scholarly journals Severe acute dehydration in a desert rodent elicits a transcriptional response that effectively prevents kidney injury

2017 ◽  
Author(s):  
MacManes Matthew
Keyword(s):  
Transcriptional Response ◽  
Kidney Injury ◽  
Environmental Stressors ◽  
Human Response ◽  
Mature Adults ◽  
Expression Of Genes ◽  
Desert Rodent ◽  
Transcriptional Changes ◽  
Intense Solar Radiation ◽  
Water And Salt Balance

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.

scholarly journals Severe acute dehydration in a desert rodent elicits a transcriptional response that effectively prevents kidney injury

2017 ◽  
Vol 313 (2) ◽  
pp. F262-F272 ◽  
Author(s):  
Matthew David MacManes
Keyword(s):  
Transcriptional Response ◽  
Kidney Injury ◽  
Environmental Stressors ◽  
Human Response ◽  
Mature Adults ◽  
Expression Of Genes ◽  
Desert Rodent ◽  
Peromyscus Eremicus ◽  
Intense Solar Radiation ◽  
Water And Salt Balance

Animals living in desert environments are forced to survive despite severe heat, intense solar radiation, and both acute and chronic dehydration. These animals have evolved phenotypes that effectively address these environmental stressors. To begin to understand the ways in which the desert-adapted rodent Peromyscus eremicus survives, reproductively mature adults were subjected to 72 h of water deprivation, during which they lost, on average, 23% of their body weight. The animals reacted via a series of changes in the kidney, which included modulating expression of genes responsible for reducing the rate of transcription and maintaining water and salt balance. Extracellular matrix turnover appeared to be decreased, and apoptosis was limited. In contrast to the canonical human response, serum creatinine and other biomarkers of kidney injury were not elevated, suggesting that changes in gene expression related to acute dehydration may effectively prohibit widespread kidney damage in the cactus mouse.

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
Keyword(s):  
Mechanical Response ◽  
Fiber Type ◽  
Transcriptional Response ◽  
Primary Component ◽  
Transcriptional Responses ◽  
Expression Of Genes ◽  
Elevated Expression ◽  
Transcriptional Changes ◽  
Type Shift ◽  
Future Work

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.

Transcriptome-based identification of pro- and antioxidative gene expression in kidney cortex of nitric oxide-depleted rats

2007 ◽  
Vol 28 (2) ◽  
pp. 158-167 ◽  
Author(s):  
Sebastiaan Wesseling ◽  
Jaap A. Joles ◽  
Harry van Goor ◽  
Hans A. Bluyssen ◽  
Patrick Kemmeren ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Transcriptional Response ◽  
Kidney Injury ◽  
Kidney Cortex ◽  
Heme Oxygenase 1 ◽  
Sprague Dawley ◽  
Expression Of Genes ◽  
Proinflammatory Gene ◽  
Kidney Injury Molecule 1

Nitric oxide (NO) depletion in rats induces severe endothelial dysfunction within 4 days. Subsequently, hypertension and renal injury develop, which are ameliorated by α-tocopherol (VitE) cotreatment. The hypothesis of the present study was that NO synthase (NOS) inhibition induces a renal cortical antioxidative transcriptional response and invokes pro-oxidative and proinflammatory gene expression due to elimination of dampening effects of NO and enhanced oxidative stress. Male Sprague-Dawley rats received NOS inhibitor Nω-nitro-l-arginine (l-NNA, 500 mg/l water) for 4 (4d-LNNA), 21 (21d-LNNA), or 21 days with VitE in chow (0.7 g/kg body wt/day). Renal cortical RNA was applied to oligonucleotide rat arrays. In 4d-LNNA, 21d-LNNA, and 21d-LNNA+VitE, 120, 320, and 184 genes were differentially expressed, respectively. Genes related to glutathione and bilirubin synthesis were suppressed during 4d and 21d-LNNA and not corrected by VitE. Proteinuria, tubulointerstitial macrophages, and heme-oxygenase-1 (HO-1) expression were strongly correlated. Remarkably, pro-oxidative genes were not induced. Inflammation- and injury-related genes, including kidney injury molecule-1 and osteopontin, were unchanged at day 4, induced at 21d, and partly corrected by VitE. Superimposing HO-1 inhibition on NOS inhibition had no impact on the development of hypertension. To summarize, renal expression of genes involved in synthesis of the antioxidants glutathione and bilirubin seemed directly NO dependent, but there were no direct effects of NO depletion on pro-oxidant systems. This indicates that renal transcriptional regulation of two defense systems, glutathione and bilirubin syntheses, seems to depend upon adequate NO synthesis. Interaction between NO synthesis and heme degradation pathways for blood pressure regulation was not found.

scholarly journals Multi-omics analysis reveals contextual tumor suppressive and oncogenic gene modules within the acute hypoxic response

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zdenek Andrysik ◽  
Heather Bender ◽  
Matthew D. Galbraith ◽  
Joaquin M. Espinosa
Keyword(s):  
Cancer Biology ◽  
Acute Hypoxia ◽  
Transcriptional Response ◽  
Adaptation To Hypoxia ◽  
Mtor Inhibition ◽  
Collagen Remodeling ◽  
Acute Response ◽  
Relative Contribution ◽  
Transcriptional Changes ◽  
Cancer Types

AbstractCellular adaptation to hypoxia is a hallmark of cancer, but the relative contribution of hypoxia-inducible factors (HIFs) versus other oxygen sensors to tumorigenesis is unclear. We employ a multi-omics pipeline including measurements of nascent RNA to characterize transcriptional changes upon acute hypoxia. We identify an immediate early transcriptional response that is strongly dependent on HIF1A and the kinase activity of its cofactor CDK8, includes indirect repression of MYC targets, and is highly conserved across cancer types. HIF1A drives this acute response via conserved high-occupancy enhancers. Genetic screen data indicates that, in normoxia, HIF1A displays strong cell-autonomous tumor suppressive effects through a gene module mediating mTOR inhibition. Conversely, in advanced malignancies, expression of a module of HIF1A targets involved in collagen remodeling is associated with poor prognosis across diverse cancer types. In this work, we provide a valuable resource for investigating context-dependent roles of HIF1A and its targets in cancer biology.

scholarly journals In VivoStudies Suggest that Induction of VanS-Dependent Vancomycin Resistance Requires Binding of the Drug to d-Ala-d-Ala Termini in the Peptidoglycan Cell Wall

2013 ◽  
Vol 57 (9) ◽  
pp. 4470-4480 ◽  
Author(s):  
Min Jung Kwun ◽  
Gabriela Novotna ◽  
Andrew R. Hesketh ◽  
Lionel Hill ◽  
Hee-Jeon Hong
Keyword(s):  
Cell Wall ◽  
Transcriptional Activation ◽  
Streptomyces Coelicolor ◽  
Constitutive Expression ◽  
Transcriptional Response ◽  
Vancomycin Resistance ◽  
Content Type ◽  
Expression Of Genes ◽  
Peptidoglycan Cell Wall

ABSTRACTVanRS two-component regulatory systems are key elements required for the transcriptional activation of inducible vancomycin resistance genes in bacteria, but the precise nature of the ligand signal that activates these systems has remained undefined. Using the resistance system inStreptomyces coelicoloras a model, we have undertaken a series ofin vivostudies which indicate that the VanS sensor kinase in VanB-type resistance systems is activated by vancomycin in complex with thed-alanyl-d-alanine (d-Ala-d-Ala) termini of cell wall peptidoglycan (PG) precursors. Complementation of an essentiald-Ala-d-Ala ligase activity by constitutive expression ofvanAencoding a bifunctionald-Ala-d-Ala andd-alanyl-d-lactate (d-Ala-d-Lac) ligase activity allowed construction of strains that synthesized variable amounts of PG precursors containingd-Ala-d-Ala. Assays quantifying the expression of genes under VanRS control showed that the response to vancomycin in these strains correlated with the abundance ofd-Ala-d-Ala-containing PG precursors; strains producing a lower proportion of PG precursors terminating ind-Ala-d-Ala consistently exhibited a lower response to vancomycin. Pretreatment of wild-type cells with vancomycin or teicoplanin to saturate and mask thed-Ala-d-Ala binding sites in nascent PG also blocked the transcriptional response to subsequent vancomycin exposure, and desleucyl vancomycin, a vancomycin analogue incapable of interacting withd-Ala-d-Ala residues, failed to inducevangene expression. Activation of resistance by a vancomycin–d-Ala-d-Ala PG complex predicts a limit to the proportion of PG that can be derived from precursors terminating ind-Ala-d-Lac, a restriction also enforced by the bifunctional activity of the VanA ligase.

scholarly journals Coordinated multitissue transcriptional and plasma metabonomic profiles following acute caloric restriction in mice

2006 ◽  
Vol 27 (3) ◽  
pp. 187-200 ◽  
Author(s):  
Colin Selman ◽  
Nicola D. Kerrison ◽  
Anisha Cooray ◽  
Matthew D. W. Piper ◽  
Steven J. Lingard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Caloric Restriction ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Proton Nuclear Magnetic Resonance ◽  
Cellular Transport ◽  
Expression Of Genes ◽  
Transcriptional Changes

