Iron-Ascorbate-Mediated Lipid Peroxidation

[ironjustice]

Iron-Ascorbate-Mediated Lipid Peroxidation Causes Epigenetic Changes
in the Antioxidant Defense in Intestinal Epithelial Cells: Impact on
Inflammation
Sabrina Yara, Affiliation: Department of Nutrition, Research Centre,
CHU-Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada
X Jean-Claude Lavoie, Affiliation: Department of Pediatrics, Research
Centre, CHU-Sainte-Justine, Université de Montréal, Montreal, Quebec,
Canada
X Jean-François Beaulieu, Affiliation: Canadian Institutes for Health
Research Team on the Digestive Epithelium, Department of Anatomy and
Cellular Biology, Faculty of Medicine and Health Sciences, Université
de Sherbrooke, Sherbrooke, Quebec, Canada
X Edgard Delvin, Affiliation: Department of Biochemistry, Research
Centre, CHU-Sainte-Justine, Université de Montréal, Montreal, Quebec,
Canada
X Devendra Amre, Affiliation: Department of Pediatrics, Research
Centre, CHU-Sainte-Justine, Université de Montréal, Montreal, Quebec,
Canada
X Valerie Marcil, Affiliation: Research Institute, McGill University,
Campus MGH, C10.148.6, Montreal, Quebec, Canada
X Ernest Seidman, Affiliations: Research Institute, McGill University,
Campus MGH, C10.148.6, Montreal, Quebec, Canada, Canadian Institutes
for Health Research Team on the Digestive Epithelium, Department of
Anatomy and Cellular Biology, Faculty of Medicine and Health Sciences,
Université de Sherbrooke, Sherbrooke, Quebec, Canada
X Emile Levy

Abstract
Introduction
The gastrointestinal tract is frequently exposed to noxious stimuli
that may cause oxidative stress, inflammation and injury. Intraluminal
pro-oxidants from ingested nutrients especially iron salts and
ascorbic acid frequently consumed together, can lead to catalytic
formation of oxygen-derived free radicals that ultimately overwhelm
the cellular antioxidant defense and lead to cell damage.

Hypothesis
Since the mechanisms remain sketchy, efforts have been exerted to
evaluate the role of epigenetics in modulating components of
endogenous enzymatic antioxidants in the intestine. To this end,
Caco-2/15 cells were exposed to the iron-ascorbate oxygen radical-
generating system.

Results
Fe/Asc induced a significant increase in lipid peroxidation as
reflected by the elevated formation of malondialdehyde along with the
alteration of antioxidant defense as evidenced by raised superoxide
dismutase 2 (SOD2) and diminished glutathione peroxidase (GPx)
activities and genes. Consequently, there was an up-regulation of
inflammatory processes illustrated by the activation of NF-κB
transcription factor, the higher production of interleukin-6 and
cycloxygenase-2 as well as the decrease of IκB. Assessment of
promoter’s methylation revealed decreased levels for SOD2 and
increased degree for GPx2. On the other hand, pre-incubation of
Caco-2/15 cells with 5-Aza-2′-deoxycytidine, a demethylating agent, or
Trolox antioxidant normalized the activities of SOD2 and GPx, reduced
lipid peroxidation and prevented inflammation.

Conclusion
Redox and inflammatory modifications in response to Fe/Asc -mediated
lipid peroxidation may implicate epigenetic methylation.

Citation: Yara S, Lavoie J-C, Beaulieu J-F, Delvin E, Amre D, et al.
(2013) Iron-Ascorbate-Mediated Lipid Peroxidation Causes Epigenetic
Changes in the Antioxidant Defense in Intestinal Epithelial Cells:
Impact on Inflammation. PLoS ONE 8(5): e63456. doi:10.1371/
journal.pone.0063456

Editor: Yoshiaki Tsuji, North Carolina State University, United States
of America


Received: January 1, 2013; Accepted: April 3, 2013; Published: May 22,
2013

Copyright: © 2013 Yara et al. This is an open-access article
distributed under the terms of the Creative Commons Attribution
License, which permits unrestricted use, distribution, and
reproduction in any medium, provided the original author and source
are credited.

Funding: This study was supported by the J. A. DeSève Research Chair
in Nutrition. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0063456

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[John H. Gohde]

To Quote Ken ...

Only a Mentally Unbalanced Obsessive Compulsive Quack like Chung da
Chink would
spend several hours EVERY DAY endlessly repeating his same worthless,
mindless,
pointless, useless BULLSHIT that everyone ignores.

Moi say what is bad for that nut-job, applies equally to ironjustice.