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Cadmium induces apoptotic cell death through p38 MAPK in brain microvessel endothelial cells.

Jung, YS; Jeong, EM; Park, EK; Kim, YM; Sohn, S; Lee, SH; Baik, EJ; Moon, CH
European journal of pharmacology, 578(1):11-18, 2008
Journal Title
European journal of pharmacology
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.
MeSH terms
AnimalsAnnexin A5/metabolismApoptosis/drug effects*Blood-Brain Barrier/metabolismBrain/blood supplyCadmium Chloride/administration & dosageCadmium Chloride/toxicity*Cell Survival/drug effectsCells, CulturedDose-Response Relationship, DrugEndothelium, Vascular/cytologyEndothelium, Vascular/drug effects*Endothelium, Vascular/metabolismIn Situ Nick-End LabelingMiceMicrocirculation/cytologyMicrocirculation/drug effectsMicrocirculation/metabolismMicroscopy, ElectronPhosphorylation/drug effectsp38 Mitogen-Activated Protein Kinases/drug effects*p38 Mitogen-Activated Protein Kinases/metabolism
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
AJOU Authors
정, 이숙김, 유미손, 성향이, 수환백, 은주문, 창현
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