Bicarbonate Plays a Critical Role in the Generation of Cytotoxicity during SIN-1 Decomposition in Culture Medium

Shirai, Kyo; Okada, Tatsunori; Konishi, Kanako; Murata, Hiroshi; Akashi, Soichiro; Sugawara, Fumio; Watanabe, Nobuo; Arai, Takao

doi:10.1155/2012/326731

Cited by 5 publications

(6 citation statements)

References 35 publications

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“…However, very similar cytotoxic effects supporting our observations were reported in the case of neural PC12 cells exposed to peroxynitrite generated during oxidation of 3-morpholinisydnonimide (SIN-1) (Konishi et al, 2009; Shirai et al, 2012). The exposure of cells to the culture medium obtained after complete SIN-1 decomposition demonstrates almost the same level of cytotoxicity as fresh SIN-1.…”

Section: Discussionsupporting

confidence: 90%

“…The authors concluded that the formation of toxicants is a result of the simultaneous formation of NO and superoxide. In agreement with our considerations regarding the mechanism of peroxynitrite reactivity, it was found that CO 2 plays a critical role in the cytotoxicity of the SIN-1 decomposition products (Shirai et al, 2012). Surprisingly, the authors misinterpreted the effect of BSA when they found that addition of fresh serum (or BSA) antagonizes the cytotoxicity.…”

Section: Discussionsupporting

confidence: 90%

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Bacillus anthracis co-opts nitric oxide and host serum albumin for pathogenicity in hypoxic conditions

John¹,

Blower²,

Popova³

et al. 2013

Front. Cell. Infect. Microbiol.

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Bacillus anthracis is a dangerous pathogen of humans and many animal species. Its virulence has been mainly attributed to the production of Lethal and Edema toxins as well as the antiphagocytic capsule. Recent data indicate that the nitric oxide (NO) synthase (baNOS) plays an important pathogenic role at the early stage of disease by protecting bacteria from the host reactive species and S-nytrosylating the mitochondrial proteins in macrophages. In this study we for the first time present evidence that bacteria-derived NO participates in the generation of highly reactive oxidizing species which could be abolished by the NOS inhibitor L - NAME, free thiols, and superoxide dismutase but not catalase. The formation of toxicants is likely a result of the simultaneous formation of NO and superoxide leading to a labile peroxynitrite and its stable decomposition product, nitrogen dioxide. The toxicity of bacteria could be potentiated in the presence of bovine serum albumin. This effect is consistent with the property of serum albumin to serves as a trap of a volatile NO accelerating its reactions. Our data suggest that during infection in the hypoxic environment of pre-mortal host the accumulated NO is expected to have a broad toxic impact on host cell functions.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

Bacillus anthracis co-opts nitric oxide and host serum albumin for pathogenicity in hypoxic conditions

John¹,

Blower²,

Popova³

et al. 2013

Front. Cell. Infect. Microbiol.

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“…Next, fluorescence imaging was carried out for intracellular ONOO – . Cells were pretreated with 3-morpholinosydnonimine hydrochloride (SIN-1, a known ONOO – donor); in a control group, uric acid (UA, a known ONOO – scavenger) was pretreated with cells to quench ONOO – . We observed that when cells were pretreated with SIN-1, the fluorescence of the probe in both HepG2 (Figure ) and RAW 264.7 (Figure S5) cells enhanced significantly with respect to the control group.…”

Section: Resultsmentioning

confidence: 95%

A Highly Sensitive and Selective Near-Infrared Fluorescent Probe for Imaging Peroxynitrite in Living Cells and Drug-Induced Liver Injury Mice

Chai

Chen

et al. 2023

Anal. Chem.

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Drug-induced liver injury (DILI) is a major clinical issue associated with the majority of commercial drugs. During DILI, the peroxynitrite (ONOO–) level is upregulated in the liver. However, traditional methods are unable to timely monitor the dynamic changes of the ONOO– level during DILI in vivo. Therefore, ONOO–-activated near-infrared (NIR) fluorescent probes with high sensitivity and selectivity are key to the early diagnosis of DILI in situ. Herein, we report a novel ONOO–-responsive NIR fluorescent probe, QCy7-DP, which incorporates a donor-dual-acceptor π-electron cyanine skeleton with diphenyl phosphinate. The ONOO–-mediated highly selective hydrolytic cleavage via an addition-elimination pathway of diphenyl phosphinate produced the deprotonated form of QCy7 in physiological conditions with a distinctive extended conjugated π-electron system and ∼200-fold enhancement in NIR fluorescence emission at 710 nm. Moreover, the probe QCy7-DP was successfully used for the imaging of the endogenous and exogenous ONOO– concentration changes in living cells. Importantly, in vivo fluorescence imaging tests demonstrated that the probe can effectively detect the endogenous generation of ONOO– in an acetaminophen (APAP)-induced liver injury mouse model. This study provides insight into the design of highly selective NIR fluorescent probes suitable for spatiotemporal monitoring of ONOO– under different pathological conditions.

