dc.contributor.author | Mayo Barrallo, Juan Carlos | |
dc.contributor.author | Sainz Menéndez, Rosa María | |
dc.contributor.author | Tan, Dun-Xian | |
dc.contributor.author | Hardeland, Rüdiger | |
dc.contributor.author | Leon, Josefa | |
dc.contributor.author | Rodríguez Sánchez, María del Carmen | |
dc.contributor.author | Reiter, Russel J. | |
dc.date.accessioned | 2024-03-20T08:53:43Z | |
dc.date.available | 2024-03-20T08:53:43Z | |
dc.date.issued | 2005 | |
dc.identifier.uri | https://hdl.handle.net/10651/72012 | |
dc.description.abstract | nflammation is a complex phenomenon involving multiple cellular and molecular interactions which must be tightly regulated. Cyclooxygenase-2 (COX) is the key enzyme that catalyzes the two sequential steps in the biosynthesis of PGs from arachidonic acid. The inducible isoform of COX, namely COX-2, plays a critical role in the inflammatory response and its over-expression has been associated with several pathologies including neurodegenerative diseases and cancer. Melatonin is the main product of the pineal gland with well documented antioxidant and immuno-modulatory effects. Since the action of the indole on COX-2 has not been previously described, the goal of the present report was to test the effect of melatonin on the activities of COX-2 and inducible nitric oxide synthase (iNOS), using lipopolysaccharide (LPS)-activated RAW 264.7 macrophages as a model. Melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), prevented COX-2 activation induced by LPS, without affecting COX-1 protein levels. The structurally related compound 6-methoxy-melatonin only partially prevented the increase in COX-2 protein levels induced by the toxin. Likewise melatonin prevented iNOS activation and reduced the concentration of products from both enzymes, PGE2 and nitric oxide. Another endogenous antioxidant like N-acetyl-cysteine (NAC) did not reduced COX-2 significantly. The current finding corroborates a role of melatonin as an anti-inflammatory agent and, for the first time, COX-2 and iNOS as molecular targets for either melatonin or its metabolites AFMK and AMK. These anti-inflammatory actions seem not to be exclusively mediated by the free radical scavenging properties of melatonin. As a consequence, the present work suggests these substances as a new class of potential anti-inflammatory agents without the classical side effects due to COX-1 inhibition. | spa |
dc.language.iso | eng | spa |
dc.relation.ispartof | Journal of Neuroimmunology, 165(1-2) | spa |
dc.rights | CC Reconocimiento – No Comercial – Sin Obra Derivada 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Melatonin | spa |
dc.subject | AFMK | |
dc.subject | AMK | |
dc.subject | COX-2 | |
dc.subject | INOS | |
dc.subject | Raw 264.7 macrophage | |
dc.subject | LPS | |
dc.title | Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophages. | spa |
dc.type | journal article | spa |
dc.identifier.doi | 10.1016/j.jneuroim.2005.05.002 | |
dc.relation.publisherversion | https://doi.org/10.1016/j.jneuroim.2005.05.002 | |
dc.rights.accessRights | open access | spa |
dc.type.hasVersion | SMUR | spa |