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N-nitrosocarbofuran induces apoptosis in mouse brain microvascular endothelial cells (bEnd.3).

Authors
Jung, YS; Kim, CS; Park, HS; Sohn, S; Lee, BH; Moon, CK; Lee, SH; Baik, EJ; Moon, CH
Citation
Journal of pharmacological sciences, 93(4):489-495, 2003
Journal Title
Journal of pharmacological sciences
ISSN
1347-86131347-8648
Abstract
In this study, we investigated whether carbofuran, a commonly used carbamate pesticide, and N-nitrosocarbofuran (NOCF), the N-nitroso metabolite of carbofuran, have cytotoxicity in mouse brain microvascular endothelial cells (bEnd.3). Results from the MTT assay in bEnd.3 cells showed that NOCF but not carbofuran caused a remarkable decrease in cell viability. The cell death induced by NOCF appeared to involve apoptosis, based on our results from annexin V staining and electron microscopy. To investigate the mechanism of the NOCF-induced cell death, we examined the effects of selective inhibitors for MAP kinase pathways, PD98059 (for MEK/ERK), SB202190 (for p38 MAP kinase), and SP600125 (for JNK), on the NOCF-induced cell death. The NOCF-induced cell death was significantly reduced by PD98059, but not by SB202190 or SP600125. NOCF increased ERK phosphorylation as early as 15 min after the treatment and this increase was maintained for 2 h. In summary, our results suggest that NOCF can induce apoptotic cell death, at least in part, through the ERK pathway in brain microvascular endothelial cells.
MeSH terms
AnimalsAnnexin A5/pharmacologyAnthracenes/pharmacologyApoptosis/drug effects*Brain/blood supply*Carbofuran/analogs & derivatives*Carbofuran/toxicity*Cell Survival/drug effectsCells, CulturedEndothelium, Vascular/cytologyEndothelium, Vascular/drug effects*Endothelium, Vascular/enzymologyFlavonoids/pharmacologyFlow CytometryImidazoles/pharmacologyMiceMicrocirculation/drug effectsMicroscopy, ElectronMitogen-Activated Protein Kinases/antagonists & inhibitorsMitogen-Activated Protein Kinases/physiologyPesticides/toxicity*Pyridines/pharmacologySignal TransductionTime Factors
PMID
14737022
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, 이숙손, 성향이, 수환백, 은주문, 창현
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