Nitroreductase increases menadione-mediated oxidative stress in Aspergillus nidulans

2021 ◽  
Author(s):  
Yao Zhou ◽  
Hangya Lv ◽  
Haoxiang Li ◽  
Jingyi Li ◽  
Yunfeng Yan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Aspergillus Nidulans ◽  
Stress Responses ◽  
Reduction Reaction ◽  
Single Electron ◽  
Wide Range ◽  
Ros Scavenger ◽  
Electron Reduction ◽  
The Relationship

Nitroreductases (NTRs) catalyze the reduction of a wide range of nitro-compounds and quinones using NAD(P)H. Although the physiological functions of these enzymes remain obscure, a tentative function of resistance to reactive oxygen species (ROS) via the detoxification of menadione has been proposed. This suggestion is based primarily on the transcriptional or translational induction of an NTR response to menadione, rather than on convincing experimental evidence. We investigated the performance of a fungal NTR from Aspergillus nidulans (AnNTR) exposed to menadione, to address the question of whether NTR is really a ROS defense enzyme. We confirmed that AnNTR was transcriptionally induced by external menadione. We observed that menadione treatment generated cytotoxic levels of O 2 •− , which requires well-known antioxidant enzymes such as superoxide dismutase, catalase, and peroxiredoxin, to protect A. nidulans against menadione-derived ROS stress. However, AnNTR was counterproductive for ROS defense, since knocking out AnNTR decreased the intracellular O 2 •− levels, resulting in fungal viability higher than that of the wild type. This observation implies that AnNTR may accelerate the generation of O 2 •− from menadione. Our in vitro experiments indicated that AnNTR uses NADPH to reduce menadione in a single-electron reaction, and the subsequent semiquinone-quinone redox cycling resulted in O 2 •− generation. We demonstrated that A. nidulans nitroreductase should be a ROS generator, but not a ROS scavenger, in the presence of menadione. Our results clarified the relationship between nitroreductase and menadione-derived ROS stress, which has long been ambiguous. Importance Menadione is commonly used as an O 2 •− generator in studies into oxidative stress responses. However, the precise mechanism through which menadione mediates cellular O 2 •− generation, and the way in which cells respond, remains unclear. Elucidating these events will have important implications for the use of menadione in biological and medical studies. Our results show that the production of Aspergillus nidulans nitroreductase (AnNTR) was induced by menadione. However, the accumulated AnNTR did not protect cells, but instead increased the cytotoxic effect of menadione, through a single-electron reduction reaction. Our finding that nitroreductase is involved in the menadione-mediated O 2 •− generation pathway has clarified the relationship between nitroreductase and menadione-derived ROS stress, which has long been ambiguous.

scholarly journals Inositol phosphates: health implications, methods of analysis, and occurrence in plant foods

2018 ◽  
Vol 1 ◽  
Author(s):  
Quynh H. Duong ◽  
Karen G. Lapsley ◽  
Ronald B. Pegg
Keyword(s):  
Inositol Phosphates ◽  
Negative Effects ◽  
Plant Foods ◽  
Plant Seeds ◽  
Cell Functions ◽  
Wide Range ◽  
Multiple Cell ◽  
The Relationship

Inositol phosphates (InsPs), especially myo-inositol hexakisphosphate (InsP6), are important binders of phosphorus and minerals in plant seeds. However, they have long been considered as anti-nutritional components of plant foods due to their possible negative effects on the absorption of minerals and proteins in mammals. On the other hand, recent findings have found InsPs to be ubiquitous in eukaryote cells and actively participating in multiple cell functions. In vivo and in vitro studies have also documented the preventive potential of these compounds against the development of a wide range of diseases. In light of these findings, interest in the relationship between these compounds and human health has been renewed. It is suggested that the interactions of InsPs with other nutrients in the gut are complex, that the absorption of dietary InsPs might be implied but is not certain, and that the disease fighting capabilities of InsPs hold both promises and limitations. At the same time, the analysis of these compounds in foods and biological samples still faces many challenges, calling for more advanced modification and developments in the future.

