621-44-3Relevant articles and documents
Scavengers for peroxynitrite: Inhibition of tyrosine nitration and oxidation with tryptamine derivatives, α-lipoic acid and synthetic compounds
Nakagawa, Hidehiko,Sumiki, Erika,Takusagawa, Mitsuko,Ikota, Nobuo,Matsushima, Yoshikazu,Ozawa, Toshihiko
, p. 261 - 265 (2000)
The inhibitory effects of various endogenous and synthetic compounds on the nitration and oxidation of L-tyrosine by peroxynitrite were examined. Nitrating and oxidizing activities were monitored by the formation of 3- nitrotyrosine and dityrosine with a HPLC-UV-fluorescence detector system, respectively. Glutathione, serotonin and synthetic sulfur- and selenium- containing compounds inhibited both the nitration and oxidation reaction of L-tyrosine effectively. However, 5-methoxytryptamine, melatonin and α-lipoic acid only inhibited the nitration reaction, and enhanced the formation of an oxidation product. This is important evidence that there are different intermediates in the nitrating and oxidizing reactions of L-tyrosine by peroxynitrite. It was suggested that 5-methoxytryptamine, melatonin and α- lipoic acid reacted only with the nitrating intermediate of peroxynitrite and inhibited nitration of L-tyrosine. Actually, the DNA strand breakage, which is believed to be a typical reaction of hydroxyl radical-like species, caused by peroxynitrite was not effectively inhibited by 5-methoxytryptamine. 5- Methoxytryptamine, melatonin and α-lipoic acid were viewed as useful reagents for investigating the mechanisms of damage by peroxynitrite in vitro.
Inhibition of nitrous acid-dependent tyrosine nitration and DNA base deamination by flavonoids and other phenolic compounds
Oldreive, Ceri,Zhao, Kaicun,Paganga, George,Halliwell, Barry,Rice-Evans, Catherine
, p. 1574 - 1579 (1998)
Exposure of tyrosine or DNA bases to acidic nitrite at low pH results in the nitration of tyrosine and the formation of base deamination products, respectively. At pH 1, hypoxanthine and xanthine are formed from the deamination of adenine and guanine, respectively, whereas under the same conditions, uracil is not detected. The yield of 3-nitrotyrosine derived from interaction of equimolar nitrite and tyrosine at pHI is approximately 50% of that obtained from equimolar peroxynitrite-tyrosine interactions at pH 7.4. The ability of a range of plant phenolic constituents to prevent damage mediated by acidic nitrite was also examined in comparison with the activity of vitamin C. The epicatechin/gallate family of flavonols, constituents of green tea, red wine, etc., demonstrates the most extensive inhibitory properties against both tyrosine nitration and base deamination. The results also show that ascorbic acid is a poor inhibitor of nitration or deamination under acidic conditions such as those of the stomach. The ability of plant phenolics to scavenge reactive nitrogen species derived from acidic nitrite may contribute to the protective effects of tea polyphenols against gastric cancer.
pH-Dependent Nitrotyrosine Formation in Ribonuclease A is Enhanced in the Presence of Polyethylene Glycol (PEG)
Roy, Pritam,Panda, Atashi,Hati, Sumon,Dasgupta, Swagata
, p. 4780 - 4792 (2019)
Protein nitration can occur as a result of peroxynitrite-mediated oxidative stress. Excess production of peroxynitrite (PN) within the cellular medium can cause oxidative damage to biomolecules. The in vitro nitration of Ribonuclease A (RNase A) results in nitrotyrosine (NT) formation with a strong dependence on the pH of the medium. In order to mimic the cellular environment in this study, PN-mediated RNase A nitration has been carried out in a crowded medium. The degree of nitration is higher at pH 7.4 (physiological pH) compared to pH 6.0 (tumor cell pH). The extent of nitration increases significantly when PN is added to RNase A in the presence of crowding agents PEG 400 and PEG 6000. PEG has been found to stabilize PN over a prolonged period, thereby increasing the degree of nitration. NT formation in RNase A also results in a significant loss in enzymatic activity.
Functional hybrids of layered double hydroxides with hemin: Synergistic effect for peroxynitrite-scavenging activity
Qiao, Fengmin,Shi, Weijie,Dong, Jing,Lv, Wei,Ai, Shiyun
, p. 44614 - 44620 (2014)
Hemin has been successfully modified onto the surface of CuAl layered double hydroxide nanosheets by a simple coprecipitation process, which afforded a hemin modified CuAl layered double hydroxide (H-LDH) hybrid functional material that exhibited protective effects against the harmful ONOO-. The obtained products were characterized by X-ray powder diffraction, scanning electron microscopy, transmission electron microscopy and Fourier transform infrared spectroscopy, which showed that the samples had hexagonal symmetry structure with a mean lateral size of 1 μm, on the surface of which were adsorbed round particles with a diameter of about 300 nm. A detailed inhibition study on ONOO--mediated nitration reactions indicated that the interaction between hemin and LDHs results in a synergistic effect, which leads to an efficient reduction of ONOO- to nitrate. The present study suggests that the H-LDHs had an efficient ONOO- scavenging ability, and may well be a potent ONOO- scavenger for protection of the cellular defense activity against ONOO- involved diseases.
