The Sarin-like Organophosphorus Agent bis(isopropyl methyl)phosphonate Induces Apoptotic Cell Death and COX-2 Expression in SK-N-SH Cells

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Title ( eng )
The Sarin-like Organophosphorus Agent bis(isopropyl methyl)phosphonate Induces Apoptotic Cell Death and COX-2 Expression in SK-N-SH Cells
Creator
Arima Yosuke
Yoshimoto Kanji
Makita Ryosuke
Source Title
Hiroshima Journal of Medical Sciences
Volume 65
Issue 1
Start Page 1
End Page 8
Journal Identifire
[PISSN] 0018-2052
[EISSN] 2433-7668
[NCID] AA00664312
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.
Keywords
Sarin
Organophosphates
Apoptosis
COX-2
NDC
Medical sciences [ 490 ]
Language
eng
Resource Type departmental bulletin paper
Publisher
Hiroshima University Medical Press
Date of Issued 2016-03
Rights
Copyright (c) 2016 Hiroshima University Medical Press
Publish Type Version of Record
Access Rights open access
Source Identifier
[ISSN] 0018-2052
[NCID] AA00664312