scholarly journals Crosstalk between Oxidative Stress and Inflammatory Liver Injury in the Pathogenesis of Alcoholic Liver Disease

2022 ◽  
Vol 23 (2) ◽  
pp. 774
Author(s):  
Yoon Mee Yang ◽  
Ye Eun Cho ◽  
Seonghwan Hwang
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Alcoholic Liver Disease ◽  
Inflammatory Responses ◽  
Tissue Injury ◽  
Pathological Features ◽  
Excessive Alcohol Consumption ◽  
Excessive Alcohol ◽  
The Relationship

Alcoholic liver disease (ALD) is characterized by the injury, inflammation, and scarring in the liver owing to excessive alcohol consumption. Currently, ALD is a leading cause for liver transplantation. Therefore, extensive studies (in vitro, in experimental ALD models and in humans) are needed to elucidate pathological features and pathogenic mechanisms underlying ALD. Notably, oxidative changes in the liver have been recognized as a signature trait of ALD. Progression of ALD is linked to the generation of highly reactive free radicals by reactions involving ethanol and its metabolites. Furthermore, hepatic oxidative stress promotes tissue injury and, in turn, stimulates inflammatory responses in the liver, forming a pathological loop that promotes the progression of ALD. Accordingly, accumulating further knowledge on the relationship between oxidative stress and inflammation may help establish a viable therapeutic approach for treating ALD.

Possible Effects of Depolarizing GABAA Conductance on the Neuronal Input–Output Relationship: A Modeling Study

2005 ◽  
Vol 93 (6) ◽  
pp. 3504-3523 ◽  
Author(s):  
Kenji Morita ◽  
Kunichika Tsumoto ◽  
Kazuyuki Aihara
Keyword(s):  
Firing Rate ◽  
Cortical Neurons ◽  
Reversal Potential ◽  
Pyramidal Cells ◽  
Resting Potential ◽  
Input Output ◽  
Wide Range ◽  
The Relationship

Recent in vitro experiments revealed that the GABAA reversal potential is about 10 mV higher than the resting potential in mature mammalian neocortical pyramidal cells; thus GABAergic inputs could have facilitatory, rather than inhibitory, effects on action potential generation under certain conditions. However, how the relationship between excitatory input conductances and the output firing rate is modulated by such depolarizing GABAergic inputs under in vivo circumstances has not yet been understood. We examine herewith the input–output relationship in a simple conductance-based model of cortical neurons with the depolarized GABAA reversal potential, and show that a tonic depolarizing GABAergic conductance up to a certain amount does not change the relationship between a tonic glutamatergic driving conductance and the output firing rate, whereas a higher GABAergic conductance prevents spike generation. When the tonic glutamatergic and GABAergic conductances are replaced by in vivo–like highly fluctuating inputs, on the other hand, the effect of depolarizing GABAergic inputs on the input–output relationship critically depends on the degree of coincidence between glutamatergic input events and GABAergic ones. Although a wide range of depolarizing GABAergic inputs hardly changes the firing rate of a neuron driven by noncoincident glutamatergic inputs, a certain range of these inputs considerably decreases the firing rate if a large number of driving glutamatergic inputs are coincident with them. These results raise the possibility that the depolarized GABAA reversal potential is not a paradoxical mystery, but is instead a sophisticated device for discriminative firing rate modulation.

scholarly journals Small extracellular vesicles convey the stress-induced adaptive responses of melanoma cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Maria Harmati ◽  
Edina Gyukity-Sebestyen ◽  
Gabriella Dobra ◽  
Laszlo Janovak ◽  
Imre Dekany ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Extracellular Vesicles ◽  
Stress Responses ◽  
In Silico ◽  
Specific Response ◽  
Response Patterns ◽  
Adaptive Responses ◽  
Mediated Communication ◽  
Ki 67

