N-tert-butyl hydroxylamine, a mitochondrial antioxidant, protects human retinal pigment epithelial cells from iron overload: relevance to macular degeneration.
Age-related macular degeneration (AMD) is the leading cause of severe visual impairment in the elderly in developed countries. AMD patients have elevated levels of iron within the retinal pigment epithelia (RPE), which may lead to oxidative damage to mitochondria, disruption of retinal metabolism, and vision impairment or loss. As a possible model for iron-induced AMD, we investigated the effects of excess iron in cultured human fetal RPE cells on oxidant levels and mitochondrial cytochrome c oxidase (complex IV) function and tested for protection by N-tert-butyl hydroxylamine (NtBHA), a known mitochondrial antioxidant. RPE exposure to ferric ammonium citrate resulted in a time- and dose-dependent increase in intracellular iron, which increased oxidant production and decreased glutathione (GSH) levels and mitochondrial complex IV activity. NtBHA addition to iron-overloaded RPE cells led to a reduction of intracellular iron content, oxidative stress, and partial restoration of complex IV activity and GSH content. NtBHA might be useful in AMD due to its potential to reduce oxidative stress, mitochondrial damage, and age-related iron accumulation, which may damage normal RPE function and lead to loss of vision.
Children's Hospital Oakland Research Institute, Nutrition and Metabolism Center, 5700 Martin Luther King Jr. Way, Oakland, CA 94609-1673, USA.
Ludmila A
LA
Voloboueva
David W
DW
Killilea
Hani
H
Atamna
Bruce N
BN
Ames
D000368:Aged; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans; D006898:Hydroxylamines / Q000378:metabolism / Q000494:pharmacology*; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000378:metabolism / Q000494:pharmacology; D019190:Iron Overload / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D008268:Macular Degeneration / Q000188:drug therapy* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010857:Pigment Epithelium of Eye / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000975:Antioxidants; D006898:Hydroxylamines; D007502:Iron Chelating Agents; C072771:N-tert-butylhydroxylamine; D007501:Iron