scholarly journals Applications of the SR4G Transgenic Zebrafish Line for Biomonitoring of Stress-Disrupting Compounds: A Proof-of-Concept Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Amin Nozari ◽  
Selena Do ◽  
Vance L. Trudeau

Transgenic zebrafish models have been successfully used in biomonitoring and risk assessment studies of environmental pollutants, including xenoestrogens, pesticides, and heavy metals. We employed zebrafish larva (transgenic SR4G line) with a cortisol-inducible green fluorescence protein reporter (eGFP) as a model to detect stress responses upon exposure to compounds with environmental impact, including bisphenol A (BPA), vinclozolin (VIN), and fluoxetine (FLX). Cortisol, fluorescence signal, and mRNA levels of eGFP and 11 targeted genes were measured in a homogenized pool of zebrafish larvae, with six experimental replicates for each endpoint. Eleven targeted genes were selected according to their association with stress-axis and immediate early response class of genes. Hydrocortisone (CORT)and dexamethasone (DEX) were used as positive and negative controls, respectively. All measurements were done in two unstressed and stressed condition using standardized net handling as the stressor. A significant positive linear correlation between cortisol levels and eGFP mRNA levels was observed (r> 0.9). Based on eGFP mRNA levels in unstressed and stressed larvae two predictive models were trained (Random Forest and Logistic Regression). Both these models could correctly predict the blunted stress response upon exposure to BPA, VIN, FLX and the negative control, DEX. The negative predictive value (NPV) of these models were 100%. Similar NPV was observed when the predictive models trained based on the mRNA levels of the eleven assessed genes. Measurement of whole-body fluorescence intensity signal was not significant to detect blunted stress response. Our findings support the use of SR4G transgenic larvae as an in vivo biomonitoring model to screen chemicals for their stress-disrupting potentials. This is important because there is increasing evidence that brief exposures to environmental pollutants modify the stress response and critical coping behaviors for several generations.

2008 ◽  
Vol 68 (4) ◽  
pp. 572-578 ◽  
Author(s):  
R H Straub ◽  
G Pongratz ◽  
H Hirvonen ◽  
T Pohjolainen ◽  
M Mikkelsson ◽  
...  

Objective:Acute stress in patients with rheumatoid arthritis (RA) should stimulate a strong stress response. After cryotherapy, we expected to observe an increase of hormones of the adrenal gland and the sympathetic nervous system.Methods:A total of 55 patients with RA were recruited for whole-body cryotherapy at −110°C and −60°C, and local cold therapy between −20°C and −30°C for 7 days. We measured plasma levels of steroid hormones, neuropeptide Y (sympathetic marker), and interleukin (IL)6 daily before and after cryotherapy.Results:In both therapy groups with/without glucocorticoids (GC), hormone and IL6 levels at baseline and 5 h after cold stress did not change over 7 days of cryotherapy. In patients without GC, plasma levels of cortisol and androstenedione were highest after −110°C cold stress followed by −60°C or local cold stress. The opposite was found in patients under GC therapy, in whom, unexpectedly, −110°C cold stress elicited the smallest responses. In patients without GC, adrenal cortisol production increased relative to other adrenal steroids, and again the opposite was seen under GC therapy with a loss of cortisol and an increase of dehydroepiandrosterone. Importantly, there was no sympathetic stress response in both groups. Patients without GC and −110°C cold stress demonstrated higher plasma IL6 compared to the other treatment groups (not observed under GC), but they showed the best clinical response.Conclusions:We detected an inadequate stress response in patients with GC. It is further shown that the sympathetic stress response was inadequate in patients with/without GC. Paradoxically, plasma levels of IL6 increased under strong cold stress in patients without GC. These findings confirm dysfunctional stress axes in RA.


2005 ◽  
Vol 93 (5) ◽  
pp. 2849-2855 ◽  
Author(s):  
Erwin H. van den Burg ◽  
Ronald R. Peeters ◽  
Marleen Verhoye ◽  
Johannes Meek ◽  
Gert Flik ◽  
...  

