6-Hydroxydopamine releases iron from ferritin and promotes ferritin-dependent lipid peroxidation
Abstract
Iron was released from ferritin by the catecholamine analog, 6-hydroxydopamine. Iron release was more efficient under nitrogen than in air, suggesting that the hydroquinone has the major role in the process. Superoxide dismutase, alone or in combination with catalase, strongly inhibited 6-hydroxydopamine oxidation and greatly enhanced the amount of ferritin iron release. Catalase alone had a similar, but lesser effect. Iron released from ferritin accelerated the autoxidation of 6-hydroxydopamine. This occurred by a mechanism that was inhibited by a combination of catalase and a chelator, and to a lesser extent by superoxide dismutase. 6-Hydroxydopamine was a good promoter of metal-catalysed lipid peroxidation, and ferritin-iron participated in the process. Superoxide dismutase, and to a lesser extent catalase, stimulated peroxidation catalysed by adventitious levels of iron, but in the presence of ferritin, each enzyme was inhibitory. It appears that the greatly enhanced iron release seen under these conditions accelerated the autoxidation of 6-hydroxydopamine so that less was available to participate in peroxidative reactions. However, when 6-hydroxydopamine autoxidation was prevented by a combination of superoxide dismutase and catalase, lipid peroxidation was also inhibited, suggesting that some intermediate of autoxidation is a further requirement for the process.
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Neurotoxic 6-hydroxydopamine and superoxide radical are able to release free iron from ferritin, which may participate in Fenton chemistry, forming ROS and initiating lipid peroxidation.
“It has been declared, that neurotoxic 6-hydroxydopamine (and also superoxide radical) is able to release “free iron” from ferritin which in turn may participate in Fenton chemistry, forming ROS and initiating lipid peroxidation (Monteiro and Winterbourn 1989).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Monteiro and Winterbourn 1989
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- Authors
- Monteiro, H. P., & Winterbourn, C. C.
- Affiliations
- Christchurch Hospital (NZ)
- Corresponding author
- Winterbourn, Christine C.
- Venue
- Biochemical Pharmacology
- Publisher
- Elsevier BV
- Published
- 1989-12
- Volume
- 38
- Issue
- 23
- Pages
- 4177-4182
- ISSN
- 0006-2952 (ISSN-L)
- OpenAlex
- W2063707367
- Cited by
- 125
- References
- 27
- Citations by year
- 2025: 4 · 2023: 2 · 2021: 1 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 2 · 2013: 5 · 2012: 2
- FWCI
- 2.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Topics
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Keywords
- 6-hydroxydopamine, ferritin, iron release, lipid peroxidation, autoxidation, superoxide dismutase, catalase, hydroquinone, metal-catalyzed oxidation, catecholamine analogs, iron chelation
- MeSH terms
- Catalase, Ferritins, Free Radicals, Hydroxydopamines, Iron, Lipid Peroxides, Nitrogen, Oxidation-Reduction, Superoxide Dismutase, Oxidopamine
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