scholarly journals Increased iNOS and Nitrosative Stress in Dopaminergic Neurons of MDMA-Exposed Rats

2019 ◽  
Vol 20 (5) ◽  
pp. 1242 ◽  
Author(s):  
Stefania Schiavone ◽  
Margherita Neri ◽  
Angela Maffione ◽  
Paolo Frisoni ◽  
Maria Morgese ◽  
...  

Several mechanisms underlying 3,4-Methylenedioxy-N-methylamphetamine (MDMA) neurotoxicity have been proposed, including neurochemical alterations and excitotoxicity mediated by reactive oxygen species (ROS), nitric oxide (NO), and reactive nitrogen species (RNS). However, ROS, NO, and RNS sources in the brain are not fully known. We aimed to investigate possible alterations in the expression of the ROS producer NOX enzymes (NOX2, NOX1, and NOX4), NO generators (iNOS, eNOS, and nNOS), markers of oxidative (8-hydroxy-2′-deoxyguanosine, 8OHdG), and nitrosative (3-nitrotyrosine, NT) stress, as well as the colocalization between cells positive for the dopamine transporter (DT1) and cells expressing the neuronal nuclei (NeuN) marker, in the frontal cortex of rats receiving saline or MDMA, sacrificed 6 h, 16 h, or 24 h after its administration. MDMA did not affect NOX2, NOX1, and NOX4 immunoreactivity, whereas iNOS expression was enhanced. The number of NT-positive cells was increased in MDMA-exposed animals, whereas no differences were detected in 8OHdG expression among experimental groups. MDMA and NT markers colocalized with DT1 positive cells. DT1 immunostaining was found in NeuN-positive stained cells. Virtually no colocalization was observed with microglia and astrocytes. Moreover, MDMA immunostaining was not found in NOX2-positive cells. Our results suggest that iNOS-derived nitrosative stress, but not NOX enzymes, may have a crucial role in the pathogenesis of MDMA-induced neurotoxicity, highlighting the specificity of different enzymatic systems in the development of neuropathological alterations induced by the abuse of this psychoactive compound.

Nanoscale ◽  
2021 ◽  
Author(s):  
Rachael Knoblauch ◽  
Chris Geddes

While the utility of reactive oxygen species in photodynamic therapies for both cancer treatments and antimicrobial applications has received much attention, the inherent potential of reactive nitrogen species (RNS) including...


2005 ◽  
Vol 16 (10) ◽  
pp. 4792-4813 ◽  
Author(s):  
M. Paige Nittler ◽  
Davina Hocking-Murray ◽  
Catherine K. Foo ◽  
Anita Sil

The pathogenic fungus Histoplasma capsulatum escapes innate immune defenses and colonizes host macrophages during infection. After the onset of adaptive immunity, the production of the antimicrobial effector nitric oxide (.NO) restricts H. capsulatum replication. However, H. capsulatum can establish persistent infections, indicating that it survives in the host despite exposure to reactive nitrogen species (RNS). To understand how H. capsulatum responds to RNS, we determined the transcriptional profile of H. capsulatum to.NO-generating compounds using a shotgun genomic microarray. We identified 695 microarray clones that were induced ≥4-fold upon nitrosative stress. Because our microarray clones were generated from random fragments of genomic DNA, they did not necessarily correspond to H. capsulatum open reading frames. To identify induced genes, we used high-density oligonucleotide tiling arrays to determine the genomic boundaries and coding strand of 153 RNS-induced transcripts. Homologues of these genes in other organisms are involved in iron acquisition, energy production, stress response, protein folding/degradation, DNA repair, and.NO detoxification. Ectopic expression of one of these genes, a P450 nitric oxide reductase homologue, was sufficient to increase resistance of H. capsulatum to RNS in culture. We propose that H. capsulatum uses the pathways identified here to cope with RNS-induced damage during pathogenesis.