Abstract Exosomes are small extracellular vesicles (sEVs), playing a crucial role in the intercellular communication in physiological as well as pathological processes. Here, we aimed to study whether the melanoma-derived sEV-mediated communication could adapt to microenvironmental stresses. We compared B16F1 cell-derived sEVs released under normal and stress conditions, including cytostatic, heat and oxidative stress. The miRNome and proteome showed substantial differences across the sEV groups and bioinformatics analysis of the obtained data by the Ingenuity Pathway Analysis also revealed significant functional differences. The in silico predicted functional alterations of sEVs were validated by in vitro assays. For instance, melanoma-derived sEVs elicited by oxidative stress increased Ki-67 expression of mesenchymal stem cells (MSCs); cytostatic stress-resulted sEVs facilitated melanoma cell migration; all sEV groups supported microtissue generation of MSC-B16F1 co-cultures in a 3D tumour matrix model. Based on this study, we concluded that (i) molecular patterns of tumour-derived sEVs, dictated by the microenvironmental conditions, resulted in specific response patterns in the recipient cells; (ii) in silico analyses could be useful tools to predict different stress responses; (iii) alteration of the sEV-mediated communication of tumour cells might be a therapy-induced host response, with a potential influence on treatment efficacy.

The effect of pre-ovulatory nutrition on the subsequent development of superovulated sheep ova in an in vitro culture system.

1994 ◽  
Vol 1994 ◽  
pp. 82-82
Author(s):  
J. Creed ◽  
T.G. McEvoy ◽  
J.J. Robinson ◽  
R.P. Aitken ◽  
R.M. Palmer ◽  
...  
Keyword(s):  
Food Intake ◽  
Oocyte Maturation ◽  
Culture System ◽  
Subsequent Development ◽  
Plasma Progesterone ◽  
Wide Range ◽  
In Vitro Culture System ◽  
High Level ◽  
The Relationship

Superovulatory treatments for ewes are normally preceded by a period of priming. In a recent study involving two contrasting levels of feeding (0.6 versus 2.4 x maintenance), McEvoy et al (1993) observed that the higher level of feeding suppressed pre-ovulatory plasma progesterone concentrations and the subsequent early development and viability of fertilized ova. This finding suggests that there is a need to reconsider the recommendation, based on data for spontaneously-ovulating ewes, that ‘superovulated embryo donor ewes’ should be maintained on a high level of feeding during the period of oocyte maturation. It also raises questions regarding the form of the relationship between food intake and plasma progesterone concentrations over the wide range of feeding levels that occur in practice. The aims of the present study were therefore two-fold; firstly, to investigate the relationship between level of feeding and plasma progesterone for feed intakes that ranged from 0.6 x maintenance (M) to 2.4 M and secondly to assess the effect of pre-ovulatory feeding levels on the number, quality and viability of ova produced following superovulation.

scholarly journals Protective Effect of Coconut Oil Meal Phenolic Antioxidants against Macromolecular Damage: In Vitro and In Vivo Study

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
A. N. Karunasiri ◽  
C. M. Senanayake ◽  
H. Hapugaswatta ◽  
N. Jayathilaka ◽  
K. N. Seneviratne
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Stress Responses ◽  
Coconut Oil ◽  
Oral Feeding ◽  
Phenolic Antioxidants ◽  
Significant Difference ◽  
Macromolecular Damage