Tyrosine nitration in peptides by peroxynitrite generated in situ in a light-controlled platform: Effects of pH and thiols
Deboer, Tara R.,Palomino, Rafael I.,Idiga, Sharon O.,Millhauser, Glenn L.,Mascharak, Pradip K.
, p. 24 - 30 (2014)
Peroxynitrite has been shown to play a critical role in inflammation and affords 3-nitrotyrosine as the hallmark product. The reported methods of generating this reactive nitrogen species in situ often fails to provide a high and steady flux of peroxynitrite resulting in poor yields of 3-nitrotyrosine. Herein we report a two-component peroxynitrite-generating platform in which this anion is produced in a biomimetic fashion and under the control of visible light. Incorporation of the nitric oxide- and superoxide-generating components in polymer matrices allows easy alterations of pH in the reaction wells of this platform. We have demonstrated very efficient nitration of tyrosine by peroxynitrite at different pH values and with varying concentrations of carbonate. In addition to tyrosine, a set of tyrosine-containing peptides was also studied. Presence of glutathione in the reaction wells increases the extent of tyrosine nitration in such peptide substrates presumably by raising the lifetime of nitric oxide in the reaction medium. When a cysteine residue was included in the sequence of the peptide, the extent of nitration of the tyrosine residue was found to depend on the position of the cysteine residue with respect to tyrosine. The extent of tyrosine nitration is strongly attenuated when the cysteine residue is directly adjacent to the tyrosine. This effect has been attributed to an intramolecular radical transfer mechanism. Taken together, results of this study demonstrate the potential of this light-controlled platform as a convenient bioanalytical tool in studying the reactions of peroxynitrite under widely varying conditions.
Effects of oxygen on the reactivity of nitrogen oxide species including peroxynitrite
Kikugawa, Kiyomi,Hiramoto, Kazuyuki,Ohkawa, Takumi
, p. 17 - 23 (2004)
This paper describes the O2-dependent control of the reactivity of nitrogen oxide species for the production of biologically important nitrated and nitrosated compounds. In this study, the effects of O2 on the reactivity of NO, NO2, and ONOO-/ONOOH for nitration of tyrosine (Tyr) and nitrosation of glutathione (GSH) and morpholine (MOR) were examined. NO produced S-nitrosoglutathione (GSNO) and N-nitrosomorpholine (NMOR) through the formation of N2O3 under aerobic conditions, and NO2 produced 3-nitrotyrosine (3-NO2Tyr), GSNO, and NMOR. Transnitrosation from GSNO to MOR was observed only in the presence of O2. Although preformed ONOO-/ONOOH produced all the products under aerobic conditions, the formation of 3-NO2Tyr and GSNO was markedly reduced and the formation of NMOR was enhanced under anaerobic conditions. The reactivity of the CO2 adduct of ONOO- was similarly dependent on O2. 3-NO2Tyr was produced effectively by reaction with ONOO-/ONOOH at the O2 concentration of 270 μM and by reaction with its CO2 adduct at O2 concentrations greater than 5 μM. Generation of·OH from ONOO-/ONOOH was suppressed under anaerobic conditions. The reactivity of ONOO-/ONOOH and·OH generation from ONOO- were reversibly controlled by the O2 concentration.
Dietary Dityrosine Induces Mitochondrial Dysfunction by Diminished Thyroid Hormone Function in Mouse Myocardia
Ge, Yueting,Li, Bowen,Lu, Yipin,Ma, Shuhua,Ren, Haoyi,Tang, Xue,Xu, Ying,Yang, Shaojun,Zhang, Kai,Zhao, Qi
, p. 9223 - 9234 (2020/10/13)
Oxidized tyrosine products (OTP) have been detected in commercial foods with high protein content, such as meat and milk products. OTP intake induces tissue oxidative stress and affects the normal activity of the hypothalamic-pituitary-thyroid axis (HPT). This study aims to investigate the effects of OTP and their main product, dityrosine (Dityr), on mouse myocardial function and myocardial energy metabolism. Mice received daily intragastric administration of either tyrosine (Tyr; 420 μg/kg body weight), Dityr (420 μg/kg body weight), or OTP (1909 μg/kg body weight) for 35 days. Additionally, H9c2 cells were incubated with various concentrations of Dityr for 72 h. We found that OTP and pure Dityr induced oxidative stress in growing mice and in H9c2 cells, resulting in a redox state imbalance, myocardial injury, mitochondrial dysfunction, and energy metabolism disorder. Dityr interferes with T3 regulation of the myocardium via the PI3K/AKT/GSK3β pathway, leading to myocardial mitochondrial damage and energy metabolism disorders. Food-borne OTP, especially Dityr, can disrupt thyroid hormone function in mouse myocardia leading to mitochondrial dysfunction, energy metabolism disorder, and oxidative stress.
