scholarly journals Integrated Hypoxia Signaling and Oxidative Stress in Developmental Neurotoxicity of Benzo[a]Pyrene in Zebrafish Embryos

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 731 ◽  
Author(s):  
Yi-Chen Lin ◽  
Chang-Yi Wu ◽  
Chin-Hwa Hu ◽  
Tun-Wen Pai ◽  
Yet-Ran Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Target Genes ◽  
Neuronal Development ◽  
Posterior Commissure ◽  
Zebrafish Model ◽  
Embryonic Exposure ◽  
Ventral Thalamus ◽  
Polycyclic Aromatic ◽  
Transcriptional Changes ◽  
And Function

Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon formed by the incomplete combustion of organic matter. Environmental B[a]P contamination poses a serious health risk to many organisms because the pollutant may negatively affect many physiological systems. As such, chronic exposure to B[a]P is known to lead to locomotor dysfunction and neurodegeneration in several organisms. In this study, we used the zebrafish model to delineate the acute toxic effects of B[a]P on the developing nervous system. We found that embryonic exposure of B[a]P downregulates shh and isl1, causing morphological hypoplasia in the telencephalon, ventral thalamus, hypothalamus, epiphysis and posterior commissure. Moreover, hypoxia-inducible factors (hif1a and hif2a) are repressed upon embryonic exposure of B[a]P, leading to reduced expression of the Hif-target genes, epo and survivin, which are associated with neural differentiation and maintenance. During normal embryogenesis, low-level oxidative stress regulates neuronal development and function. However, our experiments revealed that embryonic oxidative stress is greatly increased in B[a]P-treated embryos. The expression of catalase was decreased and sod1 expression increased in B[a]P-treated embryos. These transcriptional changes were coincident with increased embryonic levels of H2O2 and malondialdehyde, with the levels in B[a]P-treated fish similar to those in embryos treated with 120-μM H2O2. Together, our data suggest that reduced Hif signaling and increased oxidative stress are involved in B[a]P-induced acute neurotoxicity during embryogenesis.

scholarly journals Oxidative Stress-Related Mechanisms in Schizophrenia Pathogenesis and New Treatment Perspectives

2021 ◽  
Vol 2021 ◽  
pp. 1-37
Author(s):  
Evgeny A. Ermakov ◽  
Elena M. Dmitrieva ◽  
Daria A. Parshukova ◽  
Daria V. Kazantseva ◽  
Alisa R. Vasilieva ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neuronal Development ◽  
Clinical Manifestations ◽  
Cellular Level ◽  
Transcriptional Factors ◽  
Great Promise ◽  
Redox Imbalance ◽  
New Treatment ◽  
And Function ◽  
Glutathione Deficiency

Schizophrenia is recognized to be a highly heterogeneous disease at various levels, from genetics to clinical manifestations and treatment sensitivity. This heterogeneity is also reflected in the variety of oxidative stress-related mechanisms contributing to the phenotypic realization and manifestation of schizophrenia. At the molecular level, these mechanisms are supposed to include genetic causes that increase the susceptibility of individuals to oxidative stress and lead to gene expression dysregulation caused by abnormal regulation of redox-sensitive transcriptional factors, noncoding RNAs, and epigenetic mechanisms favored by environmental insults. These changes form the basis of the prooxidant state and lead to altered redox signaling related to glutathione deficiency and impaired expression and function of redox-sensitive transcriptional factors (Nrf2, NF-κB, FoxO, etc.). At the cellular level, these changes lead to mitochondrial dysfunction and metabolic abnormalities that contribute to aberrant neuronal development, abnormal myelination, neurotransmitter anomalies, and dysfunction of parvalbumin-positive interneurons. Immune dysfunction also contributes to redox imbalance. At the whole-organism level, all these mechanisms ultimately contribute to the manifestation and development of schizophrenia. In this review, we consider oxidative stress-related mechanisms and new treatment perspectives associated with the correction of redox imbalance in schizophrenia. We suggest that not only antioxidants but also redox-regulated transcription factor-targeting drugs (including Nrf2 and FoxO activators or NF-κB inhibitors) have great promise in schizophrenia. But it is necessary to develop the stratification criteria of schizophrenia patients based on oxidative stress-related markers for the administration of redox-correcting treatment.

scholarly journals A Zebrafish Model for Selenoprotein Synthesis and Function (OR11-01-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Paul Copeland ◽  
Michael Vetick
Keyword(s):  
Oxidative Stress ◽  
Rna Binding ◽  
Binding Protein ◽  
Model System ◽  
National Institutes Of Health ◽  
Zebrafish Model ◽  
Funding Sources ◽  
And Function ◽  
Selenoprotein Mrnas