Spatial and temporal ambient temperature variations directly influence cellular biochemistry and thus the physiology of ectotherms. However, many aquatic ectothermic species maintain coordinated sensorimotor function during large acute body-temperature changes, which points to a compensatory mechanism within the neural system. Here we used high-resolution functional magnetic resonance imaging to study brain responses to a drop of 10°C of ambient water temperature in common carp. We observed a strong drainage of blood out of the brain as of 90 s after the onset of the temperature drop, which would be expected to reduce entry of cold blood arriving from the gills so that the change in brain temperature would be slower. Although oxygen content in the brain thus decreased, we still found specific activation in the preoptic area (involved in temperature detection and stress responses), the pituitary pars distalis (stress response), and inactivation of the anterior part of the midbrain tegmentum and the pituitary pars intermedia. We propose that the blood drainage from the brain slows down the cooling of the brain during an acute temperature drop. This could help to maintain proper brain functioning including sensorimotor activity, initiation of the stress response, and the subsequent behavioral responses.


2014 ◽  
Vol 12 (3) ◽  
pp. 623-628 ◽  
Author(s):  
Janessa S. Abreu ◽  
Richard P. Brinn ◽  
Levy C. Gomes ◽  
Dawn Michelle McComb ◽  
Bernardo Baldisserotto ◽  
...  

We investigated the use of beta 1,3 glucan as an imunostimulant during a transport experiment to determine the effects upon the stress response of the pencilfish (Nannostomus trifasciatus). Pencilfish were fed for seven days with different concentrations of beta 1,3 glucan: 0.0% (control); 0.01%; 0.1% and 0.5% of beta 1,3 glucan per kg of feed-1. Fish were then transported for 24 hours by boat from Barcelos to Manaus. The highest dose of beta 1,3 glucan in the food increased Na+influx after 12 hours of transport and 0.1 and 0.5% beta 1,3 glucan maintained the flux of both ions close to zero at 24 hours. All doses of beta 1,3 glucan reduced K+ loss significantly in the beginning of the transport, but after 12 to 24 hours did not. No significant differences in whole body cortisol or survival were observed. Our results indicate that pencilfish had ionic alterations during transport from Barcelos to Manaus. The lack of significant differences in whole body cortisol and survival rate in addition to the maintenance of Na+ and K+ balance during transport reinforce the positive effects of beta 1,3 glucan immunostimulant on fish homeostasis. Therefore, we recommend its addition to food prior to transport.


2005 ◽  
Vol 71 (11) ◽  
pp. 6831-6837 ◽  
Author(s):  
Roberto Pérez-Torrado ◽  
Jose M. Bruno-Bárcena ◽  
Emilia Matallana

ABSTRACT Physiological capabilities and fermentation performance of Saccharomyces cerevisiae strains to be employed during industrial wine fermentations are critical for the quality of the final product. During the process of biomass propagation, yeast cells are dynamically exposed to a mixed and interrelated group of known stresses such as osmotic, oxidative, thermic, and/or starvation. These stressing conditions can dramatically affect the parameters of the fermentation process and the technological abilities of the yeast, e.g., the biomass yield and its fermentative capacity. Although a good knowledge exists of the behavior of S. cerevisiae under laboratory conditions, insufficient knowledge is available about yeast stress responses under the specific media and growth conditions during industrial processes. We performed growth experiments using bench-top fermentors and employed a molecular marker approach (changes in expression levels of five stress-related genes) to investigate how the cells respond to environmental changes during the process of yeast biomass production. The data show that in addition to the general stress response pathway, using the HSP12 gene as a marker, other specific stress response pathways were induced, as indicated by the changes detected in the mRNA levels of two stress-related genes, GPD1 and TRX2. These results suggest that the cells were affected by osmotic and oxidative stresses, demonstrating that these are the major causes of the stress response throughout the process of wine yeast biomass production.


