scholarly journals Role of the cytoskeleton in muscle transcriptional responses to altered use

2013 ◽  
Vol 45 (8) ◽  
pp. 321-331 ◽  
Author(s):  
Gretchen A. Meyer ◽  
Simon Schenk ◽  
Richard L. Lieber

In this work, the interaction between the loss of a primary component of the skeletal muscle cytoskeleton, desmin, and two common physiological stressors, acute mechanical injury and aging, were investigated at the transcriptional, protein, and whole muscle levels. The transcriptional response of desmin knockout ( des −/−) plantarflexors to a bout of 50 eccentric contractions (ECCs) showed substantial overlap with the response in wild-type ( wt) muscle. However, changes in the expression of genes involved in muscle response to injury were blunted in adult des −/− muscle compared with wt (fold change with ECC in des −/− and wt, respectively: Mybph, 1.4 and 2.9; Xirp1, 2.2 and 5.7; Csrp3, 1.8 and 4.3), similar to the observed blunted mechanical response (torque drop: des −/− 30.3% and wt 55.5%). Interestingly, in the absence of stressors, des −/− muscle exhibited elevated expression of many these genes compared with wt. The largest transcriptional changes were observed in the interaction between aging and the absence of desmin, including many genes related to slow fiber pathway (Myh7, Myl3, Atp2a2, and Casq2) and insulin sensitivity (Tlr4, Trib3, Pdk3, and Pdk4). Consistent with these transcriptional changes, adult des −/− muscle exhibited a significant fiber type shift from fast to slow isoforms of myosin heavy chain ( wt, 5.3% IIa and 71.7% IIb; des −/−, 8.4% IIa and 61.4% IIb) and a decreased insulin-stimulated glucose uptake ( wt, 0.188 μmol/g muscle/20 min; des −/−, 0.085 μmol/g muscle/20 min). This work points to novel areas of influence of this cytoskeletal protein and directs future work to elucidate its function.

2008 ◽  
Vol 35 (1) ◽  
pp. 86-95 ◽  
Author(s):  
Marianna Evans ◽  
Kevin Morine ◽  
Cyelee Kulkarni ◽  
Elisabeth R. Barton

Distinctions between craniofacial and axial muscles exist from the onset of development and throughout adulthood. The masticatory muscles are a specialized group of craniofacial muscles that retain embryonic fiber properties in the adult, suggesting that the developmental origin of these muscles may govern a pattern of expression that differs from limb muscles. To determine the extent of these differences, expression profiling of total RNA isolated from the masseter and tibialis anterior (TA) muscles of adult female mice was performed, which identified transcriptional changes in unanticipated functional classes of genes in addition to those attributable to fiber type. In particular, the masseters displayed a reduction of transcripts associated with contractile and cytoskeletal load-sensing and anabolic processes, and heightened expression of genes associated with stress. Associated with these observations was a significantly smaller fiber cross-sectional area in masseters, significantly elevated load-sensing signaling (phosphorylated focal adhesion kinase), and increased apoptotic index in masseters compared with TA muscles. Based on these results, we hypothesize that masticatory muscles may have a fundamentally different strategy for muscle design, compared with axial muscles. Specifically there are small diameter fibers that have an attenuated ability to hypertrophy, but an increased propensity to undergo apoptosis. These results may provide insight into the molecular basis for specific muscle-related pathologies associated with masticatory muscles.


2021 ◽  
Author(s):  
Jeanette B Moss ◽  
Christopher B Cunningham ◽  
Elizabeth C McKinney ◽  
Allen J. Moore

Parenting buffers offspring from hostile environments, but it is not clear how or if the genes that underlie parenting change their expression under environmental stress. We recently demonstrated that for the subsocial carrion beetle, Nicrophorus orbicollis, temperature during parenting does not affect parenting phenotypes. Here, we ask if transcriptional changes associated with parenting are likewise robust to environmental stress. The absence of a transcriptional response for parenting under stress would suggest that the genetic programs for parenting and being parented are canalized. Conversely, a robust transcriptional response would suggest that plasticity of underlying gene expression is critical for maintaining behavioral stability, and that these mechanisms provide a potential target for selection in the face of environmental change. We test these alternatives by characterizing gene expression of parents and offspring with and without parent-offspring interactions under a benign and a stressful temperature. We found that parent-offspring interactions elicit distinct transcriptional responses of parents and larvae irrespective of temperature. We further detected robust changes of gene expression in beetles breeding at 24 degrees C compared to 20 degrees C irrespective of family interaction. However, no strong interaction between parent-offspring interaction and temperature was detected for either parents or larvae. We therefore conclude that canalization, not plasticity of gene expression, most likely explains the absence of behavioral plasticity under thermal stress. This result suggests that species may not have the genetic variation needed to respond to all environmental change, especially for complex phenotypes.


