Neurodegenerative disorders: the role of peroxynitrite.

Inflammatory reaction is thought to be an important contributor to neuronal damage in neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and the parkinsonism dementia complex of Guam. Among the toxic agents released in brain tissues by activated cells, we focus attention in this review on peroxynitrite, the product of the reaction between nitric oxide (NO) and superoxide. Peroxynitrite is a strong oxidizing and nitrating agent which can react with all classes of biomolecules.

Potential role of the peroxidase-dependent metabolism of serotonin in lowering the polymorphonuclear leukocyte bactericidal function.

Serotonin (5-hydroxytryptamine, 5-HT) significantly and dose-dependently suppressed the luminol-enhanced chemiluminescence (CL) signal generated by polymorphonuclear leukocytes (PMN) activated with phorbol myristate acetate (PMA), but did not modify either lucigenin-enhanced CL or the reduction of superoxide dismutase-inhibitable cytochrome c. Moreover, stimulation of PMNs previously incubated with 5-HT resulted in a threefold increase in 5-HT equivalents bound to the proteins of PMN. The addition of catalase or sodium azide substantially reduced this binding.

Nitration of tyrosyl-residues from extra- and intracellular proteins in human whole blood.

We measured the amounts of tyrosine and 3-nitrotyrosine (NO2-tyrosine) in proteins of plasma and polymorphonuclear leukocytes (PMN) from human whole blood before and after activation with phorbol ester (PMA) or calcium ionophore (A 23187). In unstimulated blood, no significant nitration of tyrosine was detected into PMN proteins, but a NO2-tyrosine/tyrosine ratio of 0.7% was detected in plasma proteins.

Neutrophil-catalysed dimerisation of tyrosyl peptides.

Evidence is given that tyrosyl-peptides are dimerised by polymorphonuclear leukocytes leading to a new family of compounds. The products formed are homo- and hetero-dimeric peptides with linkage between the tyrosyl residues. This corresponds to a dityrosine structure as determined by analytic and spectroscopic data.