scholarly journals How Can a Histidine Kinase Respond to Mechanical Stress?

2021 ◽  
Vol 12 ◽  
Author(s):  
Linda J. Kenney

Bacteria respond to physical forces perceived as mechanical stress as part of their comprehensive environmental sensing strategy. Histidine kinases can then funnel diverse environmental stimuli into changes in gene expression through a series of phosphorelay reactions. Because histidine kinases are most often embedded in the inner membrane, they can be sensitive to changes in membrane tension that occurs, for example, in response to osmotic stress, or when deformation of the cell body occurs upon encountering a surface before forming biofilms, or inside the host in response to shear stress in the kidney, intestine, lungs, or blood stream. A summary of our recent work that links the histidine kinase EnvZ to mechanical changes in the inner membrane is provided and placed in a context of other bacterial systems that respond to mechanical stress.

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Peng Yu ◽  
Baoli Zhang ◽  
Ming Liu ◽  
Ying Yu ◽  
Ji Zhao ◽  
...  

Background. Mechanical stress-induced cardiac remodeling that results in heart failure is characterized by transcriptional reprogramming of gene expression. However, a systematic study of genomic changes involved in this process has not been performed to date. To investigate the genomic changes and underlying mechanism of cardiac remodeling, we collected and analyzed DNA microarray data for murine transverse aortic constriction (TAC) and human aortic stenosis (AS) from the Gene Expression Omnibus database and the European Bioinformatics Institute. Methods and Results. The differential expression genes (DEGs) across the datasets were merged. The Venn diagrams showed that the number of intersections for early and late cardiac remodeling was 74 and 16, respectively. Gene ontology and protein–protein interaction network analysis showed that metabolic changes, cell differentiation and growth, cell cycling, and collagen fibril organization accounted for a great portion of the DEGs in the TAC model, while in AS patients’ immune system signaling and cytokine signaling displayed the most significant changes. The intersections between the TAC model and AS patients were few. Nevertheless, the DEGs of the two species shared some common regulatory transcription factors (TFs), including SP1, CEBPB, PPARG, and NFKB1, when the heart was challenged by applied mechanical stress. Conclusions. This study unravels the complex transcriptome profiles of the heart tissues and highlighting the candidate genes involved in cardiac remodeling induced by mechanical stress may usher in a new era of precision diagnostics and treatment in patients with cardiac remodeling.


2015 ◽  
Vol 137 (2) ◽  
Author(s):  
Julia C. Chen ◽  
Mardonn Chua ◽  
Raymond B. Bellon ◽  
Christopher R. Jacobs

Osteogenic lineage commitment is often evaluated by analyzing gene expression. However, many genes are transiently expressed during differentiation. The availability of genes for expression is influenced by epigenetic state, which affects the heterochromatin structure. DNA methylation, a form of epigenetic regulation, is stable and heritable. Therefore, analyzing methylation status may be less temporally dependent and more informative for evaluating lineage commitment. Here we analyzed the effect of mechanical stimulation on osteogenic differentiation by applying fluid shear stress for 24 hr to osteocytes and then applying the osteocyte-conditioned medium (CM) to progenitor cells. We analyzed gene expression and changes in DNA methylation after 24 hr of exposure to the CM using quantitative real-time polymerase chain reaction and bisulfite sequencing. With fluid shear stress stimulation, methylation decreased for both adipogenic and osteogenic markers, which typically increases availability of genes for expression. After only 24 hr of exposure to CM, we also observed increases in expression of later osteogenic markers that are typically observed to increase after seven days or more with biochemical induction. However, we observed a decrease or no change in early osteogenic markers and decreases in adipogenic gene expression. Treatment of a demethylating agent produced an increase in all genes. The results indicate that fluid shear stress stimulation rapidly promotes the availability of genes for expression, but also specifically increases gene expression of later osteogenic markers.


2021 ◽  
Vol 22 (9) ◽  
pp. 4678
Author(s):  
Sepideh Parvanian ◽  
Hualian Zha ◽  
Dandan Su ◽  
Lifang Xi ◽  
Yaming Jiu ◽  
...  

