Nitric oxide-induced oxidation of 5,6-dihydroxyindole and 5,6-dihydroxyindole-2-carboxylic acid under aerobic conditions: non-enzymatic route to melanin pigments of potential relevance to skin (photo)protection.
Diffusible melanin-related metabolites have recently been suggested to subserve a variety of functions that are critical for protection of skin against inflammatory stimuli and oxidative tissue injury. We report here the results of in vitro studies showing that 5,6-dihydroxyindole (DHI) and its 2-carboxylic acid (DHICA) exhibit a marked reactivity toward potentially cytotoxic nitrogen oxides produced by autoxidation of nitric oxide (NO) under physiologically relevant conditions. Exposure of DHI or DHICA to NO in air-equilibrated 0.1 M phosphate buffer, pH 7.4, resulted in a fast, concentration-dependent consumption of the substrates and the concomitant deposition of dark melanin-like pigments. All NO-induced oxidations were completely inhibited in the absence of oxygen. Addition of 10 microM DHI and DHICA completely prevented the oxidation of 10 microM alpha-tocopherol in 0.1 M phosphate buffer, pH 7.4 in the presence of 300 microM NO. Overall, these results shed light on novel oxidative pathways of melanin-related metabolites of possible relevance to the mechanisms of skin hyperpigmentation under oxidative stress conditions.
Novellino
L
L
Department of Organic and Biological Chemistry, University of Naples Federico II, Italy.
d'Ischia
M
M
Prota
G
G
D000332:Aerobiosis; D000818:Animals; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000737:chemistry / Q000378:metabolism*; D008543:Melanins / Q000737:chemistry / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D012880:Skin Pigmentation / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects; D014810:Vitamin E / Q000737:chemistry / Q000378:metabolism
D007211:Indoles; D008543:Melanins; D014810:Vitamin E; D009569:Nitric Oxide; C030692:5,6-dihydroxy-2-indolylcarboxylic acid; C033871:5,6-dihydroxyindole