scholarly journals Nitric oxide and nitrosative stress tolerance in yeast

2011 ◽  
Vol 39 (1) ◽  
pp. 219-223 ◽  
Author(s):  
Anna Tillmann ◽  
Neil A.R. Gow ◽  
Alistair J.P. Brown
Keyword(s):  
Nitric Oxide ◽  
Nitrosative Stress ◽  
Binding Domain ◽  
Phagocytic Cells ◽  
Yeast Saccharomyces Cerevisiae ◽  
Pathogenic Yeast ◽  
Human Fungal Pathogen ◽  
Reactive Nitrogen Intermediates ◽  
Detoxification Mechanisms ◽  
Fad Binding

The opportunistic human fungal pathogen Candida albicans encounters diverse environmental stresses when it is in contact with its host. When colonizing and invading human tissues, C. albicans is exposed to ROS (reactive oxygen species) and RNIs (reactive nitrogen intermediates). ROS and RNIs are generated in the first line of host defence by phagocytic cells such as macrophages and neutrophils. In order to escape these host-induced oxidative and nitrosative stresses, C. albicans has developed various detoxification mechanisms. One such mechanism is the detoxification of NO (nitric oxide) to nitrate by the flavohaemoglobin enzyme CaYhb1. Members of the haemoglobin superfamily are highly conserved and are found in archaea, eukaryotes and bacteria. Flavohaemoglobins have a dioxygenase activity [NOD (NO dioxygenase domain)] and contain three domains: a globin domain, an FAD-binding domain and an NAD(P)-binding domain. In the present paper, we examine the nitrosative stress response in three fungal models: the pathogenic yeast C. albicans, the benign budding yeast Saccharomyces cerevisiae and the benign fission yeast Schizosaccharomyces pombe. We compare their enzymatic and non-enzymatic NO and RNI detoxification mechanisms and summarize fungal responses to nitrosative stress.

scholarly journals Candida glabrata: A Lot More Than Meets the Eye

2019 ◽  
Vol 7 (2) ◽  
pp. 39 ◽  
Author(s):  
Kundan Kumar ◽  
Fizza Askari ◽  
Mahima Sahu ◽  
Rupinder Kaur
Keyword(s):  
Fungal Pathogen ◽  
Biofilm Formation ◽  
Candida Glabrata ◽  
External Environment ◽  
Bloodstream Infections ◽  
Yeast Saccharomyces Cerevisiae ◽  
Pathogenic Yeast ◽  
Human Fungal Pathogen ◽  
Life Threatening ◽  
Inflammatory Immune Response

Candida glabrata is an opportunistic human fungal pathogen that causes superficial mucosal and life-threatening bloodstream infections in individuals with a compromised immune system. Evolutionarily, it is closer to the non-pathogenic yeast Saccharomyces cerevisiae than to the most prevalent Candida bloodstream pathogen, C. albicans. C. glabrata is a haploid budding yeast that predominantly reproduces clonally. In this review, we summarize interactions of C. glabrata with the host immune, epithelial and endothelial cells, and the ingenious strategies it deploys to acquire iron and phosphate from the external environment. We outline various attributes including cell surface-associated adhesins and aspartyl proteases, biofilm formation and stress response mechanisms, that contribute to the virulence of C. glabrata. We further discuss how, C. glabrata, despite lacking morphological switching and secreted proteolytic activity, is able to disarm macrophage, dampen the host inflammatory immune response and replicate intracellularly.

scholarly journals Transcriptional Response ofCandida albicansto Nitric Oxide and the Role of theYHB1Gene in Nitrosative Stress and Virulence

2005 ◽  
Vol 16 (10) ◽  
pp. 4814-4826 ◽  
Author(s):  
Bethann S. Hromatka ◽  
Suzanne M. Noble ◽  
Alexander D. Johnson
Keyword(s):  
Nitric Oxide ◽  
Nitrosative Stress ◽  
Transcriptional Response ◽  
Innate Immune ◽  
No Production ◽  
Human Fungal Pathogen ◽  
Genome Wide ◽  
Prime Determinant

Here, we investigate how Candida albicans, the most prevalent human fungal pathogen, protects itself from nitric oxide (.NO), an antimicrobial compound produced by the innate immune system. We show that exposure of C. albicans to.NO elicits a reproducible and specific transcriptional response as determined by genome-wide microarray analysis. Many genes are transiently induced or repressed by.NO, whereas a set of nine genes remain at elevated levels during.NO exposure. The most highly induced gene in this latter category is YHB1, a flavohemoglobin that detoxifies.NO in C. albicans and other microbes. We show that C. albicans strains deleted for YHB1 have two phenotypes in vitro; they are hypersensitive to.NO and they are hyperfilamentous. In a mouse model of disseminated candidiasis, a YHB1 deleted C. albicans strain shows moderately attenuated virulence, but the virulence defect is not suppressed by deletion of the host NOS2 gene. These results suggest that.NO production is not a prime determinant of virulence in the mouse tail vein model of candidiasis and that the attenuated virulence of a yhb1Δ/yhb1Δ strain is attributable to a defect other than its reduced ability to detoxify.NO.

