Zare Zohreh, Tehrani Mohsen, Rafiei Alireza, Valadan Reza, Mohammadi Moslem
Department of Anatomical Sciences, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Department of Immunology, Molecular and Cell Biology Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Neurotoxicol Teratol. 2017 Jul;62:20-26. doi: 10.1016/j.ntt.2017.06.001. Epub 2017 Jun 8.
Glutamatergic system is involved in pathological effects of organophosphorus (OP) compounds. We aimed to determine in vivo effects of paraoxon, the bioactive metabolite of parathion, on the expression of glutamate transporters as well as Bax and Bcl2 in rat cerebral cortex. Male Wistar rats received an intraperitoneal (i.p.) injection of one of three doses of paraoxon (0.3, 0.7, or 1mg/kg) or corn oil as vehicle (1ml/kg). After 4 or 18h, cerebral cortices were dissected out and used for quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot assays to measure mRNA and protein levels, respectively. The cortical glial glutamate transporters (GLAST and GLT-1) were up-regulated in animals treated with 0.7mg/kg of paraoxon, but down-regulated in 1mg/kg group. Neuronal glutamate transporter (EAAC1) was unchanged in 0.7mg/kg treated rats, while reduced in 1mg/kg group. No significant difference was found in the mRNA and protein expression of EAAC1 in animals intoxicated with 0.3mg/kg of paraoxon. Paraoxon (1mg/kg) resulted in an up-regulation of Bax and down-regulation of Bcl2 mRNA levels in the rat cerebral cortex. These results indicate that paraoxon can differentially regulate expression of glutamate transporters at mRNA and protein levels in the cerebral cortex. Changes in the expression of glutamate transporters are closely related to paraoxon-induced seizure activity.
谷氨酸能系统参与有机磷（OP）化合物的病理作用。我们旨在确定对硫磷（对硫磷的生物活性代谢产物）对大鼠大脑皮层中谷氨酸转运体以及 Bax 和 Bcl2 表达的体内影响。雄性 Wistar 大鼠腹腔注射（i.p.）三种剂量之一的对硫磷（0.3、0.7 或 1mg/kg）或作为载体的玉米油（1ml/kg）。4 或 18 小时后，取出大脑皮层，分别用于定量逆转录聚合酶链反应（qRT-PCR）和蛋白质印迹分析，以测量 mRNA 和蛋白质水平。在接受 0.7mg/kg 对硫磷治疗的动物中，皮质胶质谷氨酸转运体（GLAST 和 GLT-1）上调，但在 1mg/kg 组中下调。在接受 0.7mg/kg 治疗的大鼠中，神经元谷氨酸转运体（EAAC1）没有变化，而在 1mg/kg 组中减少。在用 0.3mg/kg 对硫磷中毒的动物中，EAAC1 的 mRNA 和蛋白质表达没有发现显著差异。对硫磷（1mg/kg）导致大鼠大脑皮层中 Bax 上调和 Bcl2 mRNA 水平下调。这些结果表明，对硫磷可以在 mRNA 和蛋白质水平上差异调节大脑皮层中谷氨酸转运体的表达。谷氨酸转运体表达的变化与对硫磷诱导的癫痫活动密切相关。