2015 ◽  
Vol 81 (7) ◽  
pp. 2554-2561 ◽  
Author(s):  
Onur Ercan ◽  
Michiel Wels ◽  
Eddy J. Smid ◽  
Michiel Kleerebezem

ABSTRACTThis paper describes the transcriptional adaptations of nongrowing, retentostat cultures ofLactococcus lactisto starvation. Near-zero-growth cultures (μ = 0.0001 h−1) obtained by extended retentostat cultivation were exposed to starvation by termination of the medium supply for 24 h, followed by a recovery period of another 24 h by reinitiating the medium supply to the retentostat culture. During starvation, the viability of the culture was largely retained, and the expression of genes involved in transcription and translational machineries, cell division, and cell membrane energy metabolism was strongly repressed. Expression of these genes was largely recovered following the reinitiation of the medium supply. Starvation triggered the elevated expression of genes associated with synthesis of branched-chain amino acids, histidine, purine, and riboflavin. The expression of these biosynthesis genes was found to remain at an elevated level after reinitiation of the medium supply. In addition, starvation induced the complete gene set predicted to be involved in natural competence inL. lactisKF147, and the elevated expression of these genes was sustained during the subsequent recovery period, but our attempts to experimentally demonstrate natural transformation in these cells failed. Mining the starvation response gene set identified a conservedcis-acting element that resembles the lactococcal CodY motif in the upstream regions of genes associated with transcription and translational machineries, purine biosynthesis, and natural transformation inL. lactis, suggesting a role for CodY in the observed transcriptome adaptations to starvation in nongrowing cells.


2017 ◽  
Author(s):  
MacManes Matthew

AbstractAnimal living in desert environments are forced to survive despite severe heat, intense solar radiation, and both acute and chronic dehydration. Indeed, these animals have evolved phenotypes that effectively address these environmental stressors. To begin to understand the ways in which the desert adapted rodent P. eremicus survives, we performed an experiment by which we subjected reproductively mature adults to profound acute dehydration, during which they lost on average 23% of their body weight. Animals react via a series of changes in the kidney, which include modulating expression of genes responsible for reducing the rate of transcription, and maintaining water and salt balance. Extracellular matrix turnover appears to be decreased, and apoptosis is limited. Serum Creatinine and other biomarkers of kidney injury are not elevated, which is different than the canonical human response, suggesting that transcriptional changes caused by acute dehydration effectively prohibit widespread kidney damage in the cactus mouse.


2013 ◽  
Vol 45 (15) ◽  
pp. 653-666 ◽  
Author(s):  
Maia J. Benner ◽  
Matt L. Settles ◽  
Gordon K. Murdoch ◽  
Ronald W. Hardy ◽  
Barrie D. Robison

The potential benefits of selenium (Se) supplementation are currently under investigation for prevention of certain cancers and treatment of neurological disorders. However, little is known concerning the response of the brain to increased dietary Se under conditions of Se sufficiency, despite the majority of Se supplementation trials occurring in healthy, Se sufficient subjects. We evaluated the transcriptional response of Se-dependent genes, selenoproteins and the genes necessary for their synthesis (the selenoproteome), in the zebrafish ( Danio rerio) brain to supplementation with nutritionally relevant levels of dietary Se (sodium selenite) during conditions of assumed Se sufficiency. We first used a microarray approach to analyze the response of the brain selenoproteome to dietary Se supplementation for 14 days and then assessed the immediacy and time-scale transcriptional response of the brain selenoproteome to 1, 7, and 14 days of Se supplementation by quantitative real-time PCR (qRT-PCR). The microarray approach did not indicate large-scale influences of Se on the brain transcriptome as a whole or the selenoproteome specifically; only one nonselenoproteome gene (si:ch73-44m9.2) was significantly differentially expressed. Our qRT-PCR results, however, indicate that increases of dietary Se cause small, but significant transcriptional changes within the brain selenoproteome, even after only 1 day of supplementation. These responses were dynamic over a short period of supplementation in a manner highly dependent on sex and the duration of Se supplementation. In nutritional intervention studies, it may be necessary to utilize methods such as qRT-PCR, which allow larger sample sizes, for detecting subtle transcriptional changes in the brain.


