Linoleic acid hydroperoxide reacts with hypochlorous acid, generating peroxyl radical intermediates and singlet molecular oxygen

Miyamoto, Sayuri; Martinez, Gláucia Regina; Rettori, Daniel; Augusto, Ohára; Medeiros, Marisa H. G.; Mascio, Paolo Di

doi:10.1073/pnas.0508170103

Cited by 119 publications

(111 citation statements)

References 67 publications

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“…Among the nutrients tested, VA, VC, VE, and Se enhanced HCV RNA replication, and these nutrients functioned as antioxidants. In contrast, four PUFAs inhibited HCV RNA replication, and they served as oxidants (29,44). These results are further evidence of the involvement of oxidative stress in HCV RNA replication.…”

Section: Vol 51 2007 Effects Of Ordinary Nutrients On Hcv Rna Replimentioning

confidence: 54%

Comprehensive Analysis of the Effects of Ordinary Nutrients on Hepatitis C Virus RNA Replication in Cell Culture

Yano

Ikeda

Abe

et al. 2007

Antimicrob Agents Chemother

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To date, only a limited number of studies have reported finding an influence of ordinary nutrients on hepatitis C virus (HCV) RNA replication. However, the effects of other nutrients on HCV RNA replication remain largely unknown. We recently developed a reporter assay system for genome-length HCV RNA replication in hepatoma-derived HuH-7 cells (OR6). Here, using this OR6 assay system, we comprehensively examined 46 nutrients from four nutrient groups: vitamins, amino acids, fatty acids, and salts. We found that three nutrients-␤-carotene, vitamin D 2 , and linoleic acid-inhibited HCV RNA replication and that their combination caused additive and/or synergistic effects on HCV RNA replication. In addition, combined treatment with each of the three nutrients and interferon alpha or beta or fluvastatin inhibited HCV RNA replication in an additive manner, while combined treatment with cyclosporine synergistically inhibited HCV RNA replication. In contrast, we found that vitamin E enhanced HCV RNA replication and negated the effects of the three anti-HCV nutrients and cyclosporine but not those of interferon or fluvastatin. These results will provide useful information for the treatment of chronic hepatitis C patients who also take anti-HCV nutrients as an adjunctive therapy in combination with interferon. In conclusion, among the ordinary nutrients tested, ␤-carotene, vitamin D 2 , and linoleic acid possessed anti-HCV activity in a cell culture system, and these nutrients are therefore considered to be potential candidates for enhancing the effects of interferon therapy.Hepatitis C virus (HCV) is a major pathogen of chronic hepatitis (CH) and leads to fatal liver diseases, such as liver cirrhosis and hepatocellular carcinoma (1,23,38). Approximately 170 million people worldwide are infected with HCV (40). Therefore, HCV infection is a global health problem. The combination of pegylated interferon (IFN) with ribavirin is currently the most effective therapy for CH C (11, 28), and long-term treatment has been shown to improve the sustained virological response (SVR) rate (37). However, the SVR rate still remains at approximately 55% (11). Combination therapy occasionally also causes adverse effects, such as severe anemia (10) and cerebral vascular lesions (7), and reduction of the dosage leads to insufficient treatment. These adverse effects are more serious in older patients. Therefore, it remains necessary to identify alternative agents that have fewer side effects to couple with IFN. In developing countries, it is difficult to administer expensive IFN therapy. Hence, in such countries, inexpensive anti-HCV reagents are especially desirable (36).The lack of a small-animal model and a cell culture system to support efficient HCV RNA replication hampered the development of anti-HCV reagents. Since an HCV subgenomic replicon system was developed in 1999 (25), the mechanism of HCV RNA replication has been gradually elucidated by a number of groups (2). However, this subgenomic replicon system may not necessarily reflect ...

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Section: Vol 51 2007 Effects Of Ordinary Nutrients On Hcv Rna Replimentioning

confidence: 54%

Comprehensive Analysis of the Effects of Ordinary Nutrients on Hepatitis C Virus RNA Replication in Cell Culture

Yano

Ikeda

Abe

et al. 2007

Antimicrob Agents Chemother

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“…This procedure is based on the oxidation of lipids by singlet molecular oxygen produced in an O 2 -saturated atmosphere using methylene blue as a photosensitizer. OAOOHs, LAOOHs, and ChOOHs were purified by flashcolumn chromatography and were quantified by iodometry (68). The hydroperoxide isomers were not separated among themselves, only from the parental lipids.…”

Section: Methodsmentioning

confidence: 99%

Ohr plays a central role in bacterial responses against fatty acid hydroperoxides and peroxynitrite