Coconut oil meal, a cheap by-product of coconut oil production, is a rich source of phenolic antioxidants. Many age-related diseases are caused by reactive oxygen species- (ROS-) induced damage to macromolecules such as lipids, proteins, and DNA. In the present study, the protective effect of the phenolic extract of coconut oil meal (CMPE) against macromolecular oxidative damage was evaluated using in vitro and in vivo models. Sunflower oil, bovine serum albumin (BSA), and plasmid DNA were used in the in vitro study, and thiobarbituric acid reactive substances (TBARS), protein carbonyl, and nicked DNA were evaluated as oxidation products. The inhibitory effect of CMPE against H2O2-induced macromolecular damage was evaluated using cultured HEp-2 cells. The results indicate that CMPE inhibits macromolecular damage both in vitro and in vivo. In addition, CMPE regulates redox status of HEp-2 cells under oxidative stress conditions by maintaining higher reduced glutathione levels. There was no significant difference in the expression of glutathione peroxidase in stressed and unstressed cells suggesting that CMPE regulates the cellular oxidative stress responses without affecting the expression of oxidative stress response genes. Oral feeding of Wistar rats with CMPE improves the serum and plasma antioxidant status without causing any toxic effects.

scholarly journals Transcriptome changes in undifferentiated Caco-2 cells exposed to food-grade titanium dioxide (E171): contribution of the nano- and micro- sized particles

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Héloïse Proquin ◽  
Marloes C. M. Jonkhout ◽  
Marlon J. Jetten ◽  
Henk van Loveren ◽  
Theo M. de Kok ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Titanium Dioxide ◽  
Immune System ◽  
Stress Responses ◽  
Inflammatory Responses ◽  
Relative Contribution ◽  
Immune System Activation ◽  
Favourable Environment

AbstractThe food additive titanium dioxide (TiO2), or E171, is a white food colorant. Recent studies showed after E171 ingestion a significantly increased number of colorectal tumours in a colorectal cancer mouse model as well as inflammatory responses and dysregulation of the immune system in the intestine of rats. In the mouse colon, E171 induced gene expression changes related to oxidative stress, impairment of the immune system, activation of signalling and cancer-related processes. E171 comprises nanoparticles (NPs) and microparticles (MPs). Previous in vitro studies showed that E171, NPs and MPs induced oxidative stress responses, DNA damage and micronuclei formation. This study aimed to investigate the relative contribution of the NPs and MPs to effects of E171 at the transcriptome level in undifferentiated Caco-2 cells by genome wide microarray analysis. The results showed that E171, NPs, and MPs induce gene expression changes related to signalling, inflammation, immune system, transport and cancer. At the pathway level, metabolism of proteins with the insulin processing pathway and haemostasis were specific to E171 exposure. The gene expression changes associated with the immune system and inflammation induced by E171, MPs, and NPs suggest the creation of a favourable environment for colon cancer development.

scholarly journals The transcription factor NRF2 enhances melanoma malignancy by blocking differentiation and inducing COX2 expression

Oncogene ◽  
2020 ◽  
Vol 39 (44) ◽  
pp. 6841-6855 ◽  
Author(s):  
Christina Jessen ◽  
Julia K. C. Kreß ◽  
Apoorva Baluapuri ◽  
Anita Hufnagel ◽  
Werner Schmitz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Immune Response ◽  
Transcription Factor ◽  
Prostaglandin E2 ◽  
Innate Immune Response ◽  
Stress Responses ◽  
Melanoma Cells ◽  
Innate Immune ◽  
Dependent Manner

AbstractThe transcription factor NRF2 is the major mediator of oxidative stress responses and is closely connected to therapy resistance in tumors harboring activating mutations in the NRF2 pathway. In melanoma, such mutations are rare, and it is unclear to what extent melanomas rely on NRF2. Here we show that NRF2 suppresses the activity of the melanocyte lineage marker MITF in melanoma, thereby reducing the expression of pigmentation markers. Intriguingly, we furthermore identified NRF2 as key regulator of immune-modulating genes, linking oxidative stress with the induction of cyclooxygenase 2 (COX2) in an ATF4-dependent manner. COX2 is critical for the secretion of prostaglandin E2 and was strongly induced by H2O2 or TNFα only in presence of NRF2. Induction of MITF and depletion of COX2 and PGE2 were also observed in NRF2-deleted melanoma cells in vivo. Furthermore, genes corresponding to the innate immune response such as RSAD2 and IFIH1 were strongly elevated in absence of NRF2 and coincided with immune evasion parameters in human melanoma datasets. Even in vitro, NRF2 activation or prostaglandin E2 supplementation blunted the induction of the innate immune response in melanoma cells. Transcriptome analyses from lung adenocarcinomas indicate that the observed link between NRF2 and the innate immune response is not restricted to melanoma.

