Investigation of mechanism of non-cholinergic toxicity at acute sarine poisoning

有多种有毒化学物质会导致细胞死亡。然而.在某些情况下，有害物质在细胞死亡之前引发各种细胞反应。确定诱导这种细胞反应的细胞机制是重要的，但迄今为止尚未对该问题给予足够的关注。在这项研究中，我们表现出的特征影响的有机磷（OP）剂，双（甲基）膦酸频哪醇酯（BPMP），我们合成的OP神经毒剂的研究，对培养的大鼠星形胶质细胞。形态学上，BPMP诱导大鼠星形胶质细胞胞浆空泡化和集群。细胞质空泡化是一种观察到的细胞病理学变化，例如，在空泡变性中观察到，并且在星形胶质细胞对各种刺激的反应中已经报道了星座。蛋白质合成抑制剂放线菌酮预处理，抑制星座，但空泡化没有。细胞染色表明，空泡化可能发生在线粒体肿胀和空泡化的中心。很有趣。细胞外信号调节激酶（ERK）级联抑制剂抑制空泡化，并在一定程度上抑制星座形成。这些结果表明，ERK信号级联是重要的诱导线粒体空泡化。我们期望，这些星形胶质细胞反应的详细研究将为我们提供新的观点的变化和病理意义的细胞形态学变化，如空泡变性，也是各种神经系统疾病的机制。

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.