2018 ◽  
Author(s):  
Jack C. Schultz ◽  
Patrick P. Edger ◽  
Mélanie J.A. Body ◽  
Heidi M. Appel

AbstractSome insects can redirect plant development to form unique organs called galls, which provide these insects with unique, enhanced food and protection from enemies and the elements. Many galls resemble flowers or fruits, suggesting that elements of reproductive development may be involved. We tested this hypothesis using RNA sequencing (RNAseq) to quantify the transcriptional responses of wild grapevine (Vitis riparia Michx.) leaves to a galling parasite, phylloxera (Daktulosphaira vitifolia (Fitch 1855)). If development of reproductive structures is part of gall formation, we expected to find significantly elevated expression of genes involved in flower and/or fruit development in developing galls as opposed to ungalled leaves. We found that reproductive gene ontology (GO) categories were significantly enriched in developing galls, and that expression of many candidate genes involved in floral development were significantly increased, particularly in later gall stages. The patterns of gene expression found in galls suggest that phylloxera exploits vascular cambium to provide meristematic tissue and redirects leaf development towards formation of carpels. The phylloxera leaf gall appears to be phenotypically and transcriptionally similar to the carpel, due to the parasite hijacking underlying genetic machinery in the host plant.


2005 ◽  
Vol 73 (2) ◽  
pp. 1069-1080 ◽  
Author(s):  
Nicholas H. Bergman ◽  
Karla D. Passalacqua ◽  
Renee Gaspard ◽  
Lynne M. Shetron-Rama ◽  
John Quackenbush ◽  
...  

ABSTRACT Interactions between Bacillus anthracis and host macrophages represent critical early events in anthrax pathogenesis, but their details are not clearly understood. Here we report the first genomewide characterization of the transcriptional changes within macrophages infected with B. anthracis and the identification of several hundred host genes that were differentially expressed during this intracellular stage of infection. These loci included both genes that are known to be regulated differentially in response to many other bacterial pathogens and those that appear to be differentially regulated in response to B. anthracis but not other bacterial species that have been tested. These data provide a transcriptional basis for a variety of physiological changes observed during infection, including the induction of apoptosis caused by the infecting bacteria. The expression patterns underlying B. anthracis-induced apoptosis led us to test further the importance of one very highly induced macrophage gene, that for ornithine decarboxylase. Our data show that this enzyme plays an important and previously unrecognized role in suppressing apoptosis in B. anthracis-infected cells. We have also characterized the transcriptional response to anthrax lethal toxin in activated macrophages and found that, following toxin treatment, many of the host inflammatory response pathways are dampened. These data provide insights into B. anthracis pathogenesis as well as potential leads for the development of new diagnostic and therapeutic options.


Open Biology ◽  
2017 ◽  
Vol 7 (2) ◽  
pp. 160306 ◽  
Author(s):  
Vincent Jonchère ◽  
Nada Alqadri ◽  
John Herbert ◽  
Lauren Dodgson ◽  
David Mason ◽  
...  

Recent work has implicated the actin cytoskeleton in tissue size control and tumourigenesis, but how changes in actin dynamics contribute to hyperplastic growth is still unclear. Overexpression of Pico, the only Drosophila Mig-10/RIAM/Lamellipodin adapter protein family member, has been linked to tissue overgrowth via its effect on the myocardin-related transcription factor (Mrtf), an F-actin sensor capable of activating serum response factor (SRF). Transcriptional changes induced by acute Mrtf/SRF signalling have been largely linked to actin biosynthesis and cytoskeletal regulation. However, by RNA profiling, we find that the common response to chronic mrtf and pico overexpression in wing discs was upregulation of ribosome protein and mitochondrial genes, which are conserved targets for Mrtf/SRF and are known growth drivers. Consistent with their ability to induce a common transcriptional response and activate SRF signalling in vitro , we found that both pico and mrtf stimulate expression of an SRF-responsive reporter gene in wing discs. In a functional genetic screen, we also identified deterin , which encodes Drosophila Survivin, as a putative Mrtf/SRF target that is necessary for pico -mediated tissue overgrowth by suppressing proliferation-associated cell death. Taken together, our findings raise the possibility that distinct targets of Mrtf/SRF may be transcriptionally induced depending on the duration of upstream signalling.


