

Mef2 gene expression marks the cardiac and skeletal muscle lineages during mouse embryogenesis

Development ◽  
1994 ◽  
Vol 120 (5) ◽  
pp. 1251-1263 ◽  
Author(s):  
D.G. Edmondson ◽  
G.E. Lyons ◽  
J.F. Martin ◽  
E.N. Olson
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Cardiac Muscle ◽  
Developmental Stages ◽  
Expression Patterns ◽  
Heart Tube ◽  
Mouse Embryogenesis ◽  
Muscle Gene Expression ◽  
Wide Range

Members of the MEF2 family of transcription factors bind a conserved A/T-rich sequence in the control regions of many skeletal and cardiac muscle genes. To begin to assess the roles of the different Mef2 genes in the control of muscle gene expression in vivo, we analyzed by in situ hybridization the expression patterns of the Mef2a, Mef2c and Mef2d genes during mouse embryogenesis. We first detected MEF2C expression at day 7.5 postcoitum (p.c.) in cells of the cardiac mesoderm that give rise to the primitive heart tube, making MEF2C one of the earliest markers for the cardiac muscle lineage yet described. By day 8.5, MEF2A, MEF2C and MEF2D mRNAs are all detected in the myocardium. By day 9.0, MEF2C is expressed in rostral myotomes, where its expression lags by about a day behind that of myf5 and several hours behind that of myogenin. MEF2A and MEF2D are expressed at a lower level than MEF2C in the myotome at day 9.5 and are detected in more embryonic tissues than MEF2C. Expression of each of the MEF2 transcripts is observed in muscle-forming regions within the limbs at day 11.5 p.c. and within muscle fibers throughout the embryo at later developmental stages. The expression of MEF2C in the somites and fetal muscle is distinct from that of MEF2A, MEF2D and the myogenic bHLH regulatory genes, suggesting that it may represent a distinct myogenic cell type. Neural crest cells also express high levels of MEF2 mRNAs between days 8.5 and 10.5 of gestation. After day 12.5 p.c., MEF2 transcripts are detected at high levels in specific regions of the brain and ultimately in a wide range of tissues. The distinct patterns of expression of the different Mef2 genes during mouse embryogenesis suggest that these genes respond to unique developmental cues and support the notion that their products play roles in the regulation of muscle-specific transcription during establishment of the cardiac and skeletal muscle lineages.

Myosin light chain phosphorylation in vertebrate striated muscle: regulation and function

1993 ◽  
Vol 264 (5) ◽  
pp. C1085-C1095 ◽  
Author(s):  
H. L. Sweeney ◽  
B. F. Bowman ◽  
J. T. Stull
Keyword(s):  
Skeletal Muscle ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Striated Muscle ◽  
Low Frequency ◽  
Force Production ◽  
Thick Filament ◽  
Striated Muscles ◽  
Wide Range ◽  
Cross Bridges

The regulatory light chain of myosin (RLC) is phosphorylated in striated muscles by Ca2+/calmodulin-dependent myosin light chain kinase. Unique biochemical and cellular properties of this phosphorylation system in fast-twitch skeletal muscle maintain RLC in the phosphorylated form for a prolonged period after a brief tetanus or during low-frequency repetitive stimulation. This phosphorylation correlates with potentiation of the rate of development and maximal extent of isometric twitch tension. In skinned fibers, RLC phosphorylation increases force production at low levels of Ca2+ activation, via a leftward shift of the force-pCa relationship, and increases the rate of force development over a wide range of activation levels. In heart and slow-twitch skeletal muscle, the functional consequences of RLC phosphorylation are probably similar, and the primary physiological determinants are phosphorylation and dephosphorylation properties unique to each muscle. The mechanism for these physiological responses probably involves movement of the phosphorylated myosin cross bridges away from the thick-filament backbone. The movement of cross bridges may also contribute to the regulation of myosin interactions with actin in vertebrate smooth and invertebrate striated muscles.

Hepatoprotective Role of Berberine on Doxorubicin Induced Hepatotoxicity - Involvement of Cyp

2020 ◽  
Vol 21 (7) ◽  
pp. 541-547
Author(s):  
Bao Sun ◽  
Yue Yang ◽  
Mengzi He ◽  
Yanan Jin ◽  
Xiaoyu Cao ◽  
...  
Keyword(s):  
Drug Metabolism ◽  
Cardiac Tissue ◽  
Liver Toxicity ◽  
Elevated Serum ◽  
Similar Response ◽  
Wide Range ◽  
Cytokine Levels ◽  
Major Organ ◽  
Anti Oxidant

Background: The liver is one of the major organ involved in drug metabolism. Cytochrome P450s are predominantly involved in drug metabolism. A wide range of CYPs have been reported in the liver which have been involved in its normal as well as in diseased conditions. Doxorubicin, one of the most potent chemotherapeutic drugs, although highly efficacious, also has adverse side effects, with its targets being liver and cardiac tissue. Objective: The study aims to evaluate the reversal potentials of berberine on Doxorubicin induced cyp conversion. Methodology: In the present study, the interplay between anti-oxidants, cytochrome and inflammatory markers in DOX induced liver toxicity and its possible reversal by berberine was ascertained. Results: DOX administration significantly elevated serum as well as tissue stress, which was reverted by berberine treatment. A similar response was observed in tissue inflammatory mediators as well as in serum cytokine levels. Most profound reduction in the cytochrome expression was found in Cyp 2B1, 2B2, and 2E1. However, 2C1, 2C6, and 3A1 although showed a decline, but it did not revert the expression back to control levels. Conclusion: It could be concluded that berberine may be an efficient anti-oxidant and immune modulator. It possesses low to moderate cytochrome modulatory potentials.