Alegria

Meireles

Cussiol

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Organic hydroperoxide resistance (Ohr) enzymes are unique Cysbased, lipoyl-dependent peroxidases. Here, we investigated the involvement of Ohr in bacterial responses toward distinct hydroperoxides. In silico results indicated that fatty acid (but not cholesterol) hydroperoxides docked well into the active site of Ohr from Xylella fastidiosa and were efficiently reduced by the recombinant enzyme as assessed by a lipoamide-lipoamide dehydrogenase-coupled assay. Indeed, the rate constants between Ohr and several fatty acid hydroperoxides were in the 10 7 -10 8 M −1 ·s −1 range as determined by a competition assay developed here. Reduction of peroxynitrite by Ohr was also determined to be in the order of 10 7 M −1 ·s −1 at pH 7.4 through two independent competition assays. A similar trend was observed when studying the sensitivities of a Δohr mutant of Pseudomonas aeruginosa toward different hydroperoxides. Fatty acid hydroperoxides, which are readily solubilized by bacterial surfactants, killed the Δohr strain most efficiently. In contrast, both wild-type and mutant strains deficient for peroxiredoxins and glutathione peroxidases were equally sensitive to fatty acid hydroperoxides. Ohr also appeared to play a central role in the peroxynitrite response, because the Δohr mutant was more sensitive than wild type to 3-morpholinosydnonimine hydrochloride (SIN-1 , a peroxynitrite generator). In the case of H 2 O 2 insult, cells treated with 3-amino-1,2,4-triazole (a catalase inhibitor) were the most sensitive. Furthermore, fatty acid hydroperoxide and SIN-1 both induced Ohr expression in the wildtype strain. In conclusion, Ohr plays a central role in modulating the levels of fatty acid hydroperoxides and peroxynitrite, both of which are involved in host-pathogen interactions.hydroperoxides | thiols | Cys-based peroxidase | pathogenic bacteria | Pseudomonas aeruginosa

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“…Many lines of evidence have linked the oxidative damage generated by these species with the development of pathological conditions, such as atherosclerosis, neurodegenerative diseases, and cancer [1]. Singlet molecular oxygen [O 2 ( 1 ⌬ g )] is a reactive form of oxygen that can be produced by the action of peroxidases [2,3], UVA light in the presence of a sensitizer [4,5] and also during the dimerization reactions of peroxyl radicals in lipid peroxidation [6,7]. Electron-rich biomolecules, such as lipids, proteins, and DNA, can be important targets for O 2 ( 1 ⌬ g ) oxidation [8].…”

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confidence: 99%

Characterization of O₂ (¹Δ_g)-derived oxidation products of tryptophan: A combination of tandem mass spectrometry analyses and isotopic labeling studies

Ronsein

Oliveira

Medeiros

et al. 2009

J. Am. Soc. Mass Spectrom.

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The fragmentation mechanisms of singlet oxygen [O 2 ( 1 ⌬ g )]-derived oxidation products of tryptophan (W) were analyzed using collision-induced dissociation coupled with 18 O-isotopic labeling experiments and accurate mass measurements. The five identified oxidized products, namely two isomeric alcohols (trans and cis WOH), two isomeric hydroperoxides (trans and cis WOOH), and N-formylkynurenine (FMK), were shown to share some common fragment ions and losses of small neutral molecules. Conversely, each oxidation product has its own fragmentation mechanism and intermediates, which were confirmed by 18 O-labeling studies. Isomeric WOH lost mainly H 2 O ϩ CO, while WOOH showed preferential elimination of C 2 H 5 NO 3 by two distinct mechanisms. Differences in the spatial arrangement of the two isomeric WOHs led to differences in the intensities of the fragment ions. The same behavior was also found for trans and cis WOOH. FMK was shown to dissociate by a diverse range of mechanisms, with the loss of ammonia the most favored route. MS/MS analyses, 18 O-labeling, and H 2 18 O experiments demonstrated the ability of FMK to exchange its oxygen atoms with water. Moreover, this approach also revealed that the carbonyl group has more pronounced oxygen exchange ability compared with the formyl group. The understanding of fragmentation mechanisms involved in O 2 ( 1 ⌬ g )-mediated oxidation of W provides a useful step toward the structural characterization of oxidized peptides and proteins. (J Am Soc Mass Spectrom 2009, 20, 188 -197)

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Linoleic acid hydroperoxide reacts with hypochlorous acid, generating peroxyl radical intermediates and singlet molecular oxygen

Cited by 119 publications

References 67 publications

Comprehensive Analysis of the Effects of Ordinary Nutrients on Hepatitis C Virus RNA Replication in Cell Culture

Comprehensive Analysis of the Effects of Ordinary Nutrients on Hepatitis C Virus RNA Replication in Cell Culture

Ohr plays a central role in bacterial responses against fatty acid hydroperoxides and peroxynitrite

Characterization of O₂ (¹Δ_g)-derived oxidation products of tryptophan: A combination of tandem mass spectrometry analyses and isotopic labeling studies

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Linoleic acid hydroperoxide reacts with hypochlorous acid, generating peroxyl radical intermediates and singlet molecular oxygen

Cited by 119 publications

References 67 publications

Comprehensive Analysis of the Effects of Ordinary Nutrients on Hepatitis C Virus RNA Replication in Cell Culture

Comprehensive Analysis of the Effects of Ordinary Nutrients on Hepatitis C Virus RNA Replication in Cell Culture

Ohr plays a central role in bacterial responses against fatty acid hydroperoxides and peroxynitrite

Characterization of O2 (1Δg)-derived oxidation products of tryptophan: A combination of tandem mass spectrometry analyses and isotopic labeling studies

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Characterization of O₂ (¹Δ_g)-derived oxidation products of tryptophan: A combination of tandem mass spectrometry analyses and isotopic labeling studies