Hydroxyl radical is produced via the Fenton reaction in submitochondrial particles under oxidative stress: implications for diseases associated with iron accumulation
| Autor: | David P. Cox, Melissa M. Mackey, Amy A. Diaz, Carin Thomas |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Antioxidant
Physiology medicine.medical_treatment Clinical Biochemistry Submitochondrial Particles Catechols Oxidative phosphorylation medicine.disease_cause Biochemistry Mitochondria Heart chemistry.chemical_compound medicine Hydroxybenzoates Animals Submitochondrial particle Heart metabolism Chromatography High Pressure Liquid chemistry.chemical_classification Reactive oxygen species biology Hydroxyl Radical Biochemistry (medical) Cell Biology Oxidative Stress chemistry Catalase biology.protein Hydroxyl radical Cattle Reactive Oxygen Species Oxidative stress |
| Zdroj: | Redox report : communications in free radical research. 14(3) |
| ISSN: | 1743-2928 |
| Popis: | Mitochondrial dysfunction and reactive oxygen species (ROS) are often implicated in diseases involving oxidative stress and elevated iron. As mitochondria produce ATP by oxidative phosphorylation, ROS by-products are generated from the electron transport chain. Although superoxide and hydrogen peroxide have been thoroughly investigated, little evidence documents hydroxyl radical (HO(*)) production in mitochondria. In order to determine whether HO(*) is generated under oxidative stress conditions by a Fenton-type mechanism, bovine heart submitochondrial particles were examined for HO(*) in the presence and absence of iron ligands, antioxidant enzymes and HO(*) scavengers. HO(*) was measured as 2,3- and 2,5-dihydroxybenzoic acid (DHBA), using HPLC with electrochemical detection. The iron ligand desferrioxamine significantly decreased DHBAs, indicating that HO(*) generation required iron redox-cycling. In addition, results from exogenous SOD and catalase, exogenous hydrogen peroxide, and HO(*)-scavenger studies support a Fenton-type reaction mechanism. The results indicate that increased HO(*) levels occur in mitochondria under oxidative stress and that the HO(*) levels can be modulated with antioxidant enzymes and iron ligands. Our findings together with reports on iron accumulation in degenerative diseases highlight the importance of developing mitochondrial-targeted antioxidants for the therapeutic intervention of diseases associated with mitochondrial dysfunction and oxidative stress. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|