The role of docosahexaenoic acid in mediating mitochondrial membrane lipid oxidation and apoptosis in colonocytes

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 en...

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Bibliographic Details
Published in:	Carcinogenesis (New York) Vol. 26; no. 11; pp. 1914 - 1921
Main Authors:	Ng, Yeevoon, Barhoumi, Rola, Tjalkens, Ronald B., Fan, Yang-Yi, Kolar, Satya, Wang, Naisyin, Lupton, Joanne R., Chapkin, Robert S.
Format:	Journal Article
Language:	English
Published:	Oxford Oxford University Press 01-11-2005 Oxford Publishing Limited (England)
Subjects:	10-(6′-ubiquinoyl) decyltriphenylphosphonium bromide alpha-tocopherol Animals Anti-Bacterial Agents - pharmacology Antioxidants - pharmacology Apoptosis - drug effects Biological and medical sciences BKA bongkrekic acid Bongkrekic Acid - pharmacology Butyrates - pharmacology Carcinogenesis, carcinogens and anticarcinogens Cells, Cultured Colon - cytology Colon - drug effects Colon - metabolism CSA cumene hydroperoxide CumOOH Cyclosporine - pharmacology cyclosporine A DHA diphenyl-1-pyrenylphosphine docosahexaenoic acid Docosahexaenoic Acids - pharmacology DPPP eicosapentaenoic acid ELISA enzyme-linked immunosorbent assay EPA Epithelial Cells - cytology Epithelial Cells - drug effects Epithelial Cells - metabolism Immunosuppressive Agents - pharmacology lactate dehydrogenase LDH linoleic acid Linoleic Acid - pharmacology Lipid Peroxidation - drug effects Medical sciences Membrane Potentials - drug effects Mice Microscopy, Fluorescence Mitochondria - drug effects Mitochondria - metabolism mitochondrial membrane potential mitochondrial permeability transition MitoQ MPT Organophosphorus Compounds - pharmacology Oxidative Stress polyunsaturated fatty acids PUFA reactive oxygen species ROS Tumors Ubiquinone - analogs & derivatives Ubiquinone - pharmacology YAMC young adult mouse colonocyte α-TOC Mitochondria Cell death Polyunsaturated fatty acid Lipids Membrane Oxidation Docosahexaenoic acid Apoptosis
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Summary:	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 μM 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 μM). 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.
Bibliography:	istex:052DD8BB93B5CFF2A4ECE615CA4C7336BC3542AC To whom correspondence should be addressed. Tel: +979 845 0448; Fax: +979 862 2662; Email: r-chapkin@tamu.edu local:bgi163 ark:/67375/HXZ-PBHQ9M9M-B ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0143-3334 1460-2180
DOI:	10.1093/carcin/bgi163