scholarly journals Atg32 dependent mitophagy sustains spermidine and nitric oxide required for heat stress tolerance in S. cerevisiae

2021 ◽  
Author(s):  
Jasvinder Kaur ◽  
Juliet Goldsmith ◽  
Alexandra Tankka ◽  
Sofía Bustamante Eguiguren ◽  
Alfredo A. Gimenez ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heat Stress ◽  
Molecular Mechanisms ◽  
Physiological Role ◽  
No Production ◽  
Polyamine Biosynthesis ◽  
Adenosyl Methionine ◽  
Autophagic Degradation ◽  
Respiratory Growth ◽  
Induced Defects

In Saccharomyces cerevisiae, the selective autophagic degradation of mitochondria, termed mitophagy, is critically regulated by the adapter protein, Atg32. Despite our knowledge about the molecular mechanisms by which Atg32 controls mitophagy, its physiological roles in yeast survival and fitness remains less clear. Here, we demonstrate a requirement for Atg32 in promoting spermidine production during respiratory growth and heat-induced mitochondrial stress. During respiratory growth, mitophagy-deficient yeast exhibit profound heat-stress induced defects in growth and viability due to impaired biosynthesis of spermidine and its biosynthetic precursor S-Adenosyl-Methionine (SAM). Moreover, spermidine production is crucial for the induction of cytoprotective nitric oxide (NO) during heat stress. Hence, the re-addition of spermidine to Atg32 mutant yeast is sufficient to both enhance NO production and restore respiratory growth during heat stress. Our findings uncover a previously unrecognized physiological role for yeast mitophagy in spermidine metabolism and illuminate new interconnections between mitophagy, polyamine biosynthesis and NO signaling.

The Signaling Pathways in Nitric Oxide Production by Neutrophils Exposed to N-nitrosodimethylamine

2018 ◽  
Vol 16 (2) ◽  
pp. 194-199
Author(s):  
Wioletta Ratajczak-Wrona ◽  
Ewa Jablonska
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Polymorphonuclear Neutrophils ◽  
Microbial Pathogens ◽  
Human Neutrophils ◽  
No Production ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Background: Polymorphonuclear neutrophils (PMNs) play a crucial role in the innate immune system’s response to microbial pathogens through the release of reactive nitrogen species, including Nitric Oxide (NO). </P><P> Methods: In neutrophils, NO is produced by the inducible Nitric Oxide Synthase (iNOS), which is regulated by various signaling pathways and transcription factors. N-nitrosodimethylamine (NDMA), a potential human carcinogen, affects immune cells. NDMA plays a major part in the growing incidence of cancers. Thanks to the increasing knowledge on the toxicological role of NDMA, the environmental factors that condition the exposure to this compound, especially its precursors- nitrates arouse wide concern. Results: In this article, we present a detailed summary of the molecular mechanisms of NDMA’s effect on the iNOS-dependent NO production in human neutrophils. Conclusion: This research contributes to a more complete understanding of the mechanisms that explain the changes that occur during nonspecific cellular responses to NDMA toxicity.

scholarly journals Identification of Potential Calorie Restriction-Mimicking Yeast Mutants with Increased Mitochondrial Respiratory Chain and Nitric Oxide Levels

2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Bin Li ◽  
Craig Skinner ◽  
Pablo R. Castello ◽  
Michiko Kato ◽  
Erin Easlon ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Calorie Restriction ◽  
Mitochondrial Respiration ◽  
Molecular Mechanisms ◽  
Mitochondrial Respiratory Chain ◽  
Yeast Cells ◽  
Mitochondrial Activity ◽  
No Production ◽  
Hypoxic Conditions ◽  
Yeast Mutants

Calorie restriction (CR) induces a metabolic shift towards mitochondrial respiration; however, molecular mechanisms underlying CR remain unclear. Recent studies suggest that CR-induced mitochondrial activity is associated with nitric oxide (NO) production. To understand the role of mitochondria in CR, we identify and studySaccharomyces cerevisiaemutants with increased NO levels as potential CR mimics. Analysis of the top 17 mutants demonstrates a correlation between increased NO, mitochondrial respiration, and longevity. Interestingly, treating yeast with NO donors such as GSNO (S-nitrosoglutathione) is sufficient to partially mimic CR to extend lifespan. CR-increased NO is largely dependent on mitochondrial electron transport and cytochrome c oxidase (COX). Although COX normally produces NO under hypoxic conditions, CR-treated yeast cells are able to produce NO under normoxic conditions. Our results suggest that CR may derepress some hypoxic genes for mitochondrial proteins that function to promote the production of NO and the extension of lifespan.

scholarly journals Prolactin activation of mammary nitric oxide synthase: molecular mechanisms

