Nitrosation of melatonin by nitric oxide and peroxynitrite

Abstract

Peroxynitrite (ONOO − ) is an endogenous molecule, formed by rapid coupling between NO and O 2 − . ONOO − is known to be a strong oxidant of thiols and metalloorganic compounds and also a nitrating agent of aromatic compounds such as tyrosine. However, its chemistry is not yet well elucidated under physiological conditions. Melatonin, which is an indole‐amine produced by the pineal gland and other organs, has antioxidant properties. We show that melatonin reacts with ONOO − in phosphate‐buffered solutions. We provide evidence of nitrosation and oxidation at the pyrrole nitrogen leading to 1‐nitrosomelatonin and 1‐hydroxymelatonin, these being the major reactions in aqueous phosphate‐buffered solutions besides other aromatic hydroxylations and nitration. 4‐Nitromelatonin is formed, but in small amounts. The kinetics of all transformations were strictly dependent on ONOO − decay, whereas yields varied with pH and the presence of CO 2 . The N‐oxidation became competitive with nitrosation at pH 7.4, in medium containing a sufficient amount of CO 2 . A proposed mechanism involves the transient formation of melatonyl radical and ONOO radical derived from ONOO − decay.