title: The Sarin-like Organophosphorus Agent bis (isopropyl methyl)phosphonate Induces Apoptotic Cell Death and COX-2 Expression in SK-N-SH Cells.
abstract: Organophosphorus compounds, such as sarin, are highly toxic nerve agents that inhibit acetylcholinesterase (AChE), but not cholinesterase, via multiple mechanisms. Recent studies have shown that organophosphorus compounds increase cyclooxygenase-2 (COX-2) expression and induce neurotoxicity. In this study, we examined the toxicity of the sarin-like organophosphorus agent bis(isopropyl methyl)phosphonate (BIMP) and the effects of BIMP on COX-2 expression in SK-N-SH human neuroblastoma cells. Exposure to BIMP changed cell morphology and induced caspase-dependent apoptotic cell death accompanied by cleavage of caspase 3, caspase 9, and poly (ADP-ribose) polymerase (PARP). It also increased COX-2 expression, while pretreatment with a COX inhibitor, ibuprofen, decreased BIMP-dependent cell death and COX-2 expression in SK-N-SH cells. Thus, our findings suggest that BIMP induces apoptotic cell death and upregulates COX-2 expression.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Arima
authors.forename: Kanji
authors.initials: K
authors.lastname: Yoshimoto
authors.forename: Akira
authors.initials: A
authors.lastname: Namera
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Makita
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Murata
authors.forename: Masataka
authors.initials: M
authors.lastname: Nagao
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000032:analysis*; D004164:Diphosphonates / Q000494:pharmacology*; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology; D009447:Neuroblastoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology
chemical_list: D004164:Diphosphonates; C109992:bis(isopropyl methyl)phosphonate; D051546:Cyclooxygenase 2; D007052:Ibuprofen