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Activation of mitochondria-mediated apoptotic pathway in tri-ortho-cresyl phosphate-induced delayed neuropathy

机译:线粒体介导的凋亡通路在三邻甲苯基磷酸酯诱导的迟发性神经病中的激活

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Previous studies suggest that abnormal neurons death has been implicated in organophosphate-induced delayed neuropathy (OPIDN). However, the precise mechanism of neuronal death in OPIDN remains largely unknown. In this study, adult hens were treated with a dosage of 750 mg/kg tri-ortho-cresyl phosphate (TOCP) by gavage, and then sacrificed on the time-points of 1, 5, 10, and 21 days after dosing TOCP, respectively. The apoptotic change of spinal cord neurons induced by TOCP was examined, and the role of mitochondria-mediated apoptosis of neurons during OPIDN was investigated. TUNEL assays showed that apoptotic neurons in hen spinal cords began to appear on day 5 following TOCP exposure. Immunohistochemistry and western blot analysis revealed a translocation of cytochrome C from mitochondria to cytoplasm after dosing TOCP. Moreover, the level of Bcl-2, Bcl-xl, Pro-caspase3 and Pro-caspase9 in hen spinal cord was significantly decreased, whereas that of Bax and cleaved-PARP was significantly elevated. Taken together, these findings indicate that the administration of TOCP can induce neuron apoptosis in hen spinal cords, which might be mediated by the activation of mitochondrial apoptotic pathway.
机译:先前的研究表明,异常的神经元死亡与有机磷酸酯诱导的迟发性神经病(OPIDN)有关。然而,OPIDN中神经元死亡的确切机制仍然未知。在这项研究中,成年雌鸡通过管饲法以750 mg / kg磷酸三原甲酚酯(TOCP)进行处理,然后在给药TOCP后的1、5、10和21天的时间点处死,分别。研究了TOCP诱导脊髓神经元的凋亡变化,并研究了线粒体介导的OPIDN期间神经元凋亡的作用。 TUNEL分析表明母鸡脊髓中的凋亡神经元在TOCP暴露后第5天开始出现。免疫组织化学和蛋白质印迹分析显示,在服用TOCP后,细胞色素C从线粒体向细胞质易位。此外,母鸡脊髓中Bcl-2,Bcl-xl,Pro-caspase3和Pro-caspase9的水平显着降低,而Bax和裂解的PARP的水平显着升高。综上所述,这些发现表明TOCP的施用可以诱导母鸡脊髓中的神经元凋亡,这可能是由线粒体凋亡途径的激活介导的。

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