1. Lipid hydroperoxide‐induced apoptosis in human colonic CaCo‐2 cells is associated with an early loss of cellular redox balance
- Author
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Tak Yee Aw, Yudai Gotoh, Carol A. Rhoads, Tong-Gang Wang, and Merilyn H. Jennings
- Subjects
Poly ADP ribose polymerase ,Cell ,Caspase 3 ,Glutathione ,Biochemistry ,Intestinal epithelium ,Redox ,Cell biology ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,Apoptosis ,Genetics ,medicine ,DNA fragmentation ,Molecular Biology ,Biotechnology - Abstract
Apoptosis plays a critical role in maintaining homeostasis of the intestinal epithelium. Dietary oxidants like peroxidized lipids could perturb cellular redox status and disrupt mucosal turnover. The objective of this study was to delineate the role of lipid hydroperoxide (LOOH) -induced redox shifts in intestinal apoptosis using the human colonic CaCo-2 cell. We found that subtoxic concentrations of LOOH increased CaCo-2 cell apoptosis. This LOOH-induced apoptosis was associated with a significant decrease in the ratio of reduced glutathione-to-oxidized glutathione (GSH/GSSG), which preceded DNA fragmentation by 12 to 14 h, suggesting a temporal relationship between the two events. Oxidation of GSH with the thiol oxidant diamide caused significant decreases in cellular GSH and GSH/GSSG at 15 min that correlated with the activation of caspase 3 (60 min) and cleavage of PARP (120 min), confirming a temporal link between induction of cellular redox imbalance and initiation of apoptotic cell death. These kin... more...
- Published
- 2000
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