Relevance of peroxynitrite formation and 3-nitrotyrosine on spermatozoa physiology

Cruz, Daniel Filipe; Fardilha, Margarida

doi:10.1016/j.pbj.2016.07.004

Cited by 19 publications

(17 citation statements)

References 96 publications

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“…Next, we aimed to directly measure peroxynitrite-mediated damage of aconitase. Nitration of tyrosine residues is an established method that can be used as a fingerprint of peroxynitrite-mediated damage of proteins (35, 36). It should be noted that studies using purified mitochondrial aconitase suggest that peroxynitrite-mediated disruption of the [4Fe-4S] 2+ cluster of aconitase is most likely responsible for enzyme inactivation, although nitration of tyrosine residues and oxidation of cysteine residues may contribute to activity loss (33, 37-39).…”

Section: Resultsmentioning

confidence: 99%

Macrophage-produced peroxynitrite induces antibiotic tolerance and supersedes intrinsic mechanisms of persister formation

Beam

Wagner

Shook

et al. 2021

Preprint

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Staphylococcus aureus is a leading human pathogen that frequently causes chronic and relapsing infections. Antibiotic tolerant persister cells contribute to frequent antibiotic failure in patients. Macrophages represent an important niche during S. aureus bacteremia and recent work has identified a role for oxidative burst in the formation of antibiotic tolerant S. aureus. We find that host-derived peroxynitrite, the reaction product of superoxide and nitric oxide, is the main mediator of antibiotic tolerance in macrophages. Using a collection of S. aureus clinical isolates, we find that, despite significant variation in persister formation in pure culture, all strains were similarly enriched for antibiotic tolerance following internalization by activated macrophages. Our findings suggest that host interaction strongly induces antibiotic tolerance and may negate bacterial mechanisms of persister formation, established in pure culture. These findings emphasize the importance of studying antibiotic tolerance in the context of bacterial interaction with the host suggest that modulation of the host response may represent a viable therapeutic strategy to sensitize S. aureus to antibiotics.

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Section: Resultsmentioning

confidence: 99%

Macrophage-produced peroxynitrite induces antibiotic tolerance and supersedes intrinsic mechanisms of persister formation

Beam

Wagner

Shook

et al. 2021

Preprint

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“…The effects of peroxynitrite can be both positive and negative depending on their concentration and environment upon which they are acting. Cruz & Fardilha, (2016) did not observe any correlation between semen parameters and 3-NT. Vignini et al (2006), however, documented a significant correlation between peroxynitrite concentration and semen parameter such as motility.…”

Section: Discussionmentioning

confidence: 53%

“…On the contrary, Cruz & Fardilha (2016)did not find any correlations between 3-NT and semen parameters.…”

Section: Discussionmentioning

confidence: 59%

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Male infertility: Role of vitamin D and oxidative stress markers

et al. 2021

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Spermatozoa are vulnerable to oxidative stress because of their inherent reduced antioxidant defence and DNA repair mechanisms. Polyunsaturated fatty acids in sperm plasma membrane break down to cytotoxic lipid aldehyde, 4‐Hydroxynonenal, whereas 3‐Nitrotyrosine is generated by peroxynitrite induced tyrosine nitration. Both oxidative stress markers contribute to altered sperm function and infertility. Vitamin D, a membrane antioxidant, has a potential scavenger capacity. We compared oxidative stress markers and vitamin D in male subjects with normal and altered sperm parameters and explored association of these markers: 4‐Hydroxynonenal and 3‐Nitrotyrosine with Vitamin D. Higher 4‐Hydroxynonenal levels in altered sperm parameter group and a negative correlation with sperm count, motility and morphology (p < 0.001) was observed. Vitamin D serum concentration in altered sperm parameters was less (p = 0.016) showing a significant positive correlation with sperm count and morphology. 4‐Hydroxynonenal was significantly higher in altered sperm parameters showing negative correlation with vitamin D. Highest serum concentrations of 4‐Hydroxynonenal were observed in vitamin D‐deficient subjects. Significantly higher concentration of 4‐Hydroxynonenal was estimated in altered sperm parameters of vitamin D sufficient group (p < 0.001). This suggests 4‐Hydroxynonenal as an oxidative stress marker leading to altered sperm function and infertility with some association with vitamin D; needs to be explored.

