Expression of macrophage migration inhibitory factor by osteoblastic cells: Protection against cadmium toxicity
| Autor: | Tatiana Scorza, Diane Tshikudi Malu, Jérôme Lizotte, Jaime Sanchez-Dardon, Olha Kevorkova, Jorge Cuevas, Elie Abed, Abhay R. Satoskar, Robert Moreau, Céline Signor, Catherine Jumarie |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Programmed cell death
Biology Toxicology Mice Downregulation and upregulation Nitriles Animals Cytotoxic T cell Sulfones MC3T3 Extracellular Signal-Regulated MAP Kinases Cytotoxicity Macrophage Migration-Inhibitory Factors chemistry.chemical_classification Reactive oxygen species Osteoblasts NF-kappa B 3T3 Cells General Medicine Cell biology Intramolecular Oxidoreductases Gene Expression Regulation chemistry Biochemistry Environmental Pollutants Macrophage migration inhibitory factor Intracellular Cadmium Signal Transduction |
| Zdroj: | Toxicology Letters. 215:167-173 |
| ISSN: | 0378-4274 |
| DOI: | 10.1016/j.toxlet.2012.10.006 |
| Popis: | Exposition to cadmium (Cd) has been linked to bone metabolism alterations and occurrence of osteoporosis. Despite its known renal toxicity which indirectly disrupts bone metabolism through impairment of vitamin D synthesis, increasing evidence argues for the direct action of Cd on bone-forming osteoblasts. Indeed, accumulation of Cd in osteoblasts and metal-induced cell death has been documented but little is known about the intracellular mechanisms of protection against this stress. In this work, we investigated the protection afforded by thiol-containing proteins against Cd cytotoxicity in MC3T3 osteoblastic cells. Viability of MC3T3 cells was reduced by Cd in a concentration-dependent manner with a LC 50 of 7.6 ± 1.1 μM. Depletion of glutathione by l -buthionine sulphoximine (BSO) increased cell sensitivity to Cd cytotoxicity, suggesting the involvement of thiol-containing peptides as a mechanism of protection. Accordingly, Cd was shown to promote progressive depletion of reduced thiol content and to stimulate the production of reactive oxygen species (ROS). Interestingly, low non cytotoxic concentrations of Cd increased the gene expression of macrophage migration inhibitory factor (MIF), also a thiol-containing protein. Inhibition of the transcription factor NFκB prevented Cd-dependent upregulation of MIF expression and consequently, increased Cd cytotoxicity in osteoblasts. Moreover, MIF deficient mouse osteoblasts were more sensitive to Cd cytotoxicity than the corresponding control cells. By gel-filtration chromatography, we demonstrated that MIF acts as a thiol-containing protein and thereby promotes Cd complexation. In accordance with its binding ability, addition of recombinant MIF to the culture medium reduced Cd cytotoxicity. Overall, upregulation of MIF expression by Cd may protect against the cytotoxicity of this metal in the osteoblasts. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect