1-Methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (
salsolinol), an endogenous
neurotoxin present in the mammalian brain, is known to perform a role in the pathogenesis of
Parkinson's disease. In this study, we evaluated oxidative modifications of
ferritin occurring after incubation with
salsolinol. When
ferritin was incubated with
salsolinol,
protein aggregation increased in a time-dependent manner.
Free radical scavengers inhibited this
salsolinol-mediated
ferritin modification. The exposure of
ferritin to
salsolinol also results in the generation of
protein carbonyl compounds and the formation of
dityrosine. The results of this study show that
free radicals may perform a pivotal role in
salsolinol-mediated
ferritin modification.
Histidine dipeptides, such as
carnosine, have been proposed to function as
antioxidant agents in vivo. In this study, we also attempted to determine whether the
histidine dipeptides,
carnosine and N-acetyl-
carnosine, could prevent
salsolinol-mediated oxidative modification of
ferritin. Our results showed that both
carnosine and N-acetyl-
carnosine significantly reduced
ferritin aggregation. Both compounds effectively inhibited the formation of both carbonyl compounds and
dityrosine. These results suggest that
carnosine derivatives can, indeed, protect against
salsolinol-mediated
ferritin modification, as the consequence of
free radical-scavenging activity.