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The role of docosahexaenoic acid in mediating mitochondrial membrane lipid oxidation and apoptosis in colonocytes.
- Source :
-
Carcinogenesis [Carcinogenesis] 2005 Nov; Vol. 26 (11), pp. 1914-21. Date of Electronic Publication: 2005 Jun 23. - Publication Year :
- 2005
-
Abstract
- Docosahexaenoic acid (DHA, 22:6 n-3) from fish oil, and butyrate, a fiber fermentation product, work coordinately to protect against colon tumorigenesis in part by inducing apoptosis. We have recently demonstrated that dietary DHA is incorporated into mitochondrial membrane phospholipids, thereby enhancing oxidative stress induced by butyrate metabolism. In order to elucidate the subcellular origin of oxidation induced by DHA and butyrate, immortalized young adult mouse colonocytes were treated with 0-200 microM DHA or linoleic acid (LA, 18:2 n-6; control) for 72 h with or without 5 mM butyrate for the final 24 h. Cytosolic reactive oxygen species, membrane lipid oxidation, and mitochondrial membrane potential (MP), were measured by live-cell fluorescence microscopy. After 24 h of butyrate treatment, DHA primed cells exhibited a 151% increase in lipid oxidation (P < 0.01), compared with no butyrate treatment, which could be blocked by a mitochondria-specific antioxidant, 10-(6'-ubiquinoyl) decyltriphenylphosphonium bromide (MitoQ) (P < 0.05). Butyrate treatment of LA pretreated cells did not show any significant effect. In the absence of butyrate, DHA treatment, compared with LA, increased resting MP by 120% (P < 0.01). In addition, butyrate-induced mitochondrial membrane potential (MP), dissipation was 21% greater in DHA primed cells as compared with LA at 6 h. This effect was reversed by preincubation with inhibitors of the mitochondrial permeability transition pore, cyclosporin A or bongkrekic acid (1 microM). The functional importance of these events is supported by the demonstration that DHA and butyrate-induced apoptosis is blocked by MitoQ. These data indicate that DHA and butyrate potentiate mitochondrial lipid oxidation and the dissipation of MP which contribute to the induction of apoptosis.
- Subjects :
- Animals
Anti-Bacterial Agents pharmacology
Antioxidants pharmacology
Bongkrekic Acid pharmacology
Butyrates pharmacology
Cells, Cultured
Colon cytology
Colon metabolism
Cyclosporine pharmacology
Epithelial Cells cytology
Epithelial Cells drug effects
Epithelial Cells metabolism
Immunosuppressive Agents pharmacology
Linoleic Acid pharmacology
Mice
Microscopy, Fluorescence
Mitochondria metabolism
Organophosphorus Compounds pharmacology
Oxidative Stress
Ubiquinone analogs & derivatives
Ubiquinone pharmacology
Apoptosis drug effects
Colon drug effects
Docosahexaenoic Acids pharmacology
Lipid Peroxidation drug effects
Membrane Potentials drug effects
Mitochondria drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0143-3334
- Volume :
- 26
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Carcinogenesis
- Publication Type :
- Academic Journal
- Accession number :
- 15975958
- Full Text :
- https://doi.org/10.1093/carcin/bgi163