Cadmium induces apoptotic cell death through p38 MAPK in brain microvessel endothelial cells
| Autor: | Yi-Sook Jung, Soo Hwan Lee, Euy-Myoung Jeong, Seonghyang Sohn, You-Mie Kim, Chang-Hyun Moon, Eun Joo Baik, Eun Kyung Park |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
MAPK/ERK pathway
Programmed cell death Cell Survival Apoptosis Biology p38 Mitogen-Activated Protein Kinases Mice Cadmium Chloride Annexin In Situ Nick-End Labeling Animals Viability assay Annexin A5 Phosphorylation Cells Cultured Pharmacology Dose-Response Relationship Drug Kinase Microcirculation Brain Cell biology Endothelial stem cell Microscopy Electron Blood-Brain Barrier Mitogen-activated protein kinase biology.protein Endothelium Vascular |
| Zdroj: | European Journal of Pharmacology. 578:11-18 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2007.08.049 |
| Popis: | Cadmium (Cd), an ubiquitous heavy metal, is known to be accumulated outside of the blood-brain barrier. In this study, we investigated whether Cd has cytotoxicity in mouse brain microvascular endothelial cells (bEnd.3). Results from the cell viability assay showed that Cd caused a remarkable decrease in cell viability in a dose-dependent manner. The cell death induced by Cd appeared to involve apoptosis, based on our results from annexin V staining, electron microscopy and TUNEL staining. And the cell death induced by Cd was inhibited by caspase inhibitor ZVAD-fmk. To further investigate the mechanism of the Cd-induced cell death, we examined the effects of selective inhibitors for mitogen activated protein kinase (MAPK) pathways on the cell death. The Cd-induced cell death was significantly inhibited by p38 MAPK inhibitor SB202190, but not by either, c-Jun N-terminal kinase (JNK) inhibitor SP600125 or extracellular signal-regulated kinase (ERK) inhibitor U0126. Phosphorylations of p38 MAPK, JNK and ERK were stimulated by treatment with CdCl(2). In summary, our results suggest that Cd can induce apoptotic cell death, at least in part, through the p38 MAPK pathway in brain microvascular endothelial cells. |
| Databáze: | OpenAIRE |
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