Monoamine and iron-related toxicity: from "serotonin-binding proteins" to lipid peroxidation and apoptosis in PC12 cells.
1. Monoamines do not form coordination bonds with a preformed iron-serotonin-binding protein (SBP) complex, as initially believed. Instead, metals oxidize the monoamines either directly (manganese, copper) or by oxygen free radical formation (iron), the oxidation products bind covalently to SBP and the conjugates are able to undergo redox cycling. These interactions are denoted as a "molecular oxidative mechanism." 2. Dopamine in combination with iron induces lipid peroxidation and apoptosis in PC12 cells by a stress oxidative-Ca2+ independent mechanism. 3. Dopamine-iron cytotoxicity may have relevance to an understanding of the mechanism by which dopaminergic neurons are eroded in some neurodegenerative disorders.
Velez-Pardo
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C
Department of Protein Chemistry, Free University Brussels, Belgium.
Del Rio
M J
MJ
Ebinger
G
G
Vauquelin
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G
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015306:Biogenic Monoamines / Q000378:metabolism*; D002457:Cell Extracts / Q000494:pharmacology; D005609:Free Radicals; D007501:Iron / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology*; D016716:PC12 Cells; D051381:Rats; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism
D015306:Biogenic Monoamines; D002457:Cell Extracts; D005609:Free Radicals; D011985:Receptors, Serotonin; D012701:Serotonin; D007501:Iron