2005 Fiscal Year Final Research Report Summary
Investigation of mechanism of non-cholinergic toxicity at acute sarine poisoning
| Project/Area Number |
15591920
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Emergency medicine
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| Research Institution | Nagoya City University |
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Principal Investigator |
NAGAO Masataka Nagoya City University, Graduate School of Medical Sciences, Professor, 大学院・医学研究科, 教授 (80227991)
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| Co-Investigator(Kenkyū-buntansha) |
MAENO Yoshitaka Nagoya City University, Graduate School of Medical Sciences, Associate Professor, 大学院・医学研究科, 助教授 (00145749)
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| Project Period (FY) |
2003 – 2005
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| Keywords | sarine / soman / astrocyte / MAP kinase |
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| Research Abstract |
There are various toxic chemicals that cause cell death. However. in certain cases deleterious agents elicit various cellular responses prior to cell death. To determine the cellular mechanisms by which such cellular responses arc induced is important, but sufficient attention has not been paid to this issue to date. In this study, we showed the characteristic effects of an organophosphorus (OP) agent, bis (pinacolyl methyl) phosphonate (BPMP), which we synthesized for the study of OP nerve agents, on cultured rat astrocytes. Morphologically, BPMP induced cytoplasmic vacuolation and stellation in the rat astrocytes. Cytoplasmic vacuolation is a cell pathological change observed, for example, in vacuolar degeneration, and stellation has been reported in astrocytic reactions against various stimuli. By pretreatment with cycloheximide, a protein synthesis inhibitor, stellation was inhibited, although vacuolation was not. Cell staining with a mitochondrion-selective dye indicated that the vacuolation probably occurs in the mitochondria that are swollen and vacuolatred in the center. Interestingly. the extracellular signal-regulated kinase (ERK) cascade inhibitor inhibited vacuolation and, to some extent, stellation. These results suggest that the ERK signaling cascade is important for the induction of mitochondrial vacuolation. We expect that a detailed study of these astrocytic reactions will provide us new perspectives regarding the variation and pathological significance of cell morphological changes, such as vacuolar degeneration, and also the mechanisms underlying various neurological disorders.
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