Abstract Objectives We have established a zebrafish model system that will allow unprecedented access to the role of selenoprotein function during development. The work described here focuses on a poorly characterized RNA binding protein that is similar to SECIS binding protein 2 (SBP2), which is required for the co-translational insertion of selenocysteine at select UGA codons in selenoprotein mRNAs. This protein, SECISBP2L, shares many features with SBP2 but is has no known function. We hypothesize that the zebrafish model system will reveal a selenoprotein-synthesis related function for SECISBP2L. Methods Using CRISPR/Cas9, we generated zebrafish with a disruption in one of the conserved domains in SECISBP2L. When bred out to a homozygous mutant animal, we verified that SECISBP2L protein expression was eliminated. To analyze selenoprotein synthesis, we metabolically labeled wild-type and mutant embryos with radioactive selenium (Se-75). Results In terms of overt phenotypes in SECISBP2L null fish, we observed no defects in growth, mobility or fertility. However, we noticed a significant sensitivity to oxidative stress as measured by lethality associated with peroxide exposure. In order to detect changes in selenoprotein expression that may have resulted from SECISBP2L loss, we performed Se-75 labeling in embryos. We also began an investigation of the effect of oxidative stress on selenoprotein expression during development. As such, one set of embryos was treated for 24 hours with 100 nM Se-75 and the other with Se-75 plus 200 μM H2O2. In general, we did not observe an overall alteration of selenoprotein expression as a result of SECISBP2L loss. We did, however, observe a significant spike of expression for a 50 kDa selenoprotein that did not occur in the SECISBP2L null animals. Based on this molecular weight, we predict that this band corresponds to selenophosphate synthase (SEPHS2). In addition, subsequent labeling at later time points revealed a general reduction of selenoprotein expression that may result from reduced SEPHS2 expression because it is essential for selenocysteine-tRNA synthesis. Conclusions We conclude that SECISBP2L is required for optimal selenoprotein expression and its function may be induced by oxidative stress. We have also demonstrated the value of a zebrafish model system for studying the mechanism of selenoprotein synthesis. Funding Sources Funded by the National Institutes of Health.

scholarly journals Use of Oxidative Stress Responses to Determine the Efficacy of Inactivation Treatments on Cryptosporidium Oocysts

2021 ◽  
Vol 9 (7) ◽  
pp. 1463
Author(s):  
Tamirat Tefera Temesgen ◽  
Kristoffer Relling Tysnes ◽  
Lucy Jane Robertson
Keyword(s):  
Oxidative Stress ◽  
Stress Responses ◽  
Target Genes ◽  
Cryptosporidium Oocyst ◽  
Drinking Water Treatment ◽  
Proof Of Concept ◽  
Environmental Matrices ◽  
Oocyst Wall ◽  
Novel Approach ◽  
Cryptosporidium Oocysts

Cryptosporidium oocysts are known for being very robust, and their prolonged survival in the environment has resulted in outbreaks of cryptosporidiosis associated with the consumption of contaminated water or food. Although inactivation methods used for drinking water treatment, such as UV irradiation, can inactivate Cryptosporidium oocysts, they are not necessarily suitable for use with other environmental matrices, such as food. In order to identify alternative ways to inactivate Cryptosporidium oocysts, improved methods for viability assessment are needed. Here we describe a proof of concept for a novel approach for determining how effective inactivation treatments are at killing pathogens, such as the parasite Cryptosporidium. RNA sequencing was used to identify potential up-regulated target genes induced by oxidative stress, and a reverse transcription quantitative PCR (RT-qPCR) protocol was developed to assess their up-regulation following exposure to different induction treatments. Accordingly, RT-qPCR protocols targeting thioredoxin and Cryptosporidium oocyst wall protein 7 (COWP7) genes were evaluated on mixtures of viable and inactivated oocysts, and on oocysts subjected to various potential inactivation treatments such as freezing and chlorination. The results from the present proof-of-concept experiments indicate that this could be a useful tool in efforts towards assessing potential technologies for inactivating Cryptosporidium in different environmental matrices. Furthermore, this approach could also be used for similar investigations with other pathogens.

scholarly journals 145 President Oral Presentation Pick: Prenatal stress increases skeletal muscle mitochondrial volume density and function in yearling Brahman calves

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 120-121
Author(s):  
Chloey P Guy ◽  
Catherine L Wellman ◽  
David G Riley ◽  
Charles R Long ◽  
Ron D Randel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Creatine Kinase ◽  
Muscle Damage ◽  
Prenatal Stress ◽  
Citrate Synthase ◽  
Volume Density ◽  
Assembly Factor ◽  
Mitochondrial Volume ◽  
Mitochondrial Volume Density ◽  
And Function