2015 ◽  
Vol 28 (3) ◽  
pp. 343-361 ◽  
Author(s):  
Catherine Martel ◽  
Vladimir Zhurov ◽  
Marie Navarro ◽  
Manuel Martinez ◽  
Marc Cazaux ◽  
...  

The two-spotted spider mite Tetranychus urticae is one of the most significant mite pests in agriculture, feeding on more than 1,100 plant hosts, including model plants Arabidopsis thaliana and tomato, Solanum lycopersicum. Here, we describe timecourse tomato transcriptional responses to spider mite feeding and compare them with Arabidopsis in order to determine conserved and divergent defense responses to this pest. To refine the involvement of jasmonic acid (JA) in mite-induced responses and to improve tomato Gene Ontology annotations, we analyzed transcriptional changes in the tomato JA-signaling mutant defenseless1 (def-1) upon JA treatment and spider mite herbivory. Overlay of differentially expressed genes (DEG) identified in def-1 onto those from the timecourse experiment established that JA controls expression of the majority of genes differentially regulated by herbivory. Comparison of defense responses between tomato and Arabidopsis highlighted 96 orthologous genes (of 2,133 DEG) that were recruited for defense against spider mites in both species. These genes, involved in biosynthesis of JA, phenylpropanoids, flavonoids, and terpenoids, represent the conserved core of induced defenses. The remaining tomato DEG support the establishment of tomato-specific defenses, indicating profound divergence of spider mite–induced responses between tomato and Arabidopsis.


2018 ◽  
Author(s):  
Yufei Xie ◽  
Sofie Tolmeijer ◽  
Jelle Oskam ◽  
Tijs Tonkens ◽  
Annemarie H. Meijer ◽  
...  

AbstractGlucocorticoid drugs are widely used to treat immune-related diseases, but their use is limited by side effects and by resistance, which especially occurs in macrophage-dominated diseases. In order to improve glucocorticoid therapies, more research is required into the mechanisms of glucocorticoid action. In the present study, we have used a zebrafish model for inflammation to study glucocorticoid effects on the innate immune response. In zebrafish larvae, the migration of neutrophils towards a site of injury is inhibited by the synthetic glucocorticoid beclomethasone, while migration of macrophages is glucocorticoid resistant. We show that wounding-induced increases in expression of genes encoding neutrophil-specific chemoattractants (Il8 and Cxcl18b) are attenuated by beclomethasone, but that beclomethasone does not attenuate the induction of the genes encoding Ccl2 and Cxcl11aa, which we show to be required for macrophage recruitment. RNA sequencing on Fluorescence-Activated Cell Sorting (FACS)-sorted macrophages showed that the vast majority of the wounding-induced transcriptional changes in these cells are inhibited by beclomethasone, whereas a small subset is glucocorticoid-insensitive. As a result, beclomethasone decreases the number of macrophages that differentiate towards a pro-inflammatory (M1) phenotype, which we demonstrated using atnfa:eGFP-Freporter line and analysis of macrophage morphology. We conclude that the glucocorticoid resistance of the wounding-induced macrophage migration is due to the insensitivity of the induction of macrophage-specific chemoattractants to glucocorticoid inhibition, which may explain the relative resistance of macrophage-dominated diseases to glucocorticoid therapy. However, the induction of pro-inflammatory genes in macrophages is strongly attenuated, which inhibits their differentiation to an M1 phenotype.Summary statementIn a zebrafish model for inflammation, glucocorticoids do not affect the migration of macrophages, but inhibit differentiation towards an M1 phenotype, by strongly attenuating transcriptional responses in these cells.


Sign in / Sign up

Export Citation Format

Share Document