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

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Title: The role of docosahexaenoic acid in mediating mitochondrial membrane lipid peroxidation and apoptosis in colonocytes.
Author: Ng, Yee Voon
Abstract: Colon cancer is the second leading cause of cancer death in the United States . Epidemiological data indicate that the consumption of dietary fiber and fish /marine products favorably modulate colon tumorigenesis . Docosahexaenoic acid (DHA , 22 :6n -3 ) from fish oil , and butyrate , a fiber fermentation product generated in colon , protect against colon tumorigenesis in part by inducing apoptosis . We have shown that DHA is incorporated into mitochondrial membrane phospholipids , which enhances oxidative stress and mitochondrial membrane potential (MP ) dissipation . To elucidate the subcellular origin of oxidation induced by DHA and butyrate exposure , young adult mouse colonocytes (YAMC ) were treated with 0200 ? ?M DHA , linoleic acid (LA , 18 :2n -6 ) or no fatty acid (control ) for 72 h with or without 5 mM butyrate for the final 6 -24 h . Real time analysis of cellular membrane lipid oxidation , as indicated by oxidation of a lipophilic vital dye , mitochondrial permeability transition (MPT ) , as characterized by MP dissipation , and cytosolic ROS production , as depicted by hydrophilic ROS reactive fluorophore accumulation , were measured by living cell fluorescence microscopy . After 24 h of butyrate treatment , DHA primed cells showed a 29 % increase in lipid oxidation (p <0 .01 ) , compared to no butyrate treatment , which could be blocked by a mitochondria targeted antioxidant , MitoQ (p <0 .05 ) , whereas LA treatment did not show an effect . In the absence of butyrate , DHA treatment , compared to LA , increased resting MP by 14 % (p <0 .01 ) . In addition , butyrate -induced MP dissipation was greater (20 % ) in DHA primed cells as compared to LA (10 % ) . This effect was blocked by pre -incubation with MPT inhibitors , cyclosporin A or bongkrekic acid at 1 ? ?M . These data suggest an increase in mitochondrial lipid oxidation and the resultant change in MP may contribute to the induction of apoptosis by DHA with butyrate as shown previously .
URI: http : / /hdl .handle .net /1969 .1 /2676
Date: 2005-11-01

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The role of docosahexaenoic acid in mediating mitochondrial membrane lipid peroxidation and apoptosis in colonocytes.. Available electronically from http : / /hdl .handle .net /1969 .1 /2676 .

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