Cadmium induces apoptotic cell death through p38 MAPK in brain microvessel endothelial cells.
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.
Jung
Yi-Sook
YS
Department of Physiology, School of Medicine, Ajou University, Suwon 443-749, Republic of Korea.
Jeong
Euy-Myoung
EM
Park
Eun Kyung
EK
Kim
You-Mie
YM
Sohn
Seonghyang
S
Lee
Soo Hwan
SH
Baik
Eun Joo
EJ
Moon
Chang-Hyun
CH
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000098:blood supply; D019256:Cadmium Chloride / Q000008:administration & dosage / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D051379:Mice; D008833:Microcirculation / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008854:Microscopy, Electron; D010766:Phosphorylation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism
D017304:Annexin A5; D048051:p38 Mitogen-Activated Protein Kinases; D019256:Cadmium Chloride