An In Vitro Study on Mitochondrial Compensatory Response Induced by Gliadin Peptides in Caco-2 Cells
Dietary gliadin may show a broad spectrum of toxicity. The interplay between mitochondria and gliadin-induced oxidative stress has not been thoroughly examined in the intestinal epithelium. In this kinetic study, Caco-2 cells were exposed for 24 h to pepsin-trypsin-digested gliadin, alone or in comb...
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2019-04-01
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author | Antonella Orlando Guglielmina Chimienti Vito Pesce Flavio Fracasso Angela Maria Serena Lezza Francesco Russo |
author_facet | Antonella Orlando Guglielmina Chimienti Vito Pesce Flavio Fracasso Angela Maria Serena Lezza Francesco Russo |
author_sort | Antonella Orlando |
collection | DOAJ |
description | Dietary gliadin may show a broad spectrum of toxicity. The interplay between mitochondria and gliadin-induced oxidative stress has not been thoroughly examined in the intestinal epithelium. In this kinetic study, Caco-2 cells were exposed for 24 h to pepsin-trypsin-digested gliadin, alone or in combination with the antioxidant 2,6-di-tbutyl-p-cresol (BHT), and the effects on mitochondrial biogenesis and mtDNA were studied. Cells ability to recover from stress was determined after 24 h and 48 h of incubation in the culture medium. Gliadin-induced oxidative stress evoked a compensatory response. The stressor triggered a rapid and significant increase of Peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α) and Peroxiredoxin III (PrxIII) proteins, and mtDNA amount. As for the effects of gliadin on mtDNA integrity, strand breaks, abasic sites, and modified bases were analyzed in three mtDNA regions. D-loop appeared a more fragile target than Ori-L and ND1/ND2. The temporal trend of the damage at D-loop paralleled that of the amount of mtDNA. Overall, a trend toward control values was shown 48 h after gliadin exposure. Finally, BHT was able to counteract the effects of gliadin. Results from this study highlighted the effects of gliadin-induced oxidative stress on mitochondria, providing valuable evidence that might improve the knowledge of the pathophysiology of gluten-related disorders. |
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issn | 1422-0067 |
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spelling | doaj.art-6e5c78b553b84414a0f48fe89b6540622022-12-22T02:41:50ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-04-01208186210.3390/ijms20081862ijms20081862An In Vitro Study on Mitochondrial Compensatory Response Induced by Gliadin Peptides in Caco-2 CellsAntonella Orlando0Guglielmina Chimienti1Vito Pesce2Flavio Fracasso3Angela Maria Serena Lezza4Francesco Russo5Laboratory of Nutritional Pathophysiology, National Institute of Gastroenterology “S. de Bellis”, Research Hospital, 70013 Castellana Grotte (Bari), ItalyDepartment of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo Moro, Via Orabona 4, 70100 Bari, ItalyDepartment of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo Moro, Via Orabona 4, 70100 Bari, ItalyDepartment of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo Moro, Via Orabona 4, 70100 Bari, ItalyDepartment of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo Moro, Via Orabona 4, 70100 Bari, ItalyLaboratory of Nutritional Pathophysiology, National Institute of Gastroenterology “S. de Bellis”, Research Hospital, 70013 Castellana Grotte (Bari), ItalyDietary gliadin may show a broad spectrum of toxicity. The interplay between mitochondria and gliadin-induced oxidative stress has not been thoroughly examined in the intestinal epithelium. In this kinetic study, Caco-2 cells were exposed for 24 h to pepsin-trypsin-digested gliadin, alone or in combination with the antioxidant 2,6-di-tbutyl-p-cresol (BHT), and the effects on mitochondrial biogenesis and mtDNA were studied. Cells ability to recover from stress was determined after 24 h and 48 h of incubation in the culture medium. Gliadin-induced oxidative stress evoked a compensatory response. The stressor triggered a rapid and significant increase of Peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α) and Peroxiredoxin III (PrxIII) proteins, and mtDNA amount. As for the effects of gliadin on mtDNA integrity, strand breaks, abasic sites, and modified bases were analyzed in three mtDNA regions. D-loop appeared a more fragile target than Ori-L and ND1/ND2. The temporal trend of the damage at D-loop paralleled that of the amount of mtDNA. Overall, a trend toward control values was shown 48 h after gliadin exposure. Finally, BHT was able to counteract the effects of gliadin. Results from this study highlighted the effects of gliadin-induced oxidative stress on mitochondria, providing valuable evidence that might improve the knowledge of the pathophysiology of gluten-related disorders.https://www.mdpi.com/1422-0067/20/8/1862Caco-2 cellsgliadingluten-related disordersmitochondrial biogenesismtDNAmtDNA damageoxidative stressPGC-1αPrxIII |
spellingShingle | Antonella Orlando Guglielmina Chimienti Vito Pesce Flavio Fracasso Angela Maria Serena Lezza Francesco Russo An In Vitro Study on Mitochondrial Compensatory Response Induced by Gliadin Peptides in Caco-2 Cells International Journal of Molecular Sciences Caco-2 cells gliadin gluten-related disorders mitochondrial biogenesis mtDNA mtDNA damage oxidative stress PGC-1α PrxIII |
title | An In Vitro Study on Mitochondrial Compensatory Response Induced by Gliadin Peptides in Caco-2 Cells |
title_full | An In Vitro Study on Mitochondrial Compensatory Response Induced by Gliadin Peptides in Caco-2 Cells |
title_fullStr | An In Vitro Study on Mitochondrial Compensatory Response Induced by Gliadin Peptides in Caco-2 Cells |
title_full_unstemmed | An In Vitro Study on Mitochondrial Compensatory Response Induced by Gliadin Peptides in Caco-2 Cells |
title_short | An In Vitro Study on Mitochondrial Compensatory Response Induced by Gliadin Peptides in Caco-2 Cells |
title_sort | in vitro study on mitochondrial compensatory response induced by gliadin peptides in caco 2 cells |
topic | Caco-2 cells gliadin gluten-related disorders mitochondrial biogenesis mtDNA mtDNA damage oxidative stress PGC-1α PrxIII |
url | https://www.mdpi.com/1422-0067/20/8/1862 |
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