Abstract We previously determined that prenatal stress (PNS) differentially affected methylation of DNA from leukocytes of 28-d-old calves. Specifically, COX14 (cytochrome c oxidase (COX) assembly factor) and CKMT1B (mitochondrial creatine kinase U-type) were hypomethylated and COA5 (COX assembly factor 5), COX5A (COX subunit 5A), NRF1 (nuclear respiratory factor 1), and GSST1 (glutathione S-transferase theta-1) were hypermethylated in PNS compared to non-PNS calves (P ≤ 0.05). Our current objective was to test the hypothesis that PNS exhibit impaired mitochondrial function and greater oxidative stress than non-PNS calves. Blood and longissimus dorsi muscle samples were collected from yearling Brahman calves whose mothers were stressed by 2 h transportation at 60, 80, 100, 120, and 140 days of gestation (PNS; 8 bulls, 6 heifers) and non-PNS calves (4 bulls, 6 heifers). Serum was evaluated for the stress hormone, cortisol, and muscle damage marker, creatine kinase; muscle was analyzed for mitochondrial volume density and function by citrate synthase (CS) and COX activities, respectively, concentration of malondialdehyde, a lipid peroxidation marker, and activity of the antioxidant, superoxide dismutase (SOD). Data were analyzed using mixed linear models with treatment and sex as fixed effects. Serum cortisol was numerically higher in PNS than non-PNS calves but was not statistically different. Muscle CS and COX activities relative to protein were greater in PNS than non-PNS calves (P ≤ 0.03), but COX relative to CS activity was similar between groups. Activity of COX was greater in bulls than heifers (P = 0.03), but no other measure was affected by sex. All other measures were unaffected by PNS. Prenatal stress did not affect markers of muscle damage and oxidative stress in yearling Brahman calves at rest but mitochondrial volume density and function were greater in PNS calves. Acute stressors induce oxidative stress, so implications of differences in mitochondria in PNS calves following a stressor should be investigated.

scholarly journals Modulation of Innate Immune Toxicity by Silver Nanoparticle Exposure and the Preventive Effects of Pterostilbene

2021 ◽  
Vol 22 (5) ◽  
pp. 2536
Author(s):  
Rong-Jane Chen ◽  
Chiao-Ching Huang ◽  
Rosita Pranata ◽  
Yu-Hsuan Lee ◽  
Yu-Ying Chen ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Good Alternative ◽  
Innate Immune ◽  
Toxic Effects ◽  
Transgenic Zebrafish ◽  
Zebrafish Model ◽  
Cytokines And Chemokines ◽  
Living Organisms ◽  
And Function ◽  
Immune Toxicity

Silver nanoparticles pose a potential risk to ecosystems and living organisms due to their widespread use in various fields and subsequent gradual release into the environment. Only a few studies have investigated the effects of silver nanoparticles (AgNPs) toxicity on immunological functions. Furthermore, these toxic effects have not been fully explored. Recent studies have indicated that zebrafish are considered a good alternative model for testing toxicity and for evaluating immunological toxicity. Therefore, the purpose of this study was to investigate the toxicity effects of AgNPs on innate immunity using a zebrafish model and to investigate whether the natural compound pterostilbene (PTE) could provide protection against AgNPs-induced immunotoxicity. Wild type and neutrophil- and macrophage-transgenic zebrafish lines were used in the experiments. The results indicated that the exposure to AgNPs induced toxic effects including death, malformation and the innate immune toxicity of zebrafish. In addition, AgNPs affect the number and function of neutrophils and macrophages. The expression of immune-related cytokines and chemokines was also affected. Notably, the addition of PTE could activate immune cells and promote their accumulation in injured areas in zebrafish, thereby reducing the damage caused by AgNPs. In conclusion, AgNPs may induce innate immune toxicity and PTE could ameliorate this toxicity.

scholarly journals Activation of the p11/SMARCA3/Neurensin-2 pathway in parvalbumin interneurons mediates the response to chronic antidepressants

2021 ◽  
Author(s):  
Gali Umschweif ◽  
Lucian Medrihan ◽  
Kathryn A. McCabe ◽  
Yotam Sagi ◽  
Paul Greengard
Keyword(s):  
Chromatin Remodeling ◽  
Behavioral Response ◽  
Hippocampal Neurons ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Chronic Treatment ◽  
Target Genes ◽  
Delayed Response ◽  
Dynamic Changes ◽  
Parvalbumin Interneurons ◽  
Transcriptional Changes

AbstractThe delayed behavioral response to chronic antidepressants depends on dynamic changes in the hippocampus. It was suggested that the antidepressant protein p11 and the chromatin remodeling factor SMARCA3 mediate this delayed response by inducing transcriptional changes in hippocampal neurons. However, what target genes are regulated by the p11/SMARCA3 complex to mediate the behavioral response to antidepressants, and what cell type mediates these molecular changes remain unknown. Here we report that the p11/SMARCA3 complex represses Neurensin-2 transcription in hippocampal parvalbumin-expressing interneurons after chronic treatment with Selective Serotonin Reuptake Inhibitors (SSRI). The behavioral response to antidepressants requires upregulation of p11, accumulation of SMARCA3 in the cell nucleus, and a consequent repression of Neurensin-2 transcription in these interneurons. We elucidate a functional role for p11/SMARCA3/Neurensin-2 pathway in regulating AMPA-receptor signaling in parvalbumin-expressing interneurons, a function that is enhanced by chronic treatment with SSRIs. These results link SSRIs to dynamic glutamatergic changes and implicate p11/SMARCA3/Neurensin-2 pathway in the development of more specific and efficient therapeutic strategies for neuropsychiatric disorders.

Sign in / Sign up

Export Citation Format

Share Document