RT Journal Article
T1 Autoxidation and MAO-mediated metabolism of dopamine as a potential cause of oxidative stress: role of ferrous and ferric ions
A1 Hermida Ameijeiras, Álvaro
A1 Méndez Álvarez, Estefanía
A1 Sánchez Iglesias, Sofía
A1 Sanmartín Suárez, Carolina
A1 Soto-Otero, Ramón
K1 Dopamine autoxidation
K1 Dopamine metabolism
K1 Hydroxyl radical
K1 Lipid peroxidation
K1 Protein oxidation
K1 Mitochondrial preparations
K1 Parkinson’s disease
AB The autoxidation and monoamine oxidase (MAO)-mediated metabolism of dopamine (3-hydroxytyramine; DA) cause a continuous production of hydroxyl radical (radical dotOH), which is further enhanced by the presence of iron (ferrous iron, Fe2+ and ferric ion, Fe3+). The accumulation of hydrogen peroxide (H2O2) in the presence of Fe2+ appears to discard the involvement of the Fenton reaction in this process. It has been found that the presence of DA significantly reduces the formation of thiobarbituric acid reagent substances (TBARS), which under physiological conditions takes place in mitochondrial preparations. The presence of DA is also able to reduce TBARS formation in mitochondrial preparations even in the presence of iron (Fe2+ and Fe3+). However, DA boosted the carbonyl content of mitochondrial proteins, which was further increased in the presence of iron (Fe2+ and Fe3+). This latter effect is also accompanied by a significant reduction in thiol content of mitochondrial proteins. It has also been observed how the pre-incubation of mitochondria with pargyline, an acetylenic MAO inhibitor, reduces the production of radical dotOH and increases the formation of TBARS. Although, the MAO-mediated metabolism of DA increases MAO-B activity, the presence of iron inhibits both MAO-A and MAO-B activities. Consequently, DA has been shown to be a double-edged sword, because it displays antioxidant properties in relation to both the Fenton reaction and lipid peroxidation and exhibits pro-oxidant properties by causing both generation radical dotOH and oxidation of mitochondrial proteins. Evidently, these pro-oxidant properties of DA help explain the long-term side effects derived from l-DOPA treatment of Parkinson’s disease and its exacerbation by the concomitant use of DA metabolism inhibitors.
PB Elsevier
SN 0197-0186
YR 2004
FD 2004
LK http://hdl.handle.net/10347/32530
UL http://hdl.handle.net/10347/32530
LA eng
NO Neurochemistry International, Volume 45, Issue 1, 2004, Pages 103-116
NO This study was supported by Grant BFI2003-00493 from the Ministerio de Ciencia y Tecnologı́a, Madrid (Spain).
DS Minerva
RD 28 abr 2026