Melatonin synthesis enzymes interact with ascorbate peroxidase to protect against oxidative stress in cassava

2020 ◽  
Vol 71 (18) ◽  
pp. 5645-5655 ◽  
Author(s):  
Yujing Bai ◽  
Jingru Guo ◽  
Russel J Reiter ◽  
Yunxie Wei ◽  
Haitao Shi
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Capacity ◽  
Stress Tolerance ◽  
Ascorbate Peroxidase ◽  
Stress Responses ◽  
Direct Interaction ◽  
Ros Scavenging ◽  
Melatonin Synthesis

Abstract Melatonin is an important indole amine hormone in animals and plants. The enzymes that catalyse melatonin synthesis positively regulate plant stress responses through modulation of the accumulation of reactive oxygen species (ROS). However, the relationship between melatonin biosynthetic enzymes and ROS-scavenging enzymes has not been characterized. In this study, we demonstrate that two enzymes of the melatonin synthesis pathway in Manihot esculenta (MeTDC2 and MeASMT2) directly interact with ascorbate peroxidase (MeAPX2) in both in vitro and in vivo experiments. Notably, in the presence of MeTDC2 and MeASMT2, MeAPX2 showed significantly higher activity and antioxidant capacity than the purified MeAPX2 protein alone. These findings indicate that MeTDC2–MeAPX2 and MeASMT2–MeAPX2 interactions both activate APX activity and increase antioxidant capacity. In addition, the combination of MeTDC2, MeASMT2, and MeAPX2 conferred improved resistance to hydrogen peroxide in Escherichia coli. Moreover, this combination also positively regulates oxidative stress tolerance in cassava. Taken together, these findings not only reveal a direct interaction between MeTDC2, MeASMT2, and MeAPX2, but also highlight the importance of this interaction in regulating redox homoeostasis and stress tolerance in cassava.

scholarly journals The Needs for Developing Experiments on Reservoirs in Hantavirus Research: Accomplishments, Challenges and Promises for the Future

Viruses ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 664 ◽  
Author(s):  
Madrières ◽  
Castel ◽  
Murri ◽  
Vulin ◽  
Marianneau ◽  
...  
Keyword(s):  
Evolutionary Ecology ◽  
Experimental Studies ◽  
Mortality Rates ◽  
Wide Range ◽  
The Future ◽  
The Subject ◽  
The Many ◽  
Human Infections ◽  
The Relationship

Due to their large geographic distribution and potential high mortality rates in human infections, hantaviruses constitute a worldwide threat to public health. As such, they have been the subject of a large array of clinical, virological and eco-evolutionary studies. Many experiments have been conducted in vitro or on animal models to identify the mechanisms leading to pathogenesis in humans and to develop treatments of hantavirus diseases. Experimental research has also been dedicated to the understanding of the relationship between hantaviruses and their reservoirs. However, these studies remain too scarce considering the diversity of hantavirus/reservoir pairs identified, and the wide range of issues that need to be addressed. In this review, we present a synthesis of the experimental studies that have been conducted on hantaviruses and their reservoirs. We aim at summarizing the knowledge gathered from this research, and to emphasize the gaps that need to be filled. Despite the many difficulties encountered to carry hantavirus experiments, we advocate for the need of such studies in the future, at the interface of evolutionary ecology and virology. They are critical to address emerging areas of research, including hantavirus evolution and the epidemiological consequences of individual variation in infection outcomes.

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