Contrasting effects of catecholic and O-methylated tetrahydroisoquinolines on hydroxyl radical production.
Tetrahydroisoquinolines (TIQs) are intraneuronal, catecholamine-derived alkaloids that have been implicated in the etiology of Parkinson's disease and in alcohol related disorders. The in vitro production of the cytotoxic hydroxyl radical (*OH) was recorded during the autoxidation of salsolinol (SAL) and salsolinol-1-carboxylic acid (SAL-1C), but not when these two catecholic TIQs were oxidized by tyrosinase. Significantly higher levels of the radical were produced when these catecholic TIQs were incubated with *OH generating complexes, or with chelated iron. In contrast, mono-O-methylated TIQs such as salsoline (SLN) and salsoline-1-carboxylic acid (SLN-1C) did not generate *OH during autoxidation or when incubated with chelated iron or tyrosinase. Radical production by *OH-generating complexes was reduced in the presence of O-methylated TIQs. The neurotoxicity of TIQs may result from their propensity to autoxidize and generate reactive quinoids and ensuing oxygen radicals. The functional significance of the replacement of a hydroxyl group attached to C-7 of SAL or SAL-1C with a methoxyl group remains to be determined. This single structural modification may prevent mono-O-methylated TIQs from participating in catalytic redox cycling reactions that would otherwise augment *OH production. If true, then O-methylation and other cellular mechanisms that circumvent the autoxidation of catecholamine-derived TIQs may reduce the likelihood of these substances forming cytotoxic quinoids and influencing endogenous *OH-generating reactions.
Nappi
A J
AJ
Department of Biology, Loyola University Chicago, Chicago, IL 60626, USA. anappi@orion.it.luc.edu
Vass
E
E
Collins
M A
MA
D002396:Catechols / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D017665:Hydroxyl Radical / Q000737:chemistry*; D007546:Isoquinolines / Q000737:chemistry*; D010084:Oxidation-Reduction; D044005:Tetrahydroisoquinolines
D002396:Catechols; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D017665:Hydroxyl Radical; C050386:1-methyl-1,2,3,4-tetrahydroisoquinoline