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“…The reaction was run at 30-min intervals for three trials. The oxygen consumption was expressed as percentage of oxygen consumed [19]. The reagents were mixed according to the following experimental conditions: 1…”

Section: Measurement Of Oxygen Consumptionmentioning

confidence: 99%

“…4b). It has become increasingly evident that carbon dioxide plays a critical role in the formation of the peroxynitrite during SIN-1 auto-oxidation as it can directly react with peroxynitrite [19]. Thus, we further examined the effects of bicarbonate on SIN-1-mediated oxygen consumption in the presence of 5-ASA.…”

Section: Statistical Analysesmentioning

confidence: 99%

Protection against peroxynitrite-induced DNA damage by mesalamine: implications for anti-inflammation and anti-cancer activity

Graham

Li²,

Dou

et al. 2013

Mol Cell Biochem

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Mesalamine (5-aminosalicylic acid, 5-ASA) is known to be the first-line medication for treatment of patients with ulcerative colitis. Studies have demonstrated that ulcerative colitis patients treated with 5-ASA have an overall decrease in the risk of developing colorectal carcinoma. However, the mechanisms underlying 5-ASA-mediated anti-inflammatory and anti-cancer effects are yet to be elucidated. Because peroxynitrite has been critically involved in inflammatory stress and carcinogenesis, this study was undertaken to investigate the effects of 5-ASA in peroxynitrite-induced DNA strand breaks, an important event leading to peroxynitrite-elicited cytotoxicity. Incubation of φX-174 plasmid DNA with the peroxynitrite generator 3-morpholinosydnonimine (SIN-1) led to the formation of both single- and double-stranded DNA breaks in a concentration-dependent manner. The presence of 5-ASA at 0.1 and 1.0 mM was found to significantly inhibit SIN-1-induced DNA strand breaks in a concentration-dependent manner. The consumption of oxygen induced by SIN-1 was found to not be affected by 5-ASA at 0.1-50 mM, indicating that 5-ASA at these concentrations is not involved in the auto-oxidation of SIN-1 to form peroxynitrite. It is observed that 5-ASA at 0.1-1 mM showed considerable inhibition of peroxynitrite-mediated luminol chemiluminescence in a dose-dependent fashion, suggesting that 5-ASA is able to directly scavenge the peroxynitrite. Electron paramagnetic resonance (EPR) spectroscopy in combination with spin-trapping experiments, using 5,5-dimethylpyrroline-N-oxide (DMPO) as spin trap resulting in the formation of DMPO-hydroxyl radical adduct from peroxynitrite, and 5-ASA only at higher concentration (1 mM) inhibited the hydroxyl radical adduct while shifting EPR spectra, indicating that 5-ASA at higher concentrations may generate a more stable free radical species rather than acting purely as a hydroxyl radical scavenger. Taken together, these studies demonstrate for the first time that 5-ASA can potently inhibit peroxynitrite-mediated DNA strand breakage, scavenge peroxynitrite, and affect peroxynitrite-mediated radical formation, which may be responsible, at least partially, for its anti-inflammatory and anti-cancer effects.

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Bicarbonate Plays a Critical Role in the Generation of Cytotoxicity during SIN-1 Decomposition in Culture Medium

Cited by 5 publications

References 35 publications

Bacillus anthracis co-opts nitric oxide and host serum albumin for pathogenicity in hypoxic conditions

Bacillus anthracis co-opts nitric oxide and host serum albumin for pathogenicity in hypoxic conditions

A Highly Sensitive and Selective Near-Infrared Fluorescent Probe for Imaging Peroxynitrite in Living Cells and Drug-Induced Liver Injury Mice

Protection against peroxynitrite-induced DNA damage by mesalamine: implications for anti-inflammation and anti-cancer activity

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