2002 ◽  
Vol 28 (1) ◽  
pp. 45-51 ◽  
Author(s):  
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase ◽  
Intracellular Calcium ◽  
Molecular Mechanisms ◽  
Mammary Epithelial Cells ◽  
Calcium Ionophore ◽  
Mammary Epithelial ◽  
No Production ◽  
2B Protein ◽  
Oxide Synthase

Prolactin (PRL) is capable of stimulating both calcium and nitric oxide (NO) accumulation in mammary epithelial cells within 15min. A calcium ionophore was also able to stimulate NO levels to an extent similar to that generated by PRL. Furthermore, maximal concentrations of PRL and the ionophore were not additive, suggesting that they were both using the same pathway, i.e. calcium. Finally, the depletion of intracellular calcium completely abrogated the effect of PRL on NO production. No other pathway known to affect NO synthase (NOS) influenced the action of PRL. Specifically, manipulations of protein phosphatase 2B, protein kinase B (PKB), protein kinase C (PKC), and arginine transport did not alter the activation of NOS by PRL. Therefore, the ability of PRL to stimulate NO production at 15min can be completely explained by its ability to elevate intracellular calcium.

scholarly journals Nitric Oxide Synthase inhibition counteracts the stress-induced DNA methyltransferase 3b expression in the hippocampus of rats

2020 ◽  
Author(s):  
Izaque de Sousa Maciel ◽  
Amanda Juliana Sales ◽  
Plinio C Casarotto ◽  
Eero Castrén ◽  
Caroline Biojone ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mrna Expression ◽  
Learned Helplessness ◽  
Hippocampal Neurons ◽  
Dna Methyltransferase ◽  
Molecular Mechanisms ◽  
Calcium Influx ◽  
No Production ◽  
Dna Methyltransferase 3B ◽  
Nos Inhibitors

AbstractIt has been postulated that activation of NMDA receptors (NMDAr) and nitric oxide (NO) production in the hippocampus is involved in the behavioral consequences of stress. Stress triggers NMDAr-induced calcium influx in limbic areas, such as the hippocampus, which in turn activates neuronal NO synthase (nNOS). Inhibition of nNOS or NMDAr activity can prevent stress-induced effects in animal models, but the molecular mechanisms behind this effect are still unclear. In this study, cultured hippocampal neurons treated with NMDA or dexamethasone showed increased of DNA methyltransferase 3b (DNMT3b) mRNA expression, which was blocked by pre-treatment with nNOS inhibitor nω-propyl-L-arginine (NPA). In rats submitted to the Learned Helplessness paradigm (LH), we observed that inescapable stress increased of DNMT3b mRNA expression at 1h and 24h in the hippocampus. The NOS inhibitors 7-NI and aminoguanidine (AMG) decreased the number of escape failures in LH, and counteracted the changes in hippocampal DNMT3b mRNA induced in this behavioral paradigm. Altogether, our data suggest that NO produced in response to NMDAr activation following stress upregulates DNMT3b in the hippocampus.

scholarly journals Physiology of Nitric Oxide in the Respiratory System

2017 ◽  
pp. S159-S172 ◽  
Author(s):  
M. ANTOSOVA ◽  
D. MOKRA ◽  
L. PEPUCHA ◽  
J. PLEVKOVA ◽  
T. BUDAY ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Lung Development ◽  
Clinical Manifestations ◽  
Physiological Role ◽  
No Production ◽  
Physiological Processes ◽  
Frequent Use ◽  
Organ Systems ◽  
Surfactant Production ◽  
And Function

Nitric oxide (NO) is an important endogenous neurotransmitter and mediator. It participates in regulation of physiological processes in different organ systems including airways. Therefore, it is important to clarify its role in the regulation of both airway and vascular smooth muscle, neurotransmission and neurotoxicity, mucus transport, lung development and in the surfactant production. The bioactivity of NO is highly variable and depends on many factors: the presence and activity of NO-producing enzymes, activity of competitive enzymes (e.g. arginase), the amount of substrate for the NO production, the presence of reactive oxygen species and others. All of these can change NO primary physiological role into potentially harmful. The borderline between them is very fragile and in many cases not entirely clear. For this reason, the research focuses on a comprehensive understanding of NO synthesis and its metabolic pathways, genetic polymorphisms of NO synthesizing enzymes and related effects. Research is also motivated by frequent use of exhaled NO monitoring in the clinical manifestations of respiratory diseases. The review focuses on the latest knowledge about the production and function of this mediator and understanding the basic physiological processes in the airways.

scholarly journals Phosphorylation inactivation of endothelial nitric oxide synthesis in pulmonary arterial hypertension

