Cadmium-induced decrease in RUNX2 mRNA expression and recovery by the antioxidant N-acetylcysteine (NAC) in the human osteoblast-like cell line, Saos-2
| Autor: | Spenser S. Smith, Kate S. Arbon, Sara J. Heggland, Jackeline Rodriguez Reyes, Wendy A. Harvey, Lindsey M. Hunt |
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| Rok vydání: | 2009 |
| Předmět: |
inorganic chemicals
medicine.medical_specialty Cell Survival Gene Expression Apoptosis Core Binding Factor Alpha 1 Subunit Biology Cadmium chloride Toxicology medicine.disease_cause Article Acetylcysteine Lipid peroxidation chemistry.chemical_compound Cadmium Chloride Cell Line Tumor Internal medicine medicine Humans RNA Messenger chemistry.chemical_classification Osteosarcoma Reactive oxygen species Osteoblasts Dose-Response Relationship Drug Osteoblast Free Radical Scavengers General Medicine Glutathione Oxidative Stress Endocrinology medicine.anatomical_structure chemistry Biochemistry Environmental Pollutants Lipid Peroxidation Reactive Oxygen Species Drug Antagonism Oxidative stress medicine.drug |
| Zdroj: | Toxicology in Vitro. 23:60-66 |
| ISSN: | 0887-2333 |
| DOI: | 10.1016/j.tiv.2008.10.011 |
| Popis: | Exposure to cadmium poses a threat to human health, including increased susceptibility to developing the bone disease osteoporosis. Despite its recognized importance as an environmental toxin, little is known about how cadmium directly impacts bone-forming osteoblasts. We previously reported that cadmium induces apoptosis in human osteoblast-like Saos-2 cells. In this work, we hypothesize that cadmium exposure induces oxidative stress which leads to decreased RUNX2 mRNA expression and increased apoptotic death, and predict that the antioxidant NAC mitigates the damaging effects of cadmium. Oxidative stress is implicated in osteoporosis; furthermore the osteoblast transcriptional factor RUNX2 is reported to play a protective role against osteoporosis in postmenopausal women. Cells treated with 10 microM CdCl2 exhibited signs of oxidative damage including depletion in glutathione, increased reactive oxygen species formation, and enhanced lipid peroxidation. RUNX2 mRNA expression, by RT-PCR, was significantly reduced after exposure to 10 microM CdCl2. Pretreatment with the antioxidant NAC (1mM) prevented cadmium-induced decrease in RUNX2 mRNA and protected cells from apoptotic death. This study provides insight into the mechanisms underlying cadmium-induced osteotoxicity. In addition, this study distinguishes itself by identifying RUNX2 as a target for heavy metal-induced osteotoxicity. |
| Databáze: | OpenAIRE |
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