Caloric restriction (CR) increases healthy life span in a range of organisms. The underlying mechanisms are not understood but appear to include changes in gene expression, protein function, and metabolism. Recent studies demonstrate that acute CR alters mortality rates within days in flies. Multitissue transcriptional changes and concomitant metabolic responses to acute CR have not been described. We generated whole genome RNA transcript profiles in liver, skeletal muscle, colon, and hypothalamus and simultaneously measured plasma metabolites using proton nuclear magnetic resonance in mice subjected to acute CR. Liver and muscle showed increased gene expressions associated with fatty acid metabolism and a reduction in those involved in hepatic lipid biosynthesis. Glucogenic amino acids increased in plasma, and gene expression for hepatic gluconeogenesis was enhanced. Increased expression of genes for hormone-mediated signaling and decreased expression of genes involved in protein binding and development occurred in hypothalamus. Cell proliferation genes were decreased and cellular transport genes increased in colon. Acute CR captured many, but not all, hepatic transcriptional changes of long-term CR. Our findings demonstrate a clear transcriptional response across multiple tissues during acute CR, with congruent plasma metabolite changes. Liver and muscle switched gene expression away from energetically expensive biosynthetic processes toward energy conservation and utilization processes, including fatty acid metabolism and gluconeogenesis. Both muscle and colon switched gene expression away from cellular proliferation. Mice undergoing acute CR rapidly adopt many transcriptional and metabolic changes of long-term CR, suggesting that the beneficial effects of CR may require only a short-term reduction in caloric intake.

scholarly journals Transcriptional Changes in Potato Sprouts upon Interaction with Rhizoctonia solani Indicate Pathogen-Induced Interference in the Defence Pathways of Potato

2021 ◽  
Vol 22 (6) ◽  
pp. 3094
Author(s):  
Rita Zrenner ◽  
Bart Verwaaijen ◽  
Franziska Genzel ◽  
Burkhardt Flemer ◽  
Rita Grosch
Keyword(s):  
Rhizoctonia Solani ◽  
Rna Sequencing ◽  
Control Strategies ◽  
Transcriptional Response ◽  
Black Scurf ◽  
Post Inoculation ◽  
Molecular Response ◽  
Resistance Level ◽  
Sequencing Experiment ◽  
Transcriptional Changes

Rhizoctonia solani is the causer of black scurf disease on potatoes and is responsible for high economical losses in global agriculture. In order to increase the limited knowledge of the plants’ molecular response to this pathogen, we inoculated potatoes with R. solani AG3-PT isolate Ben3 and carried out RNA sequencing with total RNA extracted from potato sprouts at three and eight days post inoculation (dpi). In this dual RNA-sequencing experiment, the necrotrophic lifestyle of R. solani AG3-PT during early phases of interaction with its host has already been characterised. Here the potato plants’ comprehensive transcriptional response to inoculation with R. solani AG3 was evaluated for the first time based on significantly different expressed plant genes extracted with DESeq analysis. Overall, 1640 genes were differentially expressed, comparing control (−Rs) and with R. solani AG3-PT isolate Ben3 inoculated plants (+Rs). Genes involved in the production of anti-fungal proteins and secondary metabolites with antifungal properties were significantly up regulated upon inoculation with R. solani. Gene ontology (GO) terms involved in the regulation of hormone levels (i.e., ethylene (ET) and jasmonic acid (JA) at 3 dpi and salicylic acid (SA) and JA response pathways at 8 dpi) were significantly enriched. Contrastingly, the GO term “response to abiotic stimulus” was down regulated at both time points analysed. These results may support future breeding efforts toward the development of cultivars with higher resistance level to black scurf disease or the development of new control strategies.

scholarly journals Dendritic cells’ characteristics in patients with treated systemic lupus erythematosus

2020 ◽  
Author(s):  
Anna Wardowska ◽  
Żaneta Smoleńska ◽  
Katarzyna A. Lisowska ◽  
Zbigniew Zdrojewski ◽  
Michał Pikuła
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Dendritic Cells ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Complement Components ◽  
Expression Of Genes ◽  
Luminex Technology ◽  
Transcriptional Changes ◽  
Chronic Autoimmune Disease