2016 ◽  
Vol 310 (11) ◽  
pp. L1199-L1205 ◽  
Author(s):  
Sudakshina Ghosh ◽  
Manveen Gupta ◽  
Weiling Xu ◽  
Deloris A. Mavrakis ◽  
Allison J. Janocha ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Molecular Mechanisms ◽  
Vascular Endothelial Cells ◽  
Vascular Diseases ◽  
No Production ◽  
Pulmonary Arterial

The impairment of vasodilator nitric oxide (NO) production is well accepted as a typical marker of endothelial dysfunction in vascular diseases, including in the pathophysiology of pulmonary arterial hypertension (PAH), but the molecular mechanisms accounting for loss of NO production are unknown. We hypothesized that low NO production by pulmonary arterial endothelial cells in PAH is due to inactivation of NO synthase (eNOS) by aberrant phosphorylation of the protein. To test the hypothesis, we evaluated eNOS levels, dimerization, and phosphorylation in the vascular endothelial cells and lungs of patients with PAH compared with controls. In mechanistic studies, eNOS activity in endothelial cells in PAH lungs was found to be inhibited due to phosphorylation at T495. Evidence pointed to greater phosphorylation/activation of protein kinase C (PKC) α and its greater association with eNOS as the source of greater phosphorylation at T495. The presence of greater amounts of pT495-eNOS in plexiform lesions in lungs of patients with PAH confirmed the pathobiological mechanism in vivo. Transfection of the activating mutation of eNOS (T495A/S1177D) restored NO production in PAH cells. Pharmacological blockade of PKC activity by β-blocker also restored NO formation by PAH cells, identifying one mechanism by which β-blockers may benefit PAH and cardiovascular diseases through recovery of endothelial functions.

scholarly journals Nitric Oxide: From Gastric Motility to Gastric Dysmotility

2021 ◽  
Vol 22 (18) ◽  
pp. 9990
Author(s):  
Eglantina Idrizaj ◽  
Chiara Traini ◽  
Maria Giuliana Vannucchi ◽  
Maria Caterina Baccari
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Gastric Motility ◽  
Muscle Relaxation ◽  
Physiological Role ◽  
Smooth Muscle Relaxation ◽  
No Production ◽  
Main Role ◽  
Motor Responses

It is known that nitric oxide (NO) plays a key physiological role in the control of gastrointestinal (GI) motor phenomena. In this respect, NO is considered as the main non-adrenergic, non-cholinergic (NANC) inhibitory neurotransmitter responsible for smooth muscle relaxation. Moreover, many substances (including hormones) have been reported to modulate NO production leading to changes in motor responses, further underlying the importance of this molecule in the control of GI motility. An impaired NO production/release has indeed been reported to be implicated in some GI dysmotility. In this article we wanted to focus on the influence of NO on gastric motility by summarizing knowledge regarding its role in both physiological and pathological conditions. The main role of NO on regulating gastric smooth muscle motor responses, with particular reference to NO synthases expression and signaling pathways, is discussed. A deeper knowledge of nitrergic mechanisms is important for a better understanding of their involvement in gastric pathophysiological conditions of hypo- or hyper-motility states and for future therapeutic approaches. A possible role of substances which, by interfering with NO production, could prove useful in managing such motor disorders has been advanced.

scholarly journals L-Citrulline Influences the Body Temperature, Heat Shock Response and Nitric Oxide Regeneration of Broilers Under Thermoneutral and Heat Stress Condition

2021 ◽  
Vol 12 ◽  
Author(s):  
Victoria A. Uyanga ◽  
Minghui Wang ◽  
Tian Tong ◽  
Jingpeng Zhao ◽  
Xiaojuan Wang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heat Stress ◽  
Heat Shock ◽  
Body Temperature ◽  
Mrna Expression ◽  
Heat Shock Response ◽  
Control Diet ◽  
The Body ◽  
No Production ◽  
Shock Response

Heat stress (HS) adversely affects several physiological responses in organisms, but the underlying molecular mechanisms involved are yet to be fully understood. L-Citrulline (L-Cit) is a nutraceutical amino acid that is gaining research interest for its role in body temperature regulation and nitric oxide synthesis. This study investigated whether dietary supplementation with L-Cit (1% of basal diet) could ameliorate the effects of acute HS on thermotolerance, redox balance, and inflammatory responses of broilers. Ross 308 broilers (288 chicks) were subjected to two environments; thermoneutral at 24°C (TNZ) or HS at 35°C for 5 h, and fed two diets; control or L-Cit. The results showed that HS increased the ear, rectal (RT), and core body (CBT) temperatures of broilers, along with higher respiratory rate. The RT and CBT readings were intermittently affected with time effect, whereas, L-Cit supplementation lowered the mean CBT than the control diet. Antioxidant assays showed that superoxide dismutase was increased during HS, while, catalase was promoted by L-Cit supplementation. In addition, L-Cit induced glutathione peroxidase activity compared to the control diet during HS. Hypothalamic heat shock protein (HSP)-90 was upregulated by HS, but L-Cit downregulated heat shock factor (HSF)-1, and HSP 60 mRNA expressions. HSF 3 mRNA expression was downregulated by L-Cit under TNZ condition. More so, HS increased the plasma nitric oxide (NO) concentration but lowered the total NO synthase (tNOS) activity. In contrast, L-Cit supplementation limited NO production but increased the tNOS activity. Arginase activity was increased in the control fed group during HS but L-Cit supplementation lowered this effect. The NOS-COX pathway was significantly affected under TNZ condition, since L-Cit supplementation downregulated the mRNA expression of iNOS-COX2 in the hypothalamus, and further reduced the serum PGE2 concentration. Together, these data indicates that L-Cit influenced the antioxidant defense, heat shock response and nitric oxide regeneration both under thermoneutral and HS conditions; and that L-Cit may be directly and/or indirectly involved in the central regulation of body temperature.