Mechanical stress following injury regulates the quality and speed of wound healing. Improper mechanotransduction can lead to impaired wound healing and scar formation. Vimentin intermediate filaments control fibroblasts’ response to mechanical stress and lack of vimentin makes cells significantly vulnerable to environmental stress. We previously reported the involvement of exosomal vimentin in mediating wound healing. Here we performed in vitro and in vivo experiments to explore the effect of wide-type and vimentin knockout exosomes in accelerating wound healing under osmotic stress condition. Our results showed that osmotic stress increases the size and enhances the release of exosomes. Furthermore, our findings revealed that exosomal vimentin enhances wound healing by protecting fibroblasts against osmotic stress and inhibiting stress-induced apoptosis. These data suggest that exosomes could be considered either as a stress modifier to restore the osmotic balance or as a conveyer of stress to induce osmotic stress-driven conditions.


2013 ◽  
Vol 103 (4) ◽  
pp. 322-332 ◽  
Author(s):  
Jérôme Patry ◽  
Richard Belley ◽  
Mario Côté ◽  
Marie-Ludivine Chateau-Degat

Background: Clinical recommendations for the prevention and healing of diabetic foot ulcers (DFUs) are somewhat clear. However, assessment and quantification of the mechanical stress responsible for DFU remain complex. Different pressure variables have been described in the literature to better understand plantar tissue stress exposure. This article reviews the role of pressure and shear forces in the pathogenesis of plantar DFU. Methods: We performed systematic searches of the PubMed and Embase databases, completed by a manual search of the selected studies. From 535 potentially relevant references, 70 studies were included in the full-text review. Results: Variables of plantar mechanical stress relate to vertical pressure, shear stress, and temporality of loading. At this time, in-shoe peak plantar pressure (PPP) is the only reliable variable that can be used to prevent DFU. Although it is a poor predictor of in-shoe PPP, barefoot PPP seems complementary and may be more suitable when evaluating patients with diabetes mellitus and peripheral neuropathy who seem noncompliant with footwear. An in-shoe PPP threshold value of 200 kPa has been suggested to prevent DFU. Other variables, such as peak pressure gradient and peak maximal subsurface shear stress and its depth, seem to be of additional utility. Conclusions: To better assess the at-risk foot and to prevent ulceration, the practitioner should integrate quantitative models of dynamic foot plantar pressures, such as in-shoe and barefoot PPPs, with the regular clinical screening examination. Prospective studies are needed to evaluate causality between other variables of mechanical stress and DFUs. (J Am Podiatr Med Assoc 103(4): 322–332, 2013)


2006 ◽  
Vol 291 (1) ◽  
pp. G26-G34 ◽  
Author(s):  
Hideki Nakatsuka ◽  
Takaaki Sokabe ◽  
Kimiko Yamamoto ◽  
Yoshinobu Sato ◽  
Katsuyoshi Hatakeyama ◽  
...  

Partial hepatectomy causes hemodynamic changes that increase portal blood flow in the remaining lobe, where the expression of immediate-early genes, including plasminogen activator inhibitor-1 (PAI-1), is induced. We hypothesized that a hyperdynamic circulatory state occurring in the remaining lobe induces immediate-early gene expression. In this study, we investigated whether the mechanical force generated by flowing blood, shear stress, induces PAI-1 expression in hepatocytes. When cultured rat hepatocytes were exposed to flow, PAI-1 mRNA levels began to increase within 3 h, peaked at levels significantly higher than the static control levels, and then gradually decreased. The flow-induced PAI-1 expression was shear stress dependent rather than shear rate dependent and accompanied by increased hepatocyte production of PAI-1 protein. Shear stress increased PAI-1 transcription but did not affect PAI-1 mRNA stability. Functional analysis of the 2.1-kb PAI-1 5′-promoter indicated that a 278-bp segment containing transcription factor Sp1 and Ets-1 consensus sequences was critical to the shear stress-dependent increase of PAI-1 transcription. Mutations of both the Sp1 and Ets-1 consensus sequences, but not of either one alone, markedly prevented basal PAI-1 transcription and abolished the response of the PAI-1 promoter to shear stress. EMSA and chromatin immunoprecipitation assays showed binding of Sp1 and Ets-1 to each consensus sequence under static conditions, which increased in response to shear stress. In conclusion, hepatocyte PAI-1 expression is flow sensitive and transcriptionally regulated by shear stress via cooperative interactions between Sp1 and Ets-1.