The systemic lupus erythematosus (SLE) is a chronic autoimmune disease related to a loss of immune tolerance against autoantigens that leads to tissue inflammation and organ dysfunction. Constant stimulation of dendritic cells (DC) with autoantigens is hypothesized to increase the B cells’ activity which are involved in production of autoantibodies that play an essential role in the SLE development. We focused our study on detecting alterations in DCs at the cellular and molecular levels in patients with treated SLE, depending on the disease activity and treatment. In order to phenotype subpopulations of DCs, multicolor flow cytometry was used. Transcriptional changes were identified with quantitative PCR, while soluble cytokine receptors were assessed with the Luminex technology. We show that SLE patients display a higher percentage of activated myeloid DCs (mDCs) when compared to healthy people. Both, the mDCs and plasmacytoid DCs (pDCs) of SLE patients were characterized by changes in expression of genes associated with their maturation, functioning and signalling, which was especially reflected by low expression of regulatory factor ID2 and increased expression of IRF5. pDCs of SLE patients also showed increased expression of IRF1. There were also significant changes in the expression of APRIL, MBD2, and E2-2 in mDCs that significantly correlated with some serum components, i.e. anti-dsDNA antibodies or complement components. However, we did not find any significant differences depending on the disease activity. While the majority of available studies focuses mainly on the role of pDCs in the disease development, our results show significant disturbances in the functioning of mDCs in SLE patients, thus confirming mDCs’ importance in SLE pathogenesis.

scholarly journals Iodinated contrast media cause direct tubular cell damage, leading to oxidative stress, low nitric oxide, and impairment of tubuloglomerular feedback

2014 ◽  
Vol 306 (8) ◽  
pp. F864-F872 ◽  
Author(s):  
Zhi Zhao Liu ◽  
Kristin Schmerbach ◽  
Yuan Lu ◽  
Andrea Perlewitz ◽  
Tatiana Nikitina ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Trypan Blue ◽  
Cell Damage ◽  
Kidney Injury ◽  
Tubuloglomerular Feedback ◽  
Iodinated Contrast Media ◽  
Expression Of Genes ◽  
Iodinated Contrast ◽  
Direct Cell

Iodinated contrast media (CM) have adverse effects that may result in contrast-induced acute kidney injury. Oxidative stress is believed to play a role in CM-induced kidney injury. We test the hypothesis that oxidative stress and reduced nitric oxide in tubules are consequences of CM-induced direct cell damage and that increased local oxidative stress may increase tubuloglomerular feedback. Rat thick ascending limbs (TAL) were isolated and perfused. Superoxide and nitric oxide were quantified using fluorescence techniques. Cell death rate was estimated using propidium iodide and trypan blue. The function of macula densa and tubuloglomerular feedback responsiveness were measured in isolated, perfused juxtaglomerular apparatuses (JGA) of rabbits. The expression of genes related to oxidative stress and the activity of superoxide dismutase (SOD) were investigated in the renal medulla of rats that received CM. CM increased superoxide concentration and reduced nitric oxide bioavailability in TAL. Propidium iodide fluorescence and trypan blue uptake increased more in CM-perfused TAL than in controls, indicating increased rate of cell death. There were no marked acute changes in the expression of genes related to oxidative stress in medullary segments of Henle's loop. SOD activity did not differ between CM and control groups. The tubuloglomerular feedback in isolated JGA was increased by CM. Tubular cell damage and accompanying oxidative stress in our model are consequences of CM-induced direct cell damage, which also modifies the tubulovascular interaction at the macula densa, and may therefore contribute to disturbances of renal perfusion and filtration.

Aldosterone-stimulated PKC signalling cascades: from receptor to effector

2007 ◽  
Vol 35 (5) ◽  
pp. 1049-1051 ◽  
Author(s):  
W. Thomas ◽  
V. McEneaney ◽  
B.J. Harvey
Keyword(s):  
Protein Kinase ◽  
Growth Factor Receptor ◽  
Transcriptional Response ◽  
Protein Kinase D ◽  
Cell Trafficking ◽  
Signalling Cascades ◽  
Transcriptional Changes ◽  
Epidermal Growth ◽  
Protein Kinase Signalling ◽  
Regulation Of Blood Pressure

Aldosterone plays an important role in the regulation of blood pressure. The effects of this hormone have classically been described in terms of the transcriptional regulation of genes that facilitate electrolyte transport, particularly across high-resistance epithelia. The protein kinase signalling cascades that are rapidly activated in response to aldosterone are emerging as important modulators of the transcriptional response, and may serve to prime cells for the subsequent transcriptional changes. The activation of protein kinase D through an epidermal growth factor receptor transactivation pathway by aldosterone in renal cells has the potential to impact on cell trafficking events that regulate transporter activity.

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