scholarly journals Subcellular targeting and trafficking of nitric oxide synthases

2006 ◽  
Vol 396 (3) ◽  
pp. 401-409 ◽  
Author(s):  
Stefanie Oess ◽  
Ann Icking ◽  
David Fulton ◽  
Roland Govers ◽  
Werner Müller-Esterl
Keyword(s):  
Nitric Oxide ◽  
Molecular Mechanisms ◽  
No Production ◽  
Subcellular Targeting ◽  
Post Translational Modifications ◽  
Intracellular Targeting ◽  
Highly Active ◽  
Signalling Molecule ◽  
Close Proximity ◽  
And Function

Unlike most other endogenous messengers that are deposited in vesicles, processed on demand and/or secreted in a regulated fashion, NO (nitric oxide) is a highly active molecule that readily diffuses through cell membranes and thus cannot be stored inside the producing cell. Rather, its signalling capacity must be controlled at the levels of biosynthesis and local availability. The importance of temporal and spatial control of NO production is highlighted by the finding that differential localization of NO synthases in cardiomyocytes translates into distinct effects of NO in the heart. Thus NO synthases belong to the most tightly controlled enzymes, being regulated at transcriptional and translational levels, through co- and post-translational modifications, by substrate availability and not least via specific sorting to subcellular compartments, where they are in close proximity to their target proteins. Considerable efforts have been made to elucidate the molecular mechanisms that underlie the intracellular targeting and trafficking of NO synthases, to ultimately understand the cellular pathways controlling the formation and function of this powerful signalling molecule. In the present review, we discuss the mechanisms and triggers for subcellular routing and dynamic redistribution of NO synthases and the ensuing consequences for NO production and action.

scholarly journals Estrogen Modulates Microglial Inflammatory Mediator Production via Interactions with Estrogen Receptor β

Endocrinology ◽  
2004 ◽  
Vol 145 (11) ◽  
pp. 5021-5032 ◽  
Author(s):  
Ann E. Baker ◽  
Vielska M. Brautigam ◽  
Jyoti J. Watters
Keyword(s):  
Nitric Oxide ◽  
Molecular Mechanisms ◽  
Mapk Pathway ◽  
Cyclooxygenase 2 ◽  
No Production ◽  
Transcriptional Responses ◽  
Neuroprotective Effects ◽  
Pathway Activation ◽  
Microglial Cell Line ◽  
Antiinflammatory Effects

Abstract Estrogens are well known to exert antiinflammatory effects outside the central nervous system (CNS). They have also been shown to exert neuroprotective effects in the CNS after several types of injury, including neurodegeneration. However, the molecular mechanisms by which these effects occur remain unclear. Because microglial hyperactivation and their production of neurotoxins is associated with many types of brain injury for which estrogens are beneficial, we sought to investigate the ability of estrogen to modulate microglial function. Furthermore, because little is known regarding the role of each of the two known estrogen receptors (ERs) in microglia, our studies were designed to test the hypothesis that 17β-estradiol (E2) exerts antiinflammatory effects in microglia, specifically via interactions with ERβ. We tested this hypothesis using the murine microglial cell line BV-2, which naturally expresses only ERβ. Our results indicate that not only does E2 decrease lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression, it also reduces the expression of cyclooxygenase-2, a target for estrogen that has not previously been reported for ERβ. We also observed that LPS-stimulated TNFα mRNA was increased by estrogen. E2 exerts these effects within 30 min compared with typical estrogen transcriptional responses. Tamoxifen and ICI 182,780 differentially blocked the inhibitory effects of E2 on LPS-stimulated iNOS and cyclooxygenase-2. In addition, we show that E2 alters LPS-stimulated MAPK pathway activation, supporting the idea that alterations in the MAPKs may be a potential mechanism by which ERβ mediates decreased microglial activation.

Sign in / Sign up

Export Citation Format

Share Document