title: N-nitrosocarbofuran induces apoptosis in mouse brain microvascular endothelial cells (bEnd.3).
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.
authors.affiliation: Department of Physiology, School of Medicine, Ajou University, Suwon, Korea. yisjung@ajou.ac.kr
authors.forename: Yi-Sook
authors.initials: YS
authors.lastname: Jung
authors.forename: Chan-Sik
authors.initials: CS
authors.lastname: Kim
authors.forename: Hye-Seong
authors.initials: HS
authors.lastname: Park
authors.forename: Seonghyang
authors.initials: S
authors.lastname: Sohn
authors.forename: Byung-Hoon
authors.initials: BH
authors.lastname: Lee
authors.forename: Chang-Kiu
authors.initials: CK
authors.lastname: Moon
authors.forename: Soo Hwan
authors.initials: SH
authors.lastname: Lee
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Baik
authors.forename: Chang-Hyun
authors.initials: CH
authors.lastname: Moon
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000494:pharmacology; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000098:blood supply*; D002235:Carbofuran / Q000031:analogs & derivatives* / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D005419:Flavonoids / Q000494:pharmacology; D005434:Flow Cytometry; D007093:Imidazoles / Q000494:pharmacology; D051379:Mice; D008833:Microcirculation / Q000187:drug effects; D008854:Microscopy, Electron; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D010575:Pesticides / Q000633:toxicity*; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D017304:Annexin A5; D000873:Anthracenes; D005419:Flavonoids; D007093:Imidazoles; C445260:N-nitrosocarbofuran; D010575:Pesticides; D011725:Pyridines; C432165:pyrazolanthrone; D020928:Mitogen-Activated Protein Kinases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D002235:Carbofuran