scholarly journals Detection of gp91-phox precursor protein in B-cell lines from patients with X-linked chronic granulomatous disease as an indicator for mutations impairing cytochrome b558 biosynthesis

1996 ◽  
Vol 315 (2) ◽  
pp. 571-575 ◽  
Author(s):  
Colin D. PORTER ◽  
KURIBAYASHI KURIBAYASHI ◽  
Mohamed H. PARKAR ◽  
Dirk ROOS ◽  
Christine KINNON
Keyword(s):  
Nadph Oxidase ◽  
B Cell ◽  
Chronic Granulomatous Disease ◽  
Cell Lines ◽  
Binding Domain ◽  
Granulomatous Disease ◽  
Cytochrome B558 ◽  
Stable Association ◽  
P22 Phox ◽  
Fad Binding

NADPH oxidase cytochrome b558 consists of two subunits, gp91-phox and p22-phox, defects of which result in chronic granulomatous disease (CGD). The nature of the interaction between these subunits has yet to be determined. Absence of p22-phox in autosomal CGD patient-derived B-cell lines results in detectable levels of an incompletely glycosylated gp91-phox precursor. We have detected this same precursor species in four cell lines from patients with the X-linked form of the disease due to mutations in gp91-phox. Such mutations should delineate regions of gp91-phox important for its biosynthesis, including stable association with p22-phox. One mutation mapped to the putative FAD-binding domain, one mapped to a potential haem-binding domain, and two involved the region encoded by exon 3.

Renal and cardiac oxidative/nitrosative stress in salt-loaded pregnant rat

2007 ◽  
Vol 293 (4) ◽  
pp. R1657-R1665 ◽  
Author(s):  
Annie Beauséjour ◽  
Véronique Houde ◽  
Karine Bibeau ◽  
Rébecca Gaudet ◽  
Jean St-Louis ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Nitrosative Stress ◽  
Gestational Hypertension ◽  
Sodium Intake ◽  
Pregnant Rats ◽  
High Sodium ◽  
High Sodium Intake ◽  
Arterial Blood ◽  
Cardiac Ventricle

Sodium supplementation given for 1 wk to nonpregnant rats induces changes that are adequate to maintain renal and circulatory homeostasis as well as arterial blood pressure. However, in pregnant rats, proteinuria, fetal growth restriction, and placental oxidative stress are observed. Moreover, the decrease in blood pressure and expansion of circulatory volume, normally associated with pregnancy, are prevented by high-sodium intake. We hypothesized that, in these pregnant rats, a loss of the balance between prooxidation and antioxidation, particularly in kidneys and heart, disturbs the normal course of pregnancy and leads to manifestations such as gestational hypertension. We thus investigated the presence of oxidative/nitrosative stress in heart and kidneys following high-sodium intake in pregnant rats. Markers of this stress [8-isoprostaglandin F2α (8-iso-PGF2α) and nitrotyrosine], producer of nitric oxide [nitric oxide synthases (NOSs)], and antioxidants [superoxide dismutase (SOD) and catalase] were measured. Then, molecules (Na+-K+-ATPase and aconitase) or process [apoptosis (Bax and Bcl-2), inflammation (monocyte chemoattractant protein-1, connective tissue growth factor, and TNF-α)] susceptible to free radicals was determined. In kidneys from pregnant rats on 1.8% NaCl-water, NOSs, apoptotic index, and nitrotyrosine expression were increased, whereas Na+-K+-ATPase mRNA and activity were decreased. In the left cardiac ventricle of these rats, heightened nitrotyrosine, 8-iso-PGF2α, and catalase activity together with reduced endothelial NOS protein expression and SOD and aconitase activities were observed. These findings suggest that oxidative/nitrosative stress in kidney and left cardiac ventricle destabilizes the normal course of pregnancy and could lead to gestational hypertension.

scholarly journals Cooperative Roles of Nitric Oxide-Metabolizing Enzymes To Counteract Nitrosative Stress in Enterohemorrhagic Escherichia coli