2020 ◽  
Vol 29 ◽  
pp. 93-103 ◽  
Author(s):  
E Staaterman ◽  
AJ Gallagher ◽  
PE Holder ◽  
CH Reid ◽  
AH Altieri ◽  
...  

Aquatic anthropogenic noise is on the rise, with growing concern about its impact on species that are sensitive to low-frequency sounds (e.g. most fish and invertebrates). We investigated whether the reef fish Halichoeres bivittatus living in both noisy and quiet areas had differing levels of baseline stress (measured as whole-body cortisol) and whether they would exhibit a physiological stress response when exposed to boat noise playbacks. While the playback experiments significantly increased cortisol levels in fish from our experiment compared to baseline levels, there were minimal pairwise differences across treatments and no difference in baseline stress for fish living in noisy vs. quiet areas. These results may be explained by low overall auditory sensitivity, habituation to a fairly noisy environment (due to biological sounds), or that boat noise simply may not represent an immediate threat to survival in this species. These findings contrast recent studies that have shown elevated stress responses in fishes when exposed to boat noise and highlights that inter-specific differences must be considered when evaluating potential impacts of anthropogenic noise on marine life.


2019 ◽  
Vol 20 (22) ◽  
pp. 5628 ◽  
Author(s):  
Hnin Phyu Lwin ◽  
Yong-Ho Choi ◽  
Min-Woo Lee ◽  
Jae-Hyuk Yu ◽  
Kwang-Soo Shin

The regulator of G-protein signaling (RGS) proteins play an important role in upstream control of heterotrimeric G-protein signaling pathways. In the genome of the human opportunistic pathogenic fungus Aspergillus fumigatus, six RGS protein-encoding genes are present. To characterize the rgsA gene predicted to encode a protein with an RGS domain, we generated an rgsA null mutant and observed the phenotypes of the mutant. The deletion (Δ) of rgsA resulted in increased radial growth and enhanced asexual sporulation in both solid and liquid culture conditions. Accordingly, transcripts levels of the key asexual developmental regulators abaA, brlA, and wetA are elevated in the ΔrgsA mutant. Moreover, ΔrgsA resulted in elevated spore germination rates in the absence of a carbon source. The activity of cAMP-dependent protein kinase A (PKA) and mRNA levels of genes encoding PKA signaling elements are elevated by ΔrgsA. In addition, mRNA levels of genes associated with stress-response signaling increased with the lack of rgsA, and the ΔrgsA spores showed enhanced tolerance against oxidative stressors. Comparative transcriptomic analyses revealed that the ΔrgsA mutant showed higher mRNA levels of gliotoxin (GT) biosynthetic genes. Accordingly, the rgsA null mutant exhibited increased production of GT and elevated virulence in the mouse. Conversely, the majority of genes encoding glucan degrading enzymes were down-regulated by ΔrgsA, and endoglucanase activities were reduced. In summary, RgsA plays multiple roles, governing growth, development, stress responses, virulence, and external polymer degradation—likely by attenuating PKA signaling.


Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 99
Author(s):  
Shweta Devi ◽  
Vijay Kumar ◽  
Sandeep Kumar Singh ◽  
Ashish Kant Dubey ◽  
Jong-Joo Kim

Neurodegenerative disorders, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), are the most concerning disorders due to the lack of effective therapy and dramatic rise in affected cases. Although these disorders have diverse clinical manifestations, they all share a common cellular stress response. These cellular stress responses including neuroinflammation, oxidative stress, proteotoxicity, and endoplasmic reticulum (ER)-stress, which combats with stress conditions. Environmental stress/toxicity weakened the cellular stress response which results in cell damage. Small molecules, such as flavonoids, could reduce cellular stress and have gained much attention in recent years. Evidence has shown the potential use of flavonoids in several ways, such as antioxidants, anti-inflammatory, and anti-apoptotic, yet their mechanism is still elusive. This review provides an insight into the potential role of flavonoids against cellular stress response that prevent the pathogenesis of neurodegenerative disorders.


