Gastrointestinal glutathione peroxidase prevents transport of lipid hydroperoxides in CaCo-2 cells

Wingler, Kirstin; Müller, Cordula; Schmehl, K.; Florian, Simone; Brigelius‐Flohé, Regina

doi:10.1053/gast.2000.9521

Cited by 85 publications

(51 citation statements)

References 49 publications

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“…(i) GI-GPx mRNA is extremely stable in selenium deficiency, which ranks GI-GPx high in the hierarchy of selenoproteins and, thus, points to more vital functions than those the low-ranking selenoproteins such as cGPx may have (45,65). (ii) In accordance with the high mRNA stability, GI-GPx protein is synthesized first upon selenium resupplementation, while cGPx follows with a delay of at least 24 h, as has been demonstrated in vitro and in vivo (10,66). (iii) Unlike cGPx, GI-GPx is not uniformly expressed along the crypt-tovillus axis but is preferentially located in the crypts (22).…”

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confidence: 76%

“…In a CaCo-2 cell model, selenium deficiency and the resulting decrease in glutathione peroxidase activity indeed led to a higher release of hydroperoxides to the basolateral side. This was paralleled by damage to the cell membrane and could be prevented by selenium concentrations sufficient to restore GI-GPx expression but not the classical GPx (cGPx, GPx1) (66).…”

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confidence: 99%

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The GI-GPx Gene Is a Target for Nrf2

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Deubel

Kluth

et al. 2005

Molecular and Cellular Biology

299

115

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The gastrointestinal glutathione peroxidase (GI-GPx, GPx2) is a selenoprotein that was suggested to act as barrier against hydroperoxide absorption but has also been implicated in the control of inflammation and malignant growth. In CaCo-2 cells, GI-GPx was induced by t-butyl hydroquinone (tBHQ) and sulforaphane (SFN), i.e., "antioxidants" known to activate the "antioxidant response element" (ARE) via electrophilic thiol modification of Keap1 in the Nrf2/Keap1 system. The functional significance of a putative ARE in the GI-GPx promoter was validated by transcriptional activation of reporter gene constructs upon exposure to electrophiles (tBHQ, SFN, and curcumin) or overexpression of Nrf2 and by reversal of these effects by mutation of the ARE in the promoter and by overexpressed Keap1. Binding of Nrf2 to the ARE sequence in authentic gpx2 was corroborated by chromatin immunoprecipitation. Thus, the presumed natural antioxidants sulforaphane and curcumin may exert their anti-inflammatory and anticarcinogenic effects not only by induction of phase 2 enzymes but also by the up-regulation of the selenoprotein GI-GPx.

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mentioning

confidence: 76%

mentioning

confidence: 99%

The GI-GPx Gene Is a Target for Nrf2

Banning

Deubel

Kluth

et al. 2005

Molecular and Cellular Biology

299

115

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“…In the gastrointestinal tract, a defense system including gastrointestinal glutathione peroxidase is known to detoxify and degrade lipid peroxidation products ( 34 ), and protect against infl ammation ( 35 ). Feeding animals with highly oxidized n -6 fat was reported to increase the expression of markers of intestine antioxidant defense ( 36,37 ).…”

Section: Discussionmentioning

confidence: 99%

Dietary oxidized n-3 PUFA induce oxidative stress and inflammation: role of intestinal absorption of 4-HHE and reactivity in intestinal cells

Awada

Soulage

Meynier

et al. 2012

Journal of Lipid Research

174

154

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“…Effects of H 2 O 2 and Diamide on CaCo2 Cells-To confirm and generalize the results obtained in AGS cells, we selected another adenocarcinoma cell line, CaCo2, which has been reported to express GI-glutathione peroxidase (27,28). However, in contrast to AGS, these cells express a truncated/null form of p53 (29).…”

Section: Nrf2-and P53-mediated Response To Oxidative Stressmentioning

confidence: 94%

Redox Mechanisms Involved in the Selective Activation of Nrf2-mediated Resistance Versus p53-dependent Apoptosis in Adenocarcinoma Cells

Piccirillo

Filomeni

Brüne

et al. 2009

Journal of Biological Chemistry

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We have investigated the role of reactive oxygen species and thiol-oxidizing agents in the induction of cell death and have shown that adenocarcinoma gastric (AGS) cells respond differently to the oxidative challenge according to the signaling pathways activated. In particular, apoptosis in AGS cells is induced via the mitochondrial pathway upon treatment with thiol-oxidizing agents, such as diamide. Apoptosis is associated with persistent oxidative damage, as evidenced by the increase in carbonylated proteins and the expression/activation of DNA damage-sensitive proteins histone H2A.X and DNA-dependent protein kinase. Resistance to hydrogen peroxide is instead associated with Keap1 oxidation and rapid translocation of Nrf2 into the nucleus. Sensitivity to diamide and resistance to hydrogen peroxide are correlated with GSH redox changes, with diamide severely increasing GSSG, and hydrogen peroxide transiently inducing protein-GSH mixed disulfides. We show that p53 is activated in response to diamide treatment by the oxidative induction of the Trx1/p38 MAPK signaling pathway. Similar results were obtained with another carcinoma cell line, CaCo2, indicating that these findings are not limited to AGS cells. Our data suggest that thiol-oxidizing agents could be exploited as inducers of apoptosis in tumor histotypes resistant to ROS-producing chemotherapeutics.

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Gastrointestinal glutathione peroxidase prevents transport of lipid hydroperoxides in CaCo-2 cells

Cited by 85 publications

References 49 publications

The GI-GPx Gene Is a Target for Nrf2

The GI-GPx Gene Is a Target for Nrf2

Dietary oxidized n-3 PUFA induce oxidative stress and inflammation: role of intestinal absorption of 4-HHE and reactivity in intestinal cells

Redox Mechanisms Involved in the Selective Activation of Nrf2-mediated Resistance Versus p53-dependent Apoptosis in Adenocarcinoma Cells

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