2019 ◽  
Vol 87 (9) ◽  
Author(s):  
Takeshi Shimizu ◽  
Akio Matsumoto ◽  
Masatoshi Noda
Keyword(s):  
Nitric Oxide ◽  
Escherichia Coli ◽  
Stationary Phase ◽  
Nitrosative Stress ◽  
Enterohemorrhagic Escherichia Coli ◽  
The Other ◽  
Anaerobic Growth ◽  
Bacterial Cells ◽  
Metabolizing Enzymes ◽  
Microaerobic Conditions

ABSTRACT Enterohemorrhagic Escherichia coli (EHEC) has at least three enzymes, NorV, Hmp, and Hcp, that act independently to lower the toxicity of nitric oxide (NO), a potent antimicrobial molecule. This study aimed to reveal the cooperative roles of these defensive enzymes in EHEC against nitrosative stress. Under anaerobic conditions, combined deletion of all three enzymes significantly increased the NO sensitivity of EHEC determined by the growth at late stationary phase; however, the expression of norV restored the NO resistance of EHEC. On the other hand, the growth of Δhmp mutant EHEC was inhibited after early stationary phase, indicating that NorV and Hmp play a cooperative role in anaerobic growth. Under microaerobic conditions, the growth of Δhmp mutant EHEC was inhibited by NO, indicating that Hmp is the enzyme that protects cells from NO stress under microaerobic conditions. When EHEC cells were exposed to a lower concentration of NO, the NO level in bacterial cells of Δhcp mutant EHEC was higher than those of the other EHEC mutants, suggesting that Hcp is effective at regulating NO levels only at a low concentration. These findings of a low level of NO in bacterial cells with hcp indicate that the NO consumption activity of Hcp was suppressed by Hmp at a low range of NO concentrations. Taken together, these results show that the cooperative effects of NO-metabolizing enzymes are regulated by the range of NO concentrations to which the EHEC cells are exposed.

scholarly journals The yjeB (nsrR) Gene of Escherichia coli Encodes a Nitric Oxide-Sensitive Transcriptional Regulator

2006 ◽  
Vol 188 (3) ◽  
pp. 874-881 ◽  
Author(s):  
Diane M. Bodenmiller ◽  
Stephen Spiro
Keyword(s):  
Nitric Oxide ◽  
Escherichia Coli ◽  
Inverted Repeat ◽  
Nitrosative Stress ◽  
Protein A ◽  
Repeat Sequence ◽  
Negative Regulator ◽  
Inverted Repeat Sequence ◽  
Multiple Copies ◽  
Regulatory Model

ABSTRACT Microarray studies of the Escherichia coli response to nitric oxide and nitrosative stress have suggested that additional transcriptional regulators of this response remain to be characterized. We identify here the product of the yjeB gene as a negative regulator of the transcription of the ytfE, hmpA and ygbA genes, all of which are known to be upregulated by nitrosative stress. Transcriptional fusions to the promoters of these genes were expressed constitutively in a yjeB mutant, indicating that all three are targets for repression by YjeB. An inverted repeat sequence that overlaps the −10 element of all three promoters is proposed to be a binding site for the YjeB protein. A similar inverted repeat sequence was identified in the tehA promoter, which is also known to be sensitive to nitrosative stress. The ytfE, hmpA, ygbA, and tehA promoters all caused derepression of a ytfE-lacZ transcriptional fusion when present in the cell in multiple copies, presumably by a repressor titration effect, suggesting the presence of functional YjeB binding sites in these promoters. However, YjeB regulation of tehA was weak, as judged by the activity of a tehA-lacZ fusion, perhaps because YjeB repression of tehA is masked by other regulatory mechanisms. Promoters regulated by YjeB could be derepressed by iron limitation, which is consistent with an iron requirement for YjeB activity. The YjeB protein is a member of the Rrf2 family of transcriptional repressors and shares three conserved cysteine residues with its closest relatives. We propose a regulatory model in which the YjeB repressor is directly sensitive to nitrosative stress. On the basis of similarity to the nitrite-responsive repressor NsrR from Nitrosomonas europaea, we propose that the yjeB gene of E. coli be renamed nsrR.

