Mechanistic insight into the peroxidase catalyzed nitration of tyrosine derivatives by nitrite and hydrogen peroxide

Monzani, Enrico; Roncone, Raffaella; Galliano, Monica; Koppenol, Willem H.; Casella, Luigi

doi:10.1111/j.1432-1033.2004.03992.x

Cited by 58 publications

(75 citation statements)

References 40 publications

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“…Based on the chemical analyses of the intermediate products of MPO activity on nitrite and hydrogen peroxide as substrates, nitrogen dioxide, a powerful oxidizing species, has been proposed to be the most likely reaction product, and a second pathway that would generate peroxynitrite, although possible, was thought to play a minor role (23). Recent experiments argue that both pathways (generating nitrogen dioxide or peroxynitrite) operate simultaneously and can both play significant roles in vivo (24).…”

Section: Discussionmentioning

confidence: 99%

Inducible Peroxidases Mediate Nitration of Anopheles Midgut Cells Undergoing Apoptosis in Response to Plasmodium Invasion

Kumar

Gupta

Han

et al. 2004

Journal of Biological Chemistry

119

134

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Plasmodium berghei invasion of Anopheles stephensi midgut cells causes severe damage, induces expression of nitric-oxide synthase, and leads to apoptosis. The present study indicates that invasion results in tyrosine nitration, catalyzed as a two-step reaction in which nitric-oxide synthase induction is followed by increased peroxidase activity. Ookinete invasion induced localized expression of peroxidase enzymes, which catalyzed protein nitration in vitro in the presence of nitrite and H 2 O 2 . Histochemical stainings revealed that when a parasite migrates laterally and invades more than one cell, the pattern of induced peroxidase activity is similar to that observed for tyrosine nitration. In Anopheles gambiae, ookinete invasion elicited similar responses; it induced expression of 5 of the 16 peroxidase genes predicted by the genome sequence and decreased mRNA levels of one of them. One of these inducible peroxidases has a C-terminal oxidase domain homologous to the catalytic moiety of phagocyte NADPH oxidase and could provide high local levels of superoxide anion (O 2 . ), that when dismutated would generate the local increase in H 2 O 2 required for nitration. Chemically induced apoptosis of midgut cells also activated expression of four ookinete-induced peroxidase genes, suggesting their involvement in general apoptotic responses. The two-step nitration reaction provides a mechanism to precisely localize and circumscribe the toxic products generated by defense reactions involving nitration. The present study furthers our understanding of the biochemistry of midgut defense reactions to parasite invasion and how these may influence the efficiency of malaria transmission by anopheline mosquitoes.Anopheline mosquitoes are the natural vectors of human malaria worldwide. When a female mosquito takes a blood meal from a malaria-infected host, the ingested Plasmodium gametocytes complete their differentiation into mature gametes in the midgut lumen. Following fertilization, zygotes mature into motile ookinetes, which traverse the midgut epithelium and form oocysts in the space between the epithelial cells and the basal lamina. Oocysts grow, mature, and eventually rupture, releasing a large number of sporozoites into the hemolymph. The sporozoites invade the salivary glands and are injected into a new vertebrate host when an infected female takes a second blood meal.In Anopheles stephensi, midgut invasion of Plasmodium berghei ookinetes takes place around 24 h after blood feeding and induces the expression of nitric-oxide synthase (NOS) 1 as revealed by immunofluorescence (1) and increased NADPHdependent nitroblue tetrazolium reduction activity (2). NOS catalyzes the formation of nitric oxide (NO), a highly reactive and toxic molecule (3-5). NO is unstable and reacts readily with other molecules, generating multiple reactive nitrogen intermediates. Peroxynitrite is formed by a rapid reaction between NO and a superoxide anion and readily nitrates proteins in vitro (6, 7). peroxynitrite has also been proposed to be t...

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Section: Discussionmentioning

confidence: 99%

Inducible Peroxidases Mediate Nitration of Anopheles Midgut Cells Undergoing Apoptosis in Response to Plasmodium Invasion

Kumar

Gupta

Han

et al. 2004

Journal of Biological Chemistry

119

134

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“…Kumar et al [39] hypothesized that · NO synthesis following parasite infection in An. gambiae results in accumulation of nitrite, which is a substrate for myeloperoxidase (MPO)-mediated tyrosine nitration [43]. However, all of these reactive pathways rely on the formation of higher NO x and thus NTYR can be considered a marker of nitrative stress.…”

Section: Ntyr Formation In the A Stephensi Midgutmentioning

confidence: 99%

Nitric oxide metabolites induced in Anopheles stephensi control malaria parasite infection

