Role of peroxynitrite in macrophage microbicidal mechanisms in vivo revealed by protein nitration and hydroxylation

Linares, Edlaine; Giorgio, Selma; Mortara, Renato Arruda; Santos, Célio X.C.; Yamada, Áureo T.; Augusto, Ohára

doi:10.1016/s0891-5849(01)00516-0

Cited by 112 publications

(89 citation statements)

References 45 publications

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“…Work from our group has demonstrated that peroxynitrite impairs the antioxidant defenses (18) as well as the energy and calcium metabolism of cultured epimastigotes and reduces their motility and replication rates (38). In agreement with this idea, Linares et al (39) showed that peroxynitrite is the molecule responsible for the resistance of C57BL/ 6 mice to L. amazonensis infection. In addition, by affecting tyrosine phosphorylation pathways, peroxynitrite is able to modulate the activation and proliferation of T lymphocytes (28).…”

Section: Discussionsupporting

confidence: 53%

Protein 3-nitrotyrosine formation during Trypanosoma cruzi infection in mice

Naviliat

Gualco

Cayota

et al. 2005

Braz J Med Biol Res

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Tyrosine nitration is a post-translational modification resulting from the addition of a nitro (-NO 2 ) group to the ortho-position of tyrosine residues. Detection of protein 3-nitrotyrosine is regarded as a marker of nitro-oxidative stress and is observed in inflammatory processes. The formation and role of nitrating species in the control and myocardiopathy of T. cruzi infection remain to be studied. We investigated the levels of • NO and protein 3-nitrotyrosine in the plasma of C3H and BALB/c mice and pharmacologically modulated their production during the acute phase of T. cruzi infection. We also looked for protein 3-nitrotyrosine in the hearts of infected animals. Our results demonstrated that C3H animals produced higher amounts of • NO than BALB/c mice, but their generation of peroxynitrite was not proportionally enhanced and they had higher parasitemias. While N G -nitroarginine methyl ester treatment abolished • NO production and drastically augmented the parasitism, mercaptoethylguanidine and guanidoethyl disulfide, at doses that moderately reduced the • NO and 3-nitrotyrosine levels, paradoxically diminished the parasitemia in both strains. Nitrated proteins were also demonstrated in myocardial cells of infected mice. These data suggest that the control of T. cruzi infection depends not only on the capacity to produce • NO, but also on its metabolic fate, including the generation of nitrating species that may constitute an important element in parasite resistance and collateral myocardial damage.

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Section: Discussionsupporting

confidence: 53%

Protein 3-nitrotyrosine formation during Trypanosoma cruzi infection in mice

Naviliat

Gualco

Cayota

et al. 2005

Braz J Med Biol Res

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“…The (MGD) 2 Fe(II) complex was prepared immediately before each experiment by adding FeSO 4 powder to a concentrated solution of MGD in 20 mM sodium citrate [22]. The concentration of the (MGD) 2 Fe(II) nitrosyl complex was estimated by EPR spectra double integration as previously described [23,24].…”

Section: Epr Measurementsmentioning

confidence: 99%

Nitrite as the major source of nitric oxide production by Arabidopsis thaliana in response to Pseudomonas syringae

et al. 2005

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Å NO production in Arabidopsis thaliana in response to Pseudomonas syringae pv maculicola. NOS activity increased substantially in leaves inoculated with P. syringae. However, electron paramagnetic resonance experiments showed a much higher Å NO formation that was dependent on nitrite and mitochondrial electron transport rather than on arginine or nitrate. Overall, these results indicate that NOS, NR and a mitochondrial-dependent nitrite-reducing activity cooperate to produce Å NO during A. thaliana-P. syringae interaction.

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“…However, there is evidence that biological NOderived oxidants such as nitrogen dioxide and carbonate radical anion dioxide promote cell injury (28)(29)(30). These events depend on the intracellular concentration of low-molecular weight thiols such as glutathione (24,31,32).…”

Section: Growth Of Leishmania Donovani Clonesmentioning

confidence: 99%

Glutathione and the redox control system trypanothione/trypanothione reductase are involved in the protection of Leishmania spp. against nitrosothiol-induced cytotoxicity

Romão

Tovar

Fonseca

et al. 2006

Braz J Med Biol Res

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Glutathione is the major intracellular antioxidant thiol protecting mammalian cells against oxidative stress induced by oxygen-and nitrogen-derived reactive species. In trypanosomes and leishmanias, trypanothione plays a central role in parasite protection against mammalian host defence systems by recycling trypanothione disulphide by the enzyme trypanothione reductase. Although Kinetoplastida parasites lack glutathione reductase, they maintain significant levels of glutathione. The aim of this study was to use Leishmania donovani trypanothione reductase gene mutant clones and different Leishmania species to examine the role of these two individual thiol systems in the protection mechanism against S-nitroso-N-acetyl-D,L-penicillamine (SNAP), a nitrogen-derived reactive species donor. We found that the resistance to SNAP of different species of Leishmania was inversely correlated with their glutathione concentration but not with their total low-molecular weight thiol content (about 0.18 nmol/10 7 parasites, regardless Leishmania species). The glutathione concentration in L. amazonensis, L. donovani, L. major, and L. braziliensis were 0.12, 0.10, 0.08, and 0.04 nmol/10 7 parasites, respectively. L. amazonensis, that have a higher level of glutathione, were less susceptible to SNAP (30 and 100 µM). The IC 50 values of SNAP determined to L. amazonensis, L. donovani, L. major, and L. braziliensis were 207.8, 188.5, 160.9, and 83 µM, respectively. We also observed that L. donovani mutants carrying only one trypanothione reductase allele had a decreased capacity to survive (~40%) in the presence of SNAP (30-150 µM). In conclusion, the present data suggest that both antioxidant systems, glutathione and trypanothione/trypanothione reductase, participate in protection of Leishmania against the toxic effect of nitrogen-derived reactive species.

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Role of peroxynitrite in macrophage microbicidal mechanisms in vivo revealed by protein nitration and hydroxylation

Cited by 112 publications

References 45 publications

Protein 3-nitrotyrosine formation during Trypanosoma cruzi infection in mice

Protein 3-nitrotyrosine formation during Trypanosoma cruzi infection in mice

Nitrite as the major source of nitric oxide production by Arabidopsis thaliana in response to Pseudomonas syringae

Glutathione and the redox control system trypanothione/trypanothione reductase are involved in the protection of Leishmania spp. against nitrosothiol-induced cytotoxicity

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