2020 ◽  
Author(s):  
Inês B. Gomes ◽  
Lúcia Simões ◽  
Manuel Simões

<p>The selection of materials for plumbing application has potential implications on the chemical and microbiological quality of the delivered water. This work aims to evaluate the action of materials with different copper content (0, 57, 96 and 100%) on biofilm formation and control by chlorination and mechanical stress. A strain of <em>Stenotrophomonas maltophilia</em> isolated from drinking water was used as model microorganism and biofilms were developed in a rotating cylinder reactor (RCR) using realism-based shear stress conditions. Biofilms were characterized phenotypically and exposed to three control strategies: 10 mg/l of free chlorine for 10 min; an increased shear stress (equivalent to 1.5 m/s of fluid velocity); and the combination of both treatments. Biofilms formed on the copper materials had lower wet mass and produced significantly lower amounts of extracellular proteins than those formed on stainless steel (0% of copper content). Although, the effects of copper materials on biofilm cell density was not significant, these materials had important impact on the efficacy of chemical and/or mechanical treatments. Biofilms formed on 96 or 100% copper materials had lower content of culturable bacteria than that observed on stainless steel after exposure to chlorine or shear stress. The mechanical treatment used had no relevant effects in biofilm control. The combination of chemical and mechanical treatments only caused higher culturability reduction than chlorine in biofilms formed on 57% copper alloy. The number of viable cells present in bulk water after biofilm treatment with chlorine was lower when biofilms were formed on any of the copper surface. The overall results are of potential importance on the selection of materials for drinking water distribution systems, particularly for house and hospital plumbing systems to overcome the effects from chlorine decay. Copper alloys may have a positive public health impact by reducing the number of viable cells in the delivered water after chlorine exposure and improving the disinfection of DW systems. Moreover, the results demonstrate that residual chlorine and mechanical stress, two strategies conventionally used for disinfection of drinking water distribution systems, failed in <em>S. maltophilia</em> biofilm control.</p> <p><strong>Acknowledgements:</strong></p> <p>This work was the result of the projects: UIDB/00511/2020 of the Laboratory for Process Engineering, Environment, Biotechnology and Energy – LEPABE - funded by national funds through the FCT/MCTES (PIDDAC); PTDC/BII-BTI/30219/2017 - POCI-01-0145-FEDER-030219; POCI-01-0145-FEDER-006939, funded by FEDER funds through COMPETE2020 – Programa Operacional Competitividade e Internacionalização (POCI) and by national funds (PIDDAC) through FCT/MCTES; NORTE-01-0145-FEDER-000005 – LEPABE-2-ECO-INNOVATION, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF).</p>


1988 ◽  
Vol 8 (6) ◽  
pp. 2267-2274 ◽  
Author(s):  
E J Carrazana ◽  
K B Pasieka ◽  
J A Majzoub

We developed a method, termed an H-blot, by which the poly(A) tract of any specific mRNA may be detected by RNA filter hybridization after its removal from the body of the mRNA by a RNase H-catalyzed endonucleolytic cleavage in the 3' untranslated region. Using this method, we studied the modulation of the length of the poly(A) tract of rat vasopressin mRNA in vivo during changes in the levels of this mRNA resulting from a physiologic stimulus, osmotic stress. The poly(A) tract of hypothalamic vasopressin mRNA in hydrated rats was, quite remarkably, approximately 250 nucleotides in length, in contrast to that of somatostatin mRNA, which was approximately 30 nucleotides long. Vasopressin mRNA poly(A) tail length increased progressively from approximately 250 to approximately 400 nucleotides with the application of the hyperosmotic stimulus and declined to base line after its removal; somatostatin mRNA poly(A) tail length did not change during osmotic stress. The poly(A) tract length of total hypothalamic mRNA was between 35 and 140 nucleotides and also did not change with osmotic stress. Modulation of poly(A) tract length of specific mRNAs during stimulation of gene expression may provide an additional level of genetic regulation.