2021 ◽  
Vol 9 (6) ◽  
pp. 1116
Author(s):  
Laurens Maertens ◽  
Pauline Cherry ◽  
Françoise Tilquin ◽  
Rob Van Houdt ◽  
Jean-Yves Matroule

Bacteria encounter elevated copper (Cu) concentrations in multiple environments, varying from mining wastes to antimicrobial applications of copper. As the role of the environment in the bacterial response to Cu ion exposure remains elusive, we used a tagRNA-seq approach to elucidate the disparate responses of two morphotypes of Caulobacter crescentus NA1000 to moderate Cu stress in a complex rich (PYE) medium and a defined poor (M2G) medium. The transcriptome was more responsive in M2G, where we observed an extensive oxidative stress response and reconfiguration of the proteome, as well as the induction of metal resistance clusters. In PYE, little evidence was found for an oxidative stress response, but several transport systems were differentially expressed, and an increased need for histidine was apparent. These results show that the Cu stress response is strongly dependent on the cellular environment. In addition, induction of the extracytoplasmic function sigma factor SigF and its regulon was shared by the Cu stress responses in both media, and its central role was confirmed by the phenotypic screening of a sigF::Tn5 mutant. In both media, stalked cells were more responsive to Cu stress than swarmer cells, and a stronger basal expression of several cell protection systems was noted, indicating that the swarmer cell is inherently more Cu resistant. Our approach also allowed for detecting several new transcription start sites, putatively indicating small regulatory RNAs, and additional levels of Cu-responsive regulation.


2021 ◽  
Vol 72 (8) ◽  
pp. 3294-3306
Author(s):  
Ariel M Hughes ◽  
H Tucker Hallmark ◽  
Lenka Plačková ◽  
Ondrej Novák ◽  
Aaron M Rashotte

Abstract Cytokinin response factors (CRFs) are transcription factors that are involved in cytokinin (CK) response, as well as being linked to abiotic stress tolerance. In particular, oxidative stress responses are activated by Clade III CRF members, such as AtCRF6. Here we explored the relationships between Clade III CRFs and oxidative stress. Transcriptomic responses to oxidative stress were determined in two Clade III transcription factors, Arabidopsis AtCRF5 and tomato SlCRF5. AtCRF5 was required for regulated expression of >240 genes that are involved in oxidative stress response. Similarly, SlCRF5 was involved in the regulated expression of nearly 420 oxidative stress response genes. Similarities in gene regulation by these Clade III members in response to oxidative stress were observed between Arabidopsis and tomato, as indicated by Gene Ontology term enrichment. CK levels were also changed in response to oxidative stress in both species. These changes were regulated by Clade III CRFs. Taken together, these findings suggest that Clade III CRFs play a role in oxidative stress response as well as having roles in CK signaling.


Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 266
Author(s):  
Chiara Lanzillotta ◽  
Fabio Di Domenico

Down syndrome (DS) is the most common genomic disorder characterized by the increased incidence of developing early Alzheimer’s disease (AD). In DS, the triplication of genes on chromosome 21 is intimately associated with the increase of AD pathological hallmarks and with the development of brain redox imbalance and aberrant proteostasis. Increasing evidence has recently shown that oxidative stress (OS), associated with mitochondrial dysfunction and with the failure of antioxidant responses (e.g., SOD1 and Nrf2), is an early signature of DS, promoting protein oxidation and the formation of toxic protein aggregates. In turn, systems involved in the surveillance of protein synthesis/folding/degradation mechanisms, such as the integrated stress response (ISR), the unfolded stress response (UPR), and autophagy, are impaired in DS, thus exacerbating brain damage. A number of pre-clinical and clinical studies have been applied to the context of DS with the aim of rescuing redox balance and proteostasis by boosting the antioxidant response and/or inducing the mechanisms of protein re-folding and clearance, and at final of reducing cognitive decline. So far, such therapeutic approaches demonstrated their efficacy in reverting several aspects of DS phenotype in murine models, however, additional studies aimed to translate these approaches in clinical practice are still needed.


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