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氨己烯酸抑制癫痫易感沙鼠海马中的磷酸吡哆醛 -5'-磷酸氧化酶,而非磷酸吡哆醛激酶。

Vigabatrin inhibits pyridoxine-5'-phosphate oxidase, not pyridoxal kinase in the hippocampus of seizure prone gerbils.

作者信息

An Sung-Jin, Park Seung-Kook, Hwang In Koo, Choi Soo-Young, Kwon Oh-Shin, Won Moo Ho, Kang Tae-Cheon

机构信息

Department of Anatomy, College of Medicine, Hallym University, Kangwon-Do 200-702, Chunchon, South Korea.

出版信息

Neurochem Int. 2004 Feb;44(3):133-7. doi: 10.1016/s0197-0186(03)00135-9.

DOI:10.1016/s0197-0186(03)00135-9
PMID:14568555
Abstract

To identify the effects of vigabatrin (VGB) on the metabolism of pyridoxal 5'-phosphate (PLP) in the seizure prone gerbil hippocampus, we conducted a chronological and comparative analysis of pyridoxal kinase (PLK) and pyridoxine-5'-phosphate oxidase (PNP oxidase) expression. In the VGB treated animals, PNP oxidase immunoreactivity was reduced, although the distribution and immunodensity of PLK were unaltered, as compared with control animals. In a Western blot study, the densities of PNP oxidase immunoreactivities in VGB treated animals were found to have decreased significantly. However, no differences in PLK immunoreactive bands were observed in controls or in VGB treated animals. By enzyme activity assay, and in contrast to PLK, the specific activity of PNP oxidase in the VGB treated gerbils was significantly reduced. In conclusion, the present data presents a piece of in vivo evidence that supports the anti-epileptic effects mediated by pyridoxamine-5'-phosphate (PMP) metabolism, and which may be helpful in the development of an anti-epileptic drug.

摘要

为了确定氨己烯酸(VGB)对癫痫易感沙鼠海马中磷酸吡哆醛(PLP)代谢的影响,我们对吡哆醛激酶(PLK)和磷酸吡哆醛氧化酶(PNP氧化酶)的表达进行了时间顺序和比较分析。与对照动物相比,在接受VGB治疗的动物中,PNP氧化酶免疫反应性降低,尽管PLK的分布和免疫密度未改变。在蛋白质印迹研究中,发现接受VGB治疗的动物中PNP氧化酶免疫反应性的密度显著降低。然而,在对照动物或接受VGB治疗的动物中未观察到PLK免疫反应条带的差异。通过酶活性测定,与PLK相反,接受VGB治疗的沙鼠中PNP氧化酶的比活性显著降低。总之,目前的数据提供了一条体内证据,支持由磷酸吡哆胺-5'-磷酸(PMP)代谢介导的抗癫痫作用,这可能有助于抗癫痫药物的开发。

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