Conjugated linoleic acid isomers' roles in the regulation of PPARγ and NF-κB DNA binding and subsequent expression of antioxidant enzymes in human umbilical vein endothelial cells

Department of Nutrition and Environmental Sciences, University of Nevada, Reno, USA.
Nutrition (Impact Factor: 2.93). 04/2009; 25(7-8):800-11. DOI: 10.1016/j.nut.2009.01.003
Source: PubMed


Conjugated linoleic acid (CLA) isomers have shown health benefits. Because CLA isomers may act as activators for peroxisome proliferator-activated receptors and may induce antioxidant enzymes, this study was conducted to examine the effects of CLA isomers on the gene expression of antioxidant enzymes, copper/zinc superoxide dismutase, and catalase in human umbilical vein endothelial cells.
Human umbilical vein endothelial cells were treated with graded concentrations of the 9-cis, 11-trans or the 10-trans, 12-cis-CLA isomer for 24 h.
The 9-cis, 11-trans-CLA treatments resulted in increases in transcription factor DNA binding activities and expression of antioxidant enzymes at 0-25 micromol/L and an increase in lipid peroxidation only at the lowest concentrations (5 micromol/L). The 10-trans, 12-cis-CLA treatments resulted in increases in transcription factor DNA binding activities at 0-25 micromol/L and highest levels of mRNA of both antioxidant enzymes, superoxide dismutase protein, and lipid peroxidation only at the lowest concentrations (5 micromol/L). The 9-cis, 11-trans-CLA treatments produced expression of antioxidant enzymes, except catalase protein, that were positively correlated with lipid peroxidation. Positive correlations were found between expression of antioxidant enzymes, except catalase protein, and lipid peroxidation for 10-trans, 12-cis-CLA treatments. Although CLA isomers exhibit mostly stimulatory effects in expression of antioxidant enzymes, interestingly, the lowest concentrations of both CLA isomers resulted in increases in thiobarbituric acid-reactive substance levels.
An understanding of the optimal concentrations of CLA isomers, which stimulate the benefits of antioxidant enzyme induction, may require careful CLA titration to determine predictable and dependable therapeutic strategies against adverse effects, such as pro-oxidants.

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    • "Very recent studies on PPARγ-DNA binding activity in human umbilical vein endothelial cells after treatment with the individual CLA isomers showed that the concentration determines whether CLA isomers exert inhibitory or a stimulatory effects in inflammatory and atherogenic processes, and that microenvironments also influence CLA effects [45]. The tissue dependent differences of action were also evident in mice; t10c12 CLA induced loss of adipose tissue but at the same time decreased fatty acid oxidation and increased fatty acid synthesis in liver [46]. "
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