Cognitive Impact of Cerebellar Damage: Is There a Future for Cognitive Rehabilitation?

2018 ◽  
Vol 17 (3) ◽  
pp. 199-206 ◽  
Author(s):  
Kim van Dun ◽  
Frank V. Overwalle ◽  
Mario Manto ◽  
Peter Marien
Keyword(s):  
Affective Disorders ◽  
Cognitive Rehabilitation ◽  
Therapeutic Interventions ◽  
Posterior Fossa Surgery ◽  
Daily Life Activities ◽  
Wide Range ◽  
Affective Deficits ◽  
Cerebellar Injury ◽  
Cognitive Therapies ◽  
The Impact

Background & Objective: During the past 3 decades, numerous neurophysiological, neuroimaging, experimental and clinical studies have evidenced a crucial role for the cerebellum in cognitive, affective and behavioral functions. As a result of the acknowledged modulatory role of the cerebellum upon remote structures such as the cerebral cortex, cerebellar injury may give rise to a constellation of behavioral, affective and cognitive symptoms (Schmahmann's Syndrome). In sharp contrast to the wide range of therapeutic interventions to treat cognitive and affective disorders following cerebral cortical lesions and despite the consequences of Schmahmann’s syndrome upon daily life activities, the literature is surprisingly only scantly documented with studies investigating the impact of cognitive therapies on cerebellar induced cognitive and affective disorders. This survey aims to present an overview of the therapeutic interventions available in the literature as a possible treatment for Schmahmann’s Syndrome after cerebellar injury, after posterior fossa surgery in children, and in children with neurodevelopmental disorders. Although systematical studies are clearly warranted, available evidence suggests that cerebellar-induced cognitive and affective disorders should be treated in a specific way. Approaches where the patients are explicitly made aware of their deficits and are considered to act as an “external cerebellum” are the most promising. Conclusion: The study of the anatomical connectivity of the cerebellar microcomplexes involved in cognitive/affective deficits is likely to play a major-role in the future.

Linear electrical properties of striated muscle fibres observed with intracellular electrodes

1964 ◽  
Vol 160 (978) ◽  
pp. 69-123 ◽  
Keyword(s):  
Electrical Properties ◽  
Striated Muscle ◽  
Surface Membrane ◽  
Fibre Surface ◽  
Step Function ◽  
Muscle Fibres ◽  
Appreciable Effect ◽  
Current Application ◽  
Current Path ◽  
Wide Range

The linear electrical properties of muscle fibres have been examined using intracellular electrodes for a. c. measurements and analyzing observations on the basis of cable theory. The measurements have covered the frequency range 1 c/s to 10 kc/s. Comparison of the theory for the circular cylindrical fibre with that for the ideal, one-dimensional cable indicates that, under the conditions of the experiments, no serious error would be introduced in the analysis by the geometrical idealization. The impedance locus for frog sartorius and crayfish limb muscle fibres deviates over a wide range of frequencies from that expected for a simple model in which the current path between the inside and the outside of the fibre consists only of a resistance and a capacitance in parallel. A good fit of the experimental results on frog fibres is obtained if the inside-outside admittance is considered to contain, in addition to the parallel elements R m = 3100 Ωcm 2 and C m = 2.6 μF/cm 2 , another path composed of a resistance R e = 330 Ωcm 2 in series with a capacitance C e = 4.1 μF/cm 2 , all referred to unit area of fibre surface. The impedance behaviour of crayfish fibres can be described by a similar model, the corresponding values being R m = 680 Ωcm 2 , C m = 3.9 μF/cm 2 , R e = 35 Ωcm 2 , C e = 17 μF/cm 2 . The response of frog fibres to a step-function current (with the points of voltage recording and current application close together) has been analyzed in terms of the above two-time constant model, and it is shown that neglecting the series resistance would have an appreciable effect on the agreement between theory and experiment only at times less than the halftime of rise of the response. The elements R m and C m are presumed to represent properties of the surface membrane of the fibre. R e and C e are thought to arise not at the surface, but to be indicative of a separate current path from the myoplasm through an intracellular system of channels to the exterior. In the case of crayfish fibres, it is possible that R e (when referred to unit volume) would be a measure of the resistivity of the interior of the channels, and C e the capacitance across the walls of the channels. In the case of frog fibres, it is suggested that the elements R e , C e arise from the properties of adjacent membranes of the triads in the sarcoplasmic reticulum . The possibility is considered that the potential difference across the capacitance C e may control the initiation of contraction.

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