Zinc interference with Cd-induced hormetic effect in differentiated Caco-2 cells: Evidence for inhibition downstream ERK activation
| Autor: | Myriam Mireault, Catherine Jumarie, Joannie Lemaire |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway MAP Kinase Signaling System Health Toxicology and Mutagenesis Cell Stimulation Toxicology Biochemistry 03 medical and health sciences 0302 clinical medicine Hormesis medicine Humans Molecular Biology chemistry.chemical_classification Mitogen-Activated Protein Kinase 1 Reactive oxygen species Mitogen-Activated Protein Kinase 3 030102 biochemistry & molecular biology Chemistry EIF4E Cell Differentiation General Medicine Intestinal epithelium Cell biology Enzyme Activation Zinc medicine.anatomical_structure Caco-2 030220 oncology & carcinogenesis Molecular Medicine Caco-2 Cells Cadmium |
| Zdroj: | Journal of biochemical and molecular toxicologyREFERENCES. 34(3) |
| ISSN: | 1099-0461 |
| Popis: | Cadmium (Cd) is a toxic metal that enters the food chain. Following oral ingestion, the intestinal epithelium represents an effective protective barrier against Cd toxicity, but it is also a target tissue that may accumulate and trap high levels of the ingested metal. Using human enterocytic-like Caco-2 cells, we have previously shown that Cd may induce a concentration and time-dependent increase in 3-(4,5-dimethyl-2-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT)-reducing activity in differentiated cultures with correlation to ERK1/2 activation. The present study shows that (a) Zn prevents the Cd-induced hormesis effect on MTT reduction in a concentration-dependent manner, without inhibiting Cd-induced ERK1/2 activation; (b) Zn also induces similar hormetic stimulation of MTT-reducing activity but without ERK1/2 activation. The effect of both metals was sensitive to inhibitors of translation during protein synthesis. There is evidence for the involvement of reactive oxygen species (ROS) in Cd-induced ERK1/2 activation. In contrast, the Zn effect on the MTT-reducing activity would not be triggered by ROS but it would be sensitive to the redox state of the cell. Steps downstream ERK1/2 activation by Cd does not involve eIF4E which is rather downregulated by Cd. In conclusion, Cd and Zn both can modify translation processes during protein synthesis via different signaling cascades with crosstalk, and cross-inhibition may occur. This phenomenon is observed over a small range of metal concentrations and is characterized by a hormesis-like response. Considering that the hormetic effect on dehydrogenase activity could reflect an adaptive response to the metals whether cross-inhibition is beneficial is an open question. |
| Databáze: | OpenAIRE |
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