Peterson

Gow

Luckhart

2007

Free Radical Biology and Medicine

100

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Malaria parasite infection in anopheline mosquitoes is limited by inflammatory levels of nitric oxide metabolites. To assess the mechanisms of parasite stasis or toxicity, we investigated the biochemistry of these metabolites within the blood-filled mosquito midgut. Our data indicate that nitrates, but not nitrites, are elevated in the Plasmodium-infected midgut. Although levels of S-nitrosothiols do not change with infection, blood proteins are S-nitrosylated after ingestion by the mosquito. In addition, photolyzable nitric oxide, which can be attributed to metal nitrosyls, is elevated following infection and, based on the abundance of hemoglobin, likely includes heme iron nitrosyl. The persistance of oxyhemoglobin throughout blood digestion and changes in hemoglobin conformation in response to infection suggest that hemoglobin catalyzes the synthesis of nitric oxide metabolites in a reducing environment. Provision of urate, a potent reductant and scavenger of oxidants and nitrating agents, as a dietary supplement to mosquitoes increased parasite infection levels relative to allantoin-fed controls, suggesting that nitrosative and/or oxidative stresses negatively impact developing parasites. Collectively, our results reveal a unique role for nitric oxide in an oxyhemoglobin-rich environment. In contrast to facilitating oxygen delivery by hemoglobin in the mammalian vasculature, nitric oxide synthesis in the blood-filled mosquito midgut drives the formation of toxic metabolites that limit parasite development.

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“…Note that CO 3 2 and NO 2 are stronger oxidant species than peroxynitrite (50,65). The comparison of globin and peroxidase action (see Tables 5, 6 Peroxidation of classical peroxidase substrates (e.g., phenols) by globins occurs at a much slower rate, with respect to the heme-enzymes (24,48,58). The different catalytic behavior of globins and peroxidases for different substrates might be due to the strong hydrogen bond present in peroxidases between the proximal histidyl residue and a conserved aspartate residue (45).…”

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confidence: 99%

Catalytic peroxidation of nitrogen monoxide and peroxynitrite by globins

et al. 2008

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SummaryGlobins are generally considered as carriers of diatomic gaseous ligands (e.g., O 2 and NO) in metazoa. Recently, the (pseudo-)enzymatic activity of globins towards reactive nitrogen and oxygen species has been elucidated. In particular, some globins (e.g., hemoglobin and myoglobin) catalyze the enzymatic scavenging of NO and peroxynitrite in the presence of H 2 O 2 . Indeed, H 2 O 2 oxidizes some globins leading to the formation of water and of the heme-protein ferryl derivative, which, in turn, oxidizes NO and peroxynitrite leading to the formation of the globin ferric species, NO 2 2 , and NO 3 2 . Here, we hypothesize that NO, peroxynitrite, and H 2 O 2 are co-substrates for the peroxidase activity of some globins, this catalytic activity was reported in 1900 for the first time, even though the substrates have never been identified firmly up to now. The hemoglobin (Hb) superfamily includes several hemeproteins, generally referred to as globins, which are found in all kingdoms of living organisms (1, 2). Globin functions have been the subject of active debate, in addition to dioxygen transport and storage. Several functions have been proposed recently, including control of nitrogen monoxide levels, O 2 sensing, and dehaloperoxidase activity (3-15).Globins share physical, spectroscopic, and chemical similarities with peroxidases (16,17). In fact, as demonstrated first in 1900 (18), Hb reacts readily with hydrogen peroxide (H 2 O 2 ). In 1923, the peroxidase activity of Hb has been reported (19), and in 1938, the modulation of the peroxidase activity of Hb by haptoglobin has been demonstrated (20). The reaction of myoglobin (Mb) with H 2 O 2 , on the other hand, apparently was not considered until 1952 (21), and the ability of Mb to catalyze peroxide oxidation of substrates was not reported until 1955 (22). Upon reaction with H 2 O 2 , Mb and Hb form the cytotoxic ferryl derivative (heme-Fe(IV)¼ ¼O), which is similar to compound II formed by peroxidases (23, 24). Heme-Fe(IV)¼ ¼O is able to oxidize a wide range of reducing substrates, such as phenols and aromatic amines, even though substrate peroxidation by Hb and Mb is far less efficient than that of peroxidases (24, 25), ruling out the possibility that the potential peroxidase activity of Hb and Mb is exerted on this class of substrates under normal conditions.Here, we hypothesize that the capability of some globins (e.g., Hb and Mb) to form a compound II-like species under oxidative stress may be actually exploited to avoid the building up of NO and peroxynitrite, 1 which can be then identified as the 'true' substrates for the peroxidase activity of Hb and Mb.Heme-proteins share the ability of detoxifying nitrogen reactive species, for example, NO. Even though leukocyte peroxi- 1 The term peroxynitrite is used in the text to refer generically to both ONOO 2 and its conjugated acid HOONO (38).

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Mechanistic insight into the peroxidase catalyzed nitration of tyrosine derivatives by nitrite and hydrogen peroxide

Cited by 58 publications

References 40 publications

Inducible Peroxidases Mediate Nitration of Anopheles Midgut Cells Undergoing Apoptosis in Response to Plasmodium Invasion

Inducible Peroxidases Mediate Nitration of Anopheles Midgut Cells Undergoing Apoptosis in Response to Plasmodium Invasion

Nitric oxide metabolites induced in Anopheles stephensi control malaria parasite infection

Catalytic peroxidation of nitrogen monoxide and peroxynitrite by globins

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