Yoshimoto K

References (3)

Title : BIMP affects tubulin structure and causes abnormalities in cell division - Murata_2021_Leg.Med.(Tokyo)_53_101929
Author(s) : Murata K , Yoshikawa N , Yoshimoto K , Namera A , Takeshita H , Nagao M
Ref : Leg Med (Tokyo) , 53 :101929 , 2021
Abstract : Although organophosphorus agents are used worldwide as pesticides, there have been many reports of pesticide poisoning. Nerve agents are organophosphorus agents that interfere with neurotransmission and have been used as chemical weapons in wars. These agents mainly irreversibly inhibit the action of acetylcholinesterase, an enzyme that breaks down acetylcholine, a neurotransmitter, and are believed to cause acute symptoms of poisoning. However, in recent years, the presence of subacute, delayed toxicity independent of acetylcholinesterase inhibition has been reported for some organophosphorus agents. We analyzed the subacute and delayed toxicity of bis(isopropylmethyl)phosphonate (BIMP), which has the same phosphonate group as sarin. BIMP rounded out the morphology of the cells and reduced the proportion of cells in the G1 phase of the cell cycle over time. No DNA damage was observed, suggesting that BIMP may affect cell division.
ESTHER : Murata_2021_Leg.Med.(Tokyo)_53_101929
PubMedSearch : Murata_2021_Leg.Med.(Tokyo)_53_101929
PubMedID: 34225093

Title : The sarin-like organophosphorus agent bis(isopropyl methyl)phosphonate induces ER stress in human astrocytoma cells - Arima_2016_J.Toxicol.Sci_41_617
Author(s) : Arima Y , Shiraishi H , Saito A , Yoshimoto K , Namera A , Makita R , Murata K , Imaizumi K , Nagao M
Ref : Journal of Toxicological Sciences , 41 :617 , 2016
Abstract : Organophosphorus (OP) compounds such as sarin are toxic agents that irreversibly inhibit the enzyme acetylcholinesterase. A recent study showed that OP compounds also have multiple toxicity mechanisms, and another suggested that endoplasmic reticulum (ER) dysfunction contributes to OP toxicity. However, the signaling pathway and mechanisms involved are poorly understood. We examined whether the sarin-like OP agent bis(isopropyl methyl)phosphonate (BIMP), which exhibits toxicity similar to that of sarin, induced ER stress in human astrocytoma CCF-STTG1 cells. Our results demonstrate that BIMP exposure reduced cell viability. Moreover, it induced changes in mitochondrial membrane potential and increased cleavage of caspase 3. Treatment with BIMP increased the mRNA levels of the ER stress marker genes binding immunoglobulin protein (BiP) and the transcription factor C/EBP homologous protein (CHOP). Furthermore, BIMP increased the protein expressions and phosphorylation of BiP, CHOP, and protein kinase RNA-like ER kinase and the phosphorylation of eukaryotic translation initiation factor 2. Compared to BIMP treatment alone, pretreatment with the CHOP siRNA, siCHOP, decreased BIMP-dependent CHOP expression and improved CCF-STTG1 cell viability. Our findings suggest that BIMP induced mitochondrial dysfunction and apoptotic cell death event mediated by ER stress in CCF-STTG1 cells and that treatment targeted at managing ER stress has the potential to attenuate the toxicity of OP nerve agents.
ESTHER : Arima_2016_J.Toxicol.Sci_41_617
PubMedSearch : Arima_2016_J.Toxicol.Sci_41_617
PubMedID: 27665771

Title : The Sarin-like Organophosphorus Agent bis (isopropyl methyl)phosphonate Induces Apoptotic Cell Death and COX-2 Expression in SK-N-SH Cells - Arima_2016_Hiroshima.J.Med.Sci_65_1
Author(s) : Arima Y , Yoshimoto K , Namera A , Makita R , Murata K , Nagao M
Ref : Hiroshima J Med Sci , 65 :1 , 2016
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.
ESTHER : Arima_2016_Hiroshima.J.Med.Sci_65_1
PubMedSearch : Arima_2016_Hiroshima.J.Med.Sci_65_1
PubMedID: 27348899