Apoptosis induced by oxidized lipids is associated with up-regulation of p66Shc in intestinal Caco-2 cells: protective effects of phenolic compounds.

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Giovannini C, Scazzocchio B, Matarrese P, Vari R, D'Archivio M, Di Benedetto R, Casciani S, Dessi MR, Straface E, Malorni W, Masella R

Apoptosis induced by oxidized lipids is associated with up-regulation of p66Shc in intestinal Caco-2 cells: protective effects of phenolic compounds.

J Nutr Biochem. 2008 Feb;19(2):118-28. Epub 2007 Jun 27.

PubMed ID

17588737 [ View in PubMed

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Abstract

In this study, we investigated the alterations of the redox balance induced by the lipid fraction of oxLDL in Caco-2 intestinal cells, and the effects of tyrosol and protocatechuic acid, two dietary phenolic compounds. We found that oxidized lipids extracted from oxLDL (LipE) induced oxidative stress by determining, 6 h after treatment, ROS overproduction (about a 100% and a 43% increase of O*2 and H2O2 production, respectively, P<.05: LipE vs. control) and, 12 h after treatment, GSH depletion (about a 26% decrease, P<.05: LipE vs. control), and by impairing the activities of superoxide dismutase, catalase and glutathione peroxidase. In response to the induced oxidative stress, we observed significant overexpression of glutathione peroxidase (6 h after treatment: P<.05), glutathione reductase and gamma-glutamylcysteine synthetase (12 h after treatment: P<.05). Notably, when GSH depletion occurred, p66Shc protein expression increased by about 300% with respect to control (P<.001; LipE vs. control). These effects were fully counteracted by dietary phenolics which inhibited ROS overproduction and GSH consumption, rendered the reactive transcription of glutathione-associated enzymes unnecessary and blocked the intracellular signals leading to the overexpression and rearrangement of p66Shc signalling molecule. Altogether, these results suggest that the impairment of the antioxidant system hijacks intestinal cells towards an apoptotic-prone phenotype via the activation of p66Shc molecule. They also propose a reappraisal of dietary polyphenols as intestinal protecting agents, indicating the antiapoptotic effect as a further mechanism of action of these antioxidant compounds.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Glutathione	Glutathione peroxidase 6	Protein	Humans	Unknown	Cofactor	Details
Glutathione	Glutathione peroxidase 7	Protein	Humans	Unknown	Cofactor	Details