Abstract 484: Nitrosative Stress Enhances S-nitrosation Of Peroxiredoxins In The Heart

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Michael Reinartz ◽  
Zhaoping Ding ◽  
Axel Gödecke ◽  
Jürgen Schrader
Keyword(s):  
Nitric Oxide ◽  
Nitrosative Stress ◽  
Protein S ◽  
List Type ◽  
Basal Expression ◽  
Protein Thiols ◽  
Wide Range ◽  
Well Data ◽  
Oxide Synthase ◽  
Biotin Switch

Nitric oxide (NO) is produced by different isoforms of NO-synthases and operates as a mediator of important cell signaling pathways. To explore thiol-based protein modifications in a situation of nitrosative stress, two transgenic mouse models recently generated in our laboratory were used: Cardiac specific overexpression of inducible nitric oxide synthase (iNOS) (tg-iNOS + ) and tg-iNOS + with concomitant myoglobin-deficiency (tg-iNOS + /myo −/− ). Protein S-nitrosation, an important redox-based posttranslational modification, revealed no differences between WT and tg-iNOS + hearts as measured by the biotin-switch assay and 2-D PAGE. Even in the absence of myoglobin - an efficient endogenous NO-oxidase - the protein S-nitrosation pattern for nearly all the detected proteins (>40) remained unchanged in the tg-iNOS + /myo −/− hearts, with the exception of three proteins. Tandem mass spectrometry uncovered these proteins as peroxiredoxins (Prx II, III, VI), which are known to possess peroxidase activity, whereby hydrogen peroxide, peroxynitrite and a wide range of organic hydroperoxides are reduced and detoxified. To prove whether the higher abundance of the Prxs was due to enhanced S-nitrosation or due to changes in their basal expression levels, immunoblotting with specific antibodies was applied and revealed upregulation of Prx VI in tg-iNOS + /myo −/− hearts. The other proteins found to be S-nitrosated were identified as well. Data mining indicated a significant overlap of these proteins with proteins becoming glutathiolated. Protein glutathiolation detected by immunoblotting was enhanced in the tg-iNOS + hearts and even more so in the tg-iNOS + /myo −/− hearts. We conclude that protein glutathiolation in our transgenic model of nitrosative stress is important to protect protein thiols from irreversible oxidation. The upregulation of antioxidant proteins like Prx VI appears to be an additional mechanism to antagonize an excess of reactive oxygen/nitrogen species. Enhanced S-nitrosation of the Prxs may serve a new function in the signalling cascade coping with nitrosative stress.

The content of nitric oxide and S-nitrosothiols in rats’ liver cells under the different supplementation of macronutrient

2020 ◽  
Vol 12 (2) ◽  
pp. 187-195
Author(s):  
Halyna Kopylchuk ◽  
Ivanna Nykolaichuk ◽  
Olesiia Kuziak
Keyword(s):  
Nitric Oxide ◽  
Nitrogen Oxide ◽  
Nitrosative Stress ◽  
Liver Cells ◽  
Oxide Content ◽  
Experimental Conditions ◽  
Before And After ◽  
Rat Liver Cells ◽  
Key Factor ◽  
Excessive Consumption

This paper presents studies of nitric oxide and low-molecular S-nitrosothiols in the mitochondrial and cytosolic fractions of the rats' liver under the conditions of, alimentary protein deprivation, consumption of excess sucrose content and combined action of two adverse factors. In order to model the low-protein diet of the animal for 28 days received an isocaloric diet containing 4.7% protein, 10% fat, 81,3% carbohydrates (starch – 37%, sucrose – 30%, cellulose – 5%) and was calculated in accordance with the recommendations of the American Institute of Nutrition. The high-sugar diet consisted of 14% protein, 10% fat, 72% carbohydrates (starch – 37%, sucrose – 30%, cellulose – 5%). The mitochondrial and cytosolic fraction of rat liver cells were obtained by the method of differential centrifugation. Nitrogen oxide content was assessed by a unified method by determining the NO2- content, which is a stable metabolite of nitric oxide. Since NO is inactivated into an oxidase reaction with the conversion into nitrite or nitrate that is quickly metabolized, the nitrogen oxide content was assessed by the change in NO2-. The concentration of S-nitrosothiols was recorded, respectively, by determining the concentration of nitrite anion before and after the addition of Hg2+ ions, which by modifying the S – N bonds catalyzes the release of S-nitrosyl thiols of nitric oxide. An increase in NO content in both hepatic subcellular fractions of the rats’ experimental groups compared to control values was found. However, a lack of protein in the diet (protein deficiency in the diet leads to an increase in nitric oxide levels in 3-4 times) can be considered as a key factor in the recorded changes in the mitochondria of the animals’ liver, while in the cytosol - excessive consumption of sucrose (3-5 times increase). Regarding the level of S-nitrosothiols, in the studied fractions, multidirectional changes in their concentration were found. Thus, an increase in the content of nitrosyl derivatives in the mitochondria of rat’s liver cells with a simultaneous decrease in their level in the cytosol indicates dysmetabolic disorders in the transport system and deposition of nitric oxide, which can lead to the development of nitrosative stress under the experimental conditions.

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