Conjugated linoleic acid isomers' roles in the regulation of PPAR-gamma and NF-kappa B 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: 3.05). 04/2009; 25(7-8):800-11. DOI: 10.1016/j.nut.2009.01.003
Source: PubMed

ABSTRACT 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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In addition to exhibiting antioxidant properties, conjugated linoleic acid (CLA) and vitamin E may modulate gene expression of endogenous antioxidant enzymes. Depending on cellular microenvironments, such modulation reflects either antioxidant or prooxidant outcomes. Although epidemiological/experimental studies have indicated that CLA and vitamin E have health promoting properties, recent findings from clinical trials have been inconclusive. Discrepancies between the results found from prospective studies and recent clinical trials might be attributed to concentration-dependent cellular microenvironment alterations. We give a perspective of possible molecular mechanisms of actions of these lipophilic compounds and their implications for interventions of reactive oxygen species (ROS)-related diseases.
    Nutrients 07/2010; 2(7):725-36. DOI:10.3390/nu2070725 · 3.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The bone undergoes continuous remodeling of osteoblastic bone formation and osteoclastic bone resorption to maintain proper bone mass. It is also reported that bone marrow adiposity has a reciprocal role in osteoblasts due to their same origin from mesenchymal stem cells. In addition, one of the key mediators of adipogenesis, peroxisome-proliferator activated receptor-γ (PPARγ), plays a significant role in osteoblastogenesis in bone marrow mesenchymal stem cells. One dietary component that is known to have significant impact on adiposity and bone mass is conjugated linoleic acid (CLA). However, the link between controlling adiposity to improving bone mass by CLA has not been studied intensively. Thus, the purpose of this study is to determine the role of CLA on bone marrow adiposity and bone formation using murine mesenchymal stem cells. The results confirmed that the trans-10,cis-12 CLA, but not the cis-9,trans-11 CLA isomer, significantly inhibited adipogenesis and promoted osteoblastogenesis from mesenchymal stem cells. The inhibition of adipogenesis by the trans-10,cis-12 CLA was mediated by PPARγ; however, the trans-10,cis-12 CLA had a direct effect on osteoblastogenesis which was independent to PPARγ in this model. The trans-10,cis-12 CLA also had significant effects on osteoclastogenesis inhibitory factor, which suggests potential influence of CLA on osteoclastogenesis. Overall, the results suggest that the trans-10,cis-12, but not the cis-9,trans-11 CLA isomer, has a positive impact on bone health by both PPARγ mediated and independent mechanisms in mesenchymal stem cells.
    The Journal of nutritional biochemistry 07/2012; DOI:10.1016/j.jnutbio.2012.03.017 · 4.29 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to determine the effects of trans-10, cis-12 conjugated linoleic acid (t10c12 CLA) supplementation on oocyte maturation and embryo development in pigs. Compared with the control, supplementation of 50 µM t10c12 CLA to in vitro maturation (IVM) medium significantly increased the proportion of oocytes at the metaphase II (MII) stage and subsequent parthenogenetic embryo development in terms of cleavage rate, blastocyst formation rate, and cell numbers in blastocysts. The t10c12 CLA-treated oocytes resumed meiotic maturation and progressed to the MII stage significantly faster than those of control. The expression of phosphorylated mitogen-activated protein kinase 3/1 (p-MAPK3/1) and cyclooxygenase-2 (COX2) in cumulus oocyte complexes (COCs) at 5, 10, and 22 h of IVM were significantly increased in the t10c12 CLA-treatment group. The level of p-MAPK3/1 in t10c12 CLA-treated MII oocytes was also higher (P <0.05) than that of control. Moreover, t10c12 CLA supplementation partially overcame the negative effects of U0126 on cumulus expansion and nuclear maturation, and completely recovered COX2 protein levels in the presence of U0126. Treatment of COCs with NS398 also significantly suppressed cumulus expansion and nuclear maturation, which was overcome by t10c12 CLA. Yet, this simulatory effect of t10c12 CLA was blocked in the presence of both U0126 and NS398. The t10c12 CLA treatment significantly reduced reactive oxygen species level and increased glutathione concentrations in MII oocyte. In conclusion, supplementation of t10c12 CLA during porcine oocyte maturation exerts its beneficial effects on nuclear and cytoplasmic maturation, which contributes to enhancing subsequent embryo development. Mol. Reprod. Dev. © 2013 Wiley Periodicals, Inc.
    Molecular Reproduction and Development 01/2014; 81(1). DOI:10.1002/mrd.22273 · 2.68 Impact Factor