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“…A consequence derived from oxidative stress is that ONOO − rapidly reacts with the sulfhydryl group, as reported in human spermatozoa, where the adverse effect of peroxynitrite in motility is mediated by an increased oxidation in the thiol groups of sperm proteins [10] or by depletion of total sulphydryl group in sperm proteins [21]. In addition, ONOO − can cause tyrosine nitration, mostly in specific functional domains of sperm proteins, promoting structure and conformations changes that may be responsible for the alteration or inactivation of sperm proteins function [13,33]. Although we have not specifically evaluated protein tyrosine nitration or thiol oxidation groups in boar spermatozoa, we demonstrate that lipid peroxidation occurs in response to ONOO − and thus, we propose that those sperm proteins very sensitive to oxidative stress that are involved in molecular mechanisms of sperm motility can likely become oxidized and inactivated by ONOO − , leading to an impairment in boar sperm motility.…”

Section: Discussionmentioning

confidence: 97%

Molecular Mechanisms Involved in the Impairment of Boar Sperm Motility by Peroxynitrite-Induced Nitrosative Stress

Serrano

Garrido

Céspedes

et al. 2020

IJMS

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Excessive levels of reactive nitrogen species (RNS) produce nitrosative stress. Among RNS is peroxynitrite, a highly reactive free radical generated when nitric oxide reacts with superoxide anion. Peroxynitrite effects have been mainly studied in somatic cells, and in spermatozoa the majority of studies are focused in humans. The aim of this study is to investigate the in vitro peroxynitrite effect on boar spermatozoa functions and the molecular mechanisms involved. Spermatozoa were exposed to the donor 3-morpholinosydnonimine (SIN-1) in non-capacitating or capacitating medium, motility was evaluated by CASA, functional parameters by flow cytometry and sperm protein phosphorylation by Western blotting. SIN-1 treatment, that significantly increases peroxynitrite levels in boar spermatozoa, potentiates the capacitating-stimulated phosphorylation of cAMP-dependent protein kinase 1 (PKA) substrates and GSK-3α. SIN-1 induced peroxynitrite does not decrease sperm viability, but significantly reduces sperm motility, progressive motility, velocities and motility coefficients. Concomitantly, peroxynitrite does not affect mitochondrial membrane potential, plasma membrane fluidity, or A23187-induced acrosome reaction. However, peroxynitrite significantly increases sperm lipid peroxidation in both media. In conclusion, peroxynitrite compromises boar sperm motility without affecting mitochondrial activity. Although peroxynitrite potentiates the phosphorylation of pathways leading to sperm motility, it also causes oxidative stress that might explain, at least partially, the motility impairment. physiologically by spermatozoa, generating peroxynitrite (ONOO − ) by a very fast and irreversible reaction [13] due to its exothermic nature [15]. In the same way, peroxynitrite can diffuse into the cells and even cross cell membranes and at low concentrations contribute to modulate sperm functions, mainly capacitation, as demonstrated in human spermatozoa [13] or in cryopreserved bovine spermatozoa, where ONOO − might also act as an inducer of sperm capacitation [16]. However, peroxynitrite molecule has been involved in some diseases (reviewed in [17]), because it is a strong oxidizing and/or nitrating agent that covalently binds to a variety of biomolecules causing lipid peroxidation, protein oxidation, nitration of the aromatic-side chains of amino acids as tyrosine and tryptophan, DNA oxidation, and inactivation of different enzymes. Therefore, ONOO − causes oxidative stress that promotes protein damage by direct oxidation of proteins side-chain, but also by adduction of secondary products resulting from the oxidation of polyunsaturated fatty acids, lipid peroxidation [18].The molecular and functional effects of nitrosative stress induced by high concentrations of ONOO − in spermatozoa have been mainly investigated in the human species [5,7,8,10,13,19], where ROS and RNS promote a dose dependent increase of sperm tyrosine-nitrated proteins and S-glutathionylation and impair sperm motility and capacitation [5,13]. Among negative eff...

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Relevance of peroxynitrite formation and 3-nitrotyrosine on spermatozoa physiology

Cited by 19 publications

References 96 publications

Macrophage-produced peroxynitrite induces antibiotic tolerance and supersedes intrinsic mechanisms of persister formation

Macrophage-produced peroxynitrite induces antibiotic tolerance and supersedes intrinsic mechanisms of persister formation

Male infertility: Role of vitamin D and oxidative stress markers

Molecular Mechanisms Involved in the Impairment of Boar Sperm Motility by Peroxynitrite-Induced Nitrosative Stress

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