The Loss of HIF1α Leads to Increased Susceptibility to Cadmium-Chloride-Induced Toxicity in Mouse Embryonic Fibroblasts
Wild-type and HIF1α −/− MEF cells were used to determine the role of HIF1α in cadmium-induced toxicity. Cadmium treatment did not affect HIF1-mediated transcription but led to caspase activation and apoptotic cell death in wild-type and HIF1α −/− cells. Cadmium-induced cell death, however, was signi...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2011-01-01
|
| Series: | Journal of Toxicology |
| Online Access: | http://dx.doi.org/10.1155/2011/391074 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832549867404132352 |
|---|---|
| author | Ajith Vengellur Elizabeth Grier John J. LaPres |
| author_facet | Ajith Vengellur Elizabeth Grier John J. LaPres |
| author_sort | Ajith Vengellur |
| collection | DOAJ |
| description | Wild-type and HIF1α −/− MEF cells were used to determine the role of HIF1α in cadmium-induced toxicity. Cadmium treatment did not affect HIF1-mediated transcription but led to caspase activation and apoptotic cell death in wild-type and HIF1α −/− cells. Cadmium-induced cell death, however, was significantly higher in HIF1α −/− cells as compared to their wild-type counterparts. Increased cell death in the HIF1α −/− cells was correlated with lower metallothionein protein, elevated levels of reactive oxygen species, and decreased superoxide dismutase enzyme activity. The total and oxidized glutathione levels, and, correspondingly, lipid peroxidation levels were elevated in the null cells compared to wild-type cells, indicating increased antioxidant demand and greater oxidative stress. Overall, the results suggest that basal levels of HIF1α play a protective role against cadmium-induced cytotoxicity in mouse embryonic fibroblasts by maintaining metallothionein and antioxidant activity levels. |
| format | Article |
| id | doaj-art-8efd5df039b842baa431d2e6c766250e |
| institution | Kabale University |
| issn | 1687-8191 1687-8205 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Toxicology |
| spelling | doaj-art-8efd5df039b842baa431d2e6c766250e2025-02-03T06:08:23ZengWileyJournal of Toxicology1687-81911687-82052011-01-01201110.1155/2011/391074391074The Loss of HIF1α Leads to Increased Susceptibility to Cadmium-Chloride-Induced Toxicity in Mouse Embryonic FibroblastsAjith Vengellur0Elizabeth Grier1John J. LaPres2Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824-1319, USADepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824-1319, USADepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824-1319, USAWild-type and HIF1α −/− MEF cells were used to determine the role of HIF1α in cadmium-induced toxicity. Cadmium treatment did not affect HIF1-mediated transcription but led to caspase activation and apoptotic cell death in wild-type and HIF1α −/− cells. Cadmium-induced cell death, however, was significantly higher in HIF1α −/− cells as compared to their wild-type counterparts. Increased cell death in the HIF1α −/− cells was correlated with lower metallothionein protein, elevated levels of reactive oxygen species, and decreased superoxide dismutase enzyme activity. The total and oxidized glutathione levels, and, correspondingly, lipid peroxidation levels were elevated in the null cells compared to wild-type cells, indicating increased antioxidant demand and greater oxidative stress. Overall, the results suggest that basal levels of HIF1α play a protective role against cadmium-induced cytotoxicity in mouse embryonic fibroblasts by maintaining metallothionein and antioxidant activity levels.http://dx.doi.org/10.1155/2011/391074 |
| spellingShingle | Ajith Vengellur Elizabeth Grier John J. LaPres The Loss of HIF1α Leads to Increased Susceptibility to Cadmium-Chloride-Induced Toxicity in Mouse Embryonic Fibroblasts Journal of Toxicology |
| title | The Loss of HIF1α Leads to Increased Susceptibility to Cadmium-Chloride-Induced Toxicity in Mouse Embryonic Fibroblasts |
| title_full | The Loss of HIF1α Leads to Increased Susceptibility to Cadmium-Chloride-Induced Toxicity in Mouse Embryonic Fibroblasts |
| title_fullStr | The Loss of HIF1α Leads to Increased Susceptibility to Cadmium-Chloride-Induced Toxicity in Mouse Embryonic Fibroblasts |
| title_full_unstemmed | The Loss of HIF1α Leads to Increased Susceptibility to Cadmium-Chloride-Induced Toxicity in Mouse Embryonic Fibroblasts |
| title_short | The Loss of HIF1α Leads to Increased Susceptibility to Cadmium-Chloride-Induced Toxicity in Mouse Embryonic Fibroblasts |
| title_sort | loss of hif1α leads to increased susceptibility to cadmium chloride induced toxicity in mouse embryonic fibroblasts |
| url | http://dx.doi.org/10.1155/2011/391074 |
| work_keys_str_mv | AT ajithvengellur thelossofhif1aleadstoincreasedsusceptibilitytocadmiumchlorideinducedtoxicityinmouseembryonicfibroblasts AT elizabethgrier thelossofhif1aleadstoincreasedsusceptibilitytocadmiumchlorideinducedtoxicityinmouseembryonicfibroblasts AT johnjlapres thelossofhif1aleadstoincreasedsusceptibilitytocadmiumchlorideinducedtoxicityinmouseembryonicfibroblasts AT ajithvengellur lossofhif1aleadstoincreasedsusceptibilitytocadmiumchlorideinducedtoxicityinmouseembryonicfibroblasts AT elizabethgrier lossofhif1aleadstoincreasedsusceptibilitytocadmiumchlorideinducedtoxicityinmouseembryonicfibroblasts AT johnjlapres lossofhif1aleadstoincreasedsusceptibilitytocadmiumchlorideinducedtoxicityinmouseembryonicfibroblasts |