Peroxynitrite Formation and Detection in Living Cells

Ríos, Natalia; Prolo, Carolina; Álvarez, María Noel; Piacenza, Lucı́a; Radí, Rafael

doi:10.1016/b978-0-12-804273-1.00021-1

Cited by 11 publications

(13 citation statements)

References 146 publications

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“…24,36 The PN flux generated in phagosomes can reach 50−100 μM/min in the case of the immune response, while the average flux in arterial endothelial cells is as low as about 6 μM/min. 40 In the experiments, SIN-1 can continue to produce PN for a certain period of time, with a flux rate of near 0.01fold SIN-1 concentration under physiological conditions. 41 The resulting LD 50 and LD 80 of SIN-1 are 14.1 ± 2.1 and 61.8 ± 5.6 μM/min toward the S + strain, higher than the values of 6.7 ± 1.3 and 40.7 ± 4.2 μM/min toward the S − strain; moreover, the lethal doses are in the boundary range of PN in human body (Table S2).…”

Section: ■ Discussionmentioning

confidence: 94%

“…10 It should be noted that H 2 O 2 , HOCl, and PN are the three essential oxidant molecules in the immune response of living organisms, of which H 2 O 2 and HOCl are mainly produced by neutrophils and PN is produced primarily by macrophages. 37,38,40 H 2 O 2 generates OH • under metal catalysis through the Fenton reaction, 10 and PN can generate OH • after protonation under a specific pH value. 15,60,61 PT-DNA seems more helpful in the resistance to H 2 O 2 and PN but not to HOCl.…”

Section: ■ Discussionmentioning

confidence: 99%

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Defense Mechanism of Phosphorothioated DNA under Peroxynitrite-Mediated Oxidative Stress

Huang

Shi

et al. 2020

ACS Chem. Biol.

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DNA phosphorothioation (PT) exists in many pathogenic bacteria; however, the mechanism of PT-DNA resistance to the immune response is unclear. In this work, we meticulously investigated the peroxynitrite (PN) tolerance using PT-bioengineered E. coli strains. The in vivo experiment confirms that the S + strain survives better than the S − strain under moderately oxidative stress. The LCMS, IC, and GCMS experiments demonstrated that phosphorothioate partially converted to phosphate, and the byproduct included sulfate and elemental sulfur. When O,O-diethyl thiophosphate ester (DETP) was used, the reaction rate k 1 was determined to be 4.3 ± 0.5 M −1 s −1 in the first-order for both phosphorothioate and peroxynitrite at 35 °C and pH of 8.0. The IC 50 values of phosphorothioate dinucleotides are dramatically increased by 400−700-fold compared to DETP. The SH/OH Yin-Yang mechanism rationalizes the in situ DNA self-defense against PN-mediated oxidative stress at the extra bioenergetic cost of DNA modification.

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Section: ■ Discussionmentioning

confidence: 94%

Section: ■ Discussionmentioning

confidence: 99%

Defense Mechanism of Phosphorothioated DNA under Peroxynitrite-Mediated Oxidative Stress

Huang

Shi

et al. 2020

ACS Chem. Biol.

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“…ONOO − , as a representative ROS with high oxidizing capacities in living systems, is the reaction product of superoxide radical anion and nitric oxide. 25 ONOO − is considered as one of the most potent toxin ROS, which, in concert with other ROS, triggers mitochondrial dysfunction and dysregulates mitophagy. 5,26−28 For example, it has been reported that ONOO − can induce dynamin-related protein 1 (Drp1) recruitment through nitration, leading to mitochondrial damage, subsequently triggering PINK1/Parkinmediated mitophagy activation.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Activity-Based Fluorescent Molecular Logic Gate Probe for Dynamic Tracking of Mitophagy Induced by Oxidative Stress

et al. 2021

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Visualizing and modulating the mitophagy process is essential for understanding the role of mitophagy in cellular homeostasis, physiology, and pathology. To overcome the sensing limitation of available mitophagy probes to only lysosome fusion or degradation, a molecular logic gate probe showing multiple fluorescence responses to different mitophagy stages was proposed in this study to sense the oxidative stress-induced mitophagy via a dual-channel mode. This new fluorescent molecular logic gate probe, Mito-PN, was composed by integrating a peroxynitrite-responsive 1,8-naphthalimide with an acidity-activatable rhodamine spirolactam and possesses the mitochondria-targeting capability due to its triphenylphosphonium group. This probe is able to sense both the mitophagy initiation triggered by peroxynitrite and lysosome fusion at different fluorescence wavelengths. It can be rapidly activated by mitochondrial peroxynitrite to turn on the green fluorescence of naphthalimide, and subsequent lysosome/mitophagosome fusion activates the probe with protons to generate red fluorescence. Moreover, our preliminary results demonstrate that the fluorescence response of Mito-PN to peroxynitrite-induced mitophagy can be discriminated from the mitophagy stimulated by carbonyl cyanide m-chlorophenyl hydrazone, which further proves the specific mitophagy tracking ability of Mito-PN. Overall, this research offers a potentially powerful tool for studying the role played by peroxynitrite in mitophagy and provides a versatile strategy for monitoring oxidative stress-related pathological processes.

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“…Hypoxia induces the regulation of some isoforms of nitric oxide synthase and the release of nitric oxide radicals (NO • ) [ 81 , 82 , 83 ]. Excess production of nitric oxide is detrimental when it reacts with superoxide to form large amounts of peroxynitrite (ONOO − ) [ 84 , 85 , 86 ]. In healthy cells, low levels of ONOO − are beneficial and regulate apoptosis.…”

Section: Hypoxia-mediated Pathophysiological Changes In the Tumor Mic...mentioning

confidence: 99%

Dual-Mode Tumor Imaging Using Probes That Are Responsive to Hypoxia-Induced Pathological Conditions

et al. 2022

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Hypoxia in solid tumors is associated with poor prognosis, increased aggressiveness, and strong resistance to therapeutics, making accurate monitoring of hypoxia important. Several imaging modalities have been used to study hypoxia, but each modality has inherent limitations. The use of a second modality can compensate for the limitations and validate the results of any single imaging modality. In this review, we describe dual-mode imaging systems for the detection of hypoxia that have been reported since the start of the 21st century. First, we provide a brief overview of the hallmarks of hypoxia used for imaging and the imaging modalities used to detect hypoxia, including optical imaging, ultrasound imaging, photoacoustic imaging, single-photon emission tomography, X-ray computed tomography, positron emission tomography, Cerenkov radiation energy transfer imaging, magnetic resonance imaging, electron paramagnetic resonance imaging, magnetic particle imaging, and surface-enhanced Raman spectroscopy, and mass spectrometric imaging. These overviews are followed by examples of hypoxia-relevant imaging using a mixture of probes for complementary single-mode imaging techniques. Then, we describe dual-mode molecular switches that are responsive in multiple imaging modalities to at least one hypoxia-induced pathological change. Finally, we offer future perspectives toward dual-mode imaging of hypoxia and hypoxia-induced pathophysiological changes in tumor microenvironments.

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Peroxynitrite Formation and Detection in Living Cells

Cited by 11 publications

References 146 publications

Defense Mechanism of Phosphorothioated DNA under Peroxynitrite-Mediated Oxidative Stress

Defense Mechanism of Phosphorothioated DNA under Peroxynitrite-Mediated Oxidative Stress

Activity-Based Fluorescent Molecular Logic Gate Probe for Dynamic Tracking of Mitophagy Induced by Oxidative Stress

Dual-Mode Tumor Imaging Using Probes That Are Responsive to Hypoxia-Induced Pathological Conditions

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