2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Ellen Vercalsteren ◽  
Christine Vranckx ◽  
Liesbeth Frederix ◽  
Max Gooijen ◽  
Ilse Scroyen

AbstractWhen obesity arises, adipose tissue (AT) expands and shifts to an influx of pro-inflammatory cells, leading to a state of chronic AT-inflammation.Furthermore, a western diet (WD) modulates the gut microbiome, increasing intestinal permeability. This facilitates the translocation of endotoxins and even entire bacteria into the blood stream, further contributing to the pro-inflammatory state. Even though it is evident a WD, high in fat and carbohydrates (CHO), can cause AT-inflammation, it is still unclear if fat or CHO is the main inducer. Therefore, we are currently investigating the effect of different CHO-types on AT-inflammation.During 15 weeks, male C57BL/6JRj mice were kept on several diets, consisting of high-fructose (HFRD), high-sucrose-high-fructose (HCFD), high-starch (HSTD) or a WD (n = 10 per group). Weekly monitoring of body weight and food intake was followed by analyses of visceral AT-inflammation. Kruskal-wallis tests were used for statistical analysis.Mice on HSTD and HCD had gained significantly less body weight compared to mice on WD after 15 weeks of diet. Mice on HSTD also gained significantly less body weight compared to mice on HFRD and HCFD. Moreover, mice on HSTD and HCD also had significantly smaller AT-depots as compared to mice on WD. Total plasma cholesterol as well as HDL and LDL levels were significantly lower in mice on HSTD and on HCD as compared to mice on WD. Gene expression analysis revealed a significantly lower expression of several pro-inflammatory markers (F4/80, Arg1, Mannose receptor, TNF, MCP1 and Saa3) in AT of mice on HSTD and on HCD compared to a WD. A HSTD also induced lower AT-expression of MCP1 and Saa3 than a HCFD and Saa3 expression was also significantly lower in the HSTD-group compared to the HFRD-group. Furthermore, Foxp3 expression, a marker for anti-inflammatory Treg cells, was significantly increased in AT of all CHO-diet fed mice as compared to the WD-group.In conclusion, these data suggest that certain dietary carbohydrates, in contrast to a WD, do not induce obesity or AT-inflammation, including lower gene expression of Saa3. It is stated that a WD induces Saa3 expression not only in AT, but also in the colon. Furthermore, since Saa3 is able to bind bacteria and is associated with inflammation, further research is necessary to investigate Saa3 as a possible link between disturbances in the gut microbiota and AT-inflammation.


Plants ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 304 ◽  
Author(s):  
Alexander Hofmann ◽  
Sophia Müller ◽  
Thomas Drechsler ◽  
Mareike Berleth ◽  
Katharina Caesar ◽  
...  

Plants employ a number of phosphorylation cascades in response to a wide range of environmental stimuli. Previous studies in Arabidopsis and yeast indicate that histidine kinase AHK1 is a positive regulator of drought and osmotic stress responses. Based on these studies AHK1 was proposed a plant osmosensor, although the molecular basis of plant osmosensing still remains unknown. To understand the molecular role and signaling mechanism of AHK1 in osmotic stress, we have expressed and purified full-length AHK1 from Arabidopsis in a bacterial host to allow for studies on the isolated transmembrane receptor. Purification of the recombinant protein solubilized from the host membranes was achieved in a single step by metal-affinity chromatography. Analysis of the purified AHK1 by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting show a single band indicating that the preparation is highly pure and devoid of contaminants or degradation products. In addition, gel filtration experiments indicate that the preparation is homogenous and monodisperse. Finally, CD-spectroscopy, phosphorylation activity, dimerization studies, and protein–protein interaction with plant phosphorylation targeting AHP2 demonstrate that the purified protein is functionally folded and acts as phospho-His or phospho-Asp phosphatase. Hence, the expression and purification of recombinant AHK1 reported here provide a basis for further detailed functional and structural studies of the receptor, which might help to understand plant osmosensing and osmosignaling on the molecular level.


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