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谷胱甘肽和半胱氨酸对体内甲基汞诱导的纹状体多巴胺释放的保护作用。

Protective effects of glutathione and cysteine on the methylmercury-induced striatal dopamine release in vivo.

作者信息

Faro L R F, do Nascimento J L M, Campos F, Vidal L, Alfonso M, Durán R

机构信息

Departamento de Fisiologia, Centro de Ciências Biológicas, UFPA, Belém, Pará, Brasil.

出版信息

Life Sci. 2005 Jun 10;77(4):444-51. doi: 10.1016/j.lfs.2004.11.033. Epub 2005 Feb 22.

Abstract

The possible protective effects of glutathione (GSH), cysteine (CYS) and methionine (MET) on the Methylmercury (MeHg)-induced dopamine (DA) release from rat striatum were investigated using in vivo microdialysis coupled to HPLC with electrochemical detection. Intrastriatal infusion of MeHg 400 microM increased extracellular DA levels to 1941 +/- 199% in terms of basal levels. Infusion of MeHg 400 microM in GSH 400 microM pretreated animals, only increased striatal DA levels to 465 +/- 104%, in terms of basal levels, this increase being 76% lower than induced by MeHg alone. Conversely, the infusion of MeHg 400 microM after infusion of GSH 400 microM increased DA levels to 1019 +/- 96% in terms of basal levels, this increase being 47.5% lower than that observed in MeHg non-pretreated animals. The infusion of MeHg 400 microM in CYS 400 microM -pretreated animals, increased striatal DA levels to 740 +/- 149%, in terms of basal levels, this increase being 62% lower than that induced by MeHg in non-pretreated animals. The infusion of MeHg 400 microM in MET 400 microM pretreated animals increased striatal DA levels to 2011 +/- 230% in terms of basal, an increase that was not significantly different from that produced by MeHg 400 muM alone. In summary, the administration of compounds containing free -SH groups prevented the MeHg-induced DA release from rat striatum, probably due to the binding of MeHg to -SH groups. This would result in a lower metal availability to interact with -SH membrane proteins groups, which would decrease MeHg ability to interact with DA transporter.

摘要

采用体内微透析结合高效液相色谱电化学检测法,研究了谷胱甘肽(GSH)、半胱氨酸(CYS)和蛋氨酸(MET)对甲基汞(MeHg)诱导的大鼠纹状体多巴胺(DA)释放的可能保护作用。纹状体内注入400微摩尔/升的MeHg后,细胞外DA水平相对于基础水平升高至1941±199%。在预先用400微摩尔/升GSH处理的动物中注入400微摩尔/升的MeHg,纹状体DA水平相对于基础水平仅升高至465±104%,这一升高幅度比单独使用MeHg诱导的升高幅度低76%。相反,在注入400微摩尔/升GSH后再注入400微摩尔/升的MeHg,DA水平相对于基础水平升高至1019±96%,这一升高幅度比未用MeHg预处理的动物低47.5%。在预先用400微摩尔/升CYS处理的动物中注入400微摩尔/升的MeHg,纹状体DA水平相对于基础水平升高至740±149%,这一升高幅度比未预处理动物中MeHg诱导的升高幅度低62%。在预先用400微摩尔/升MET处理的动物中注入400微摩尔/升的MeHg,纹状体DA水平相对于基础水平升高至2011±230%,这一升高幅度与单独使用400微摩尔/升MeHg产生的升高幅度无显著差异。总之,给予含游离-SH基团的化合物可防止MeHg诱导的大鼠纹状体DA释放,这可能是由于MeHg与-SH基团结合。这将导致与-SH膜蛋白基团相互作用的金属可用性降低,从而降低MeHg与DA转运体相互作用的能力。

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