Serum concentrations of nitrite in patients with HIV-1 infection.

Abstract

Aims-To measure circulating concentrations of nitrite in patients with HIV-1 infection. Methods-Nitrite concentrations were measured using the Griess reaction adapted to microtitre plates in the serum of 10 asymptomatic HIV-1 positive patients, 33 patients with AIDS with cerebral disorders, 17 patients with AIDS with pulmonary involvement, and in eight patients with AIDS with other disorders. Nitrite concentrations were also measured in bronchoalveolar lavage (BAL) fluid and cerebrospinal fluid (CSF) of patients with AIDS with pulmonary involvement and cerebral disorders, respectively. Results-Increased serum concentrations of nitrite were observed in patients with pulmonary involvement, and in particular in serum and in BAL samples of patients with interstitial pneumonia (36.2 (26.2) ,tmoMl and 0.3 (0.4) pmol/l, respectively).Increased serum concentrations of nitrite were also noted in patients with retinitis caused by infection with cytomegalovirus. Serum nitrite concentrations were also raised in patients with cerebral toxoplasmosis, whereas normal serum concentrations were found in patients with HIV-1 encephalopathy and cryptococcal meningitis. Nitrite concentrations in CSF were not raised in patients with cerebral disorders. Conclusions-These results suggest that production of nitrite in patients with AIDS with concomitant opportunistic infections may be part of the host defense against opportunistic organisms.

Mechanism of Reaction of Myeloperoxidase with Nitrite

“…This is one of the most intriguing developments in the biochemistry of MPO, 1 because nitration of tyrosine residues in proteins occurs in a wide range of inflammatory diseases involving activated neutrophils and macrophages. Since nitrite is observed to accumulate upon nitric oxide synthase activation in many inflammatory diseases (7) and nitrite concentrations can be locally higher in tissues than those measured in plasma (8,9), nitration mediated by MPO could be an additional defense function.…”

Lack of Tyrosine Nitration by Hypochlorous Acid in the Presence of Physiological Concentrations of Nitrite

“…Typically, levels of NO 2 Ϫ found in plasma taken from healthy human volunteers range between 0.5 and 21.0 M (5, 6), and levels are significantly elevated during inflammation, e.g. up to 36 M in patients with human immunodeficiency virus infection (7). Serum NO 2 Ϫ levels in patients with rheumatoid arthritis (8), systemic sclerosis (9), and systemic lupus erythematosus (10) are reported to be in the millimolar range, whereas in the synovial fluid of patients with rheumatoid arthritis NO 2 Ϫ levels are reported to range from 0.3 to 15 M (11-13).…”

Protein self‐modification by heme‐generated reactive species

“…(14) Mb is a good target for the investigation of the capability of the reactive species generated by catechols of modifying aminoacid residues of the heme protein that generated them. In particular, HMb contains 20 Lys (residues 17,35,43,46,48,51,57,63,64,78,79,80,88,97,99,103,119,134,141, and 148), 9 His (residues 24,36,48,64,81,82,93,97, and 119) and a single Cys (110). Although the three-dimensional structure of HMb has not been resolved yet, most probably the amino-acid disposition does not differ significantly from that of the HMb mutant Ala110Cys, the structure of which is known (114).…”

“…Moreover, the target of these reactions could be the endogenous Tyr and Cys residues of the proteins. The physiological relevance of these reactions raises from several aspects: (i) the presence of nitrated proteins is often observed in pathophysiological conditions (33,(69)(70)(71); (ii) the search of the biochemical pathways responsible for biological nitration and the identification of specific protein targets for nitration is essential for the understanding of the mechanisms of NO-derived pathologies (72); (iii) during inflammatory diseases, the levels of H 2 O 2 and NO 2 2 markedly increase (57,58,60,73); and (iv) both Mb and Hb are present in large amount in the body (5,12), so that even the low efficiency exhibited by their reactions, compared with peroxidases, could be of physiological relevance; Ngb is present in low concentration in the brain but reaches $100 lM in retinal cells (74,75 close to the levels that can be reached in vivo under conditions of oxidative stress) were analyzed by HPLC-ESI-MS/MS. The main targets of the oxidizing and nitrating species are the heme prosthetic group and the Tyr and Cys residues.…”