2005 ◽  
Vol 27 (3) ◽  
pp. 9-14
Author(s):  
Aimee L. Landar ◽  
Jaroslaw W. Zmijewski ◽  
Joo-Yeun Oh ◽  
Victor M. Darley-Usmar

Some of the earliest studies in bioenergetics described a ‘leak’ of electrons from the mitochondrial respiratory chain to oxygen, with the resulting formation of the simple one-electron product, superoxide. Several lines of evidence led to the idea that this process is pathological. For example, formation of superoxide, and its dismutation product hydrogen peroxide, from the mitochondrion was enhanced by mitochondrial poisons and hyperoxia. Since these early beginnings, studies in the redox cell signalling field have shown that these same reactive oxygen species (ROS) and reactive nitrogen species (RNS), such as nitric oxide (NO), serve as signalling molecules in both physiological and pathological situations. These small molecules can act through several mechanisms, including the ability to act as reversible agonists for receptors.


2006 ◽  
Vol 34 (5) ◽  
pp. 953-956 ◽  
Author(s):  
G.C. Brown ◽  
V. Borutaite

ROS (reactive oxygen species) and RNS (reactive nitrogen species) are central to the innate immunity that protects us from infection, but also contribute to degenerative diseases and possibly aging. However, ROS and RNS are increasingly recognized to contribute to physiological signalling. This review briefly describes the main interactions between ROS and RNS and shows how their origins, chemistry, metabolism and biological actions are intimately linked.


2017 ◽  
Vol 398 (11) ◽  
pp. 1193-1208 ◽  
Author(s):  
Sujeenthar Tharmalingam ◽  
Azhar Alhasawi ◽  
Varun P. Appanna ◽  
Joe Lemire ◽  
Vasu D. Appanna

AbstractNitrosative stress results from an increase in reactive nitrogen species (RNS) within the cell. Though the RNS – nitric oxide (·NO) and peroxynitrite (ONOO−) – play pivotal physiological roles, at elevated concentrations, these moieties can be poisonous to both prokaryotic and eukaryotic cells alike due to their capacity to disrupt a variety of essential biological processes. Numerous microbes are known to adapt to nitrosative stress by elaborating intricate strategies aimed at neutralizing RNS. In this review, we will discuss both the enzymatic systems dedicated to the elimination of RNS as well as the metabolic networks that are tailored to generate RNS-detoxifying metabolites – α-keto-acids. The latter has been demonstrated to nullify RNS via non-enzymatic decarboxylation resulting in the production of a carboxylic acid, many of which are potent signaling molecules. Furthermore, as aerobic energy production is severely impeded during nitrosative stress, alternative ATP-generating modules will be explored. To that end, a holistic understanding of the molecular adaptation to nitrosative stress, reinforces the notion that neutralization of toxicants necessitates significant metabolic reconfiguration to facilitate cell survival. As the alarming rise in antimicrobial resistant pathogens continues unabated, this review will also discuss the potential for developing therapies that target the alternative ATP-generating machinery of bacteria.


2021 ◽  
Author(s):  
Cristina Parisi ◽  
Mariacristina Failla ◽  
Aurore Fraix ◽  
Luca Menilli ◽  
Francesca Moret ◽  
...  

The generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) as “unconventional” therapeutics with precise spatiotemporal control by using light stimuli may open entirely new horizons for innovative...


Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 466
Author(s):  
Rachid Skouta

Maintaining the physiological level of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the body is highly important in the fight against radical species in the context of human health [...]


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Micol Falabella ◽  
Elena Forte ◽  
Maria Chiara Magnifico ◽  
Paolo Santini ◽  
Marzia Arese ◽  
...  

Here we have collected evidence suggesting that chronic changes in the NO homeostasis and the rise of reactive oxygen species bioavailability can contribute to cell dysfunction in Leber’s hereditary optic neuropathy (LHON) patients. We report that peripheral blood mononuclear cells (PBMCs), derived from a female LHON patient with bilateral reduced vision and carrying the pathogenic mutation 11778/ND4, display increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS), as revealed by flow cytometry, fluorometric measurements of nitrite/nitrate, and 3-nitrotyrosine immunodetection. Moreover, viability assays with the tetrazolium dye MTT showed that lymphoblasts from the same patient are more sensitive to prolonged NO exposure, leading to cell death. Taken together these findings suggest that oxidative and nitrosative stress cooperatively play an important role in driving LHON pathology when excess NO remains available over time in the cell environment.


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