MPTP decreases MT-I mRNA in mouse striatum.
MPTP decreases MT-I mRNA in mouse striatum.
复制标题
MPTP 降低小鼠纹状体中的 MT-I mRNA。
DOI：
10.1023/a:1007564126478
复制
发表时间：
2000
影响因子：
4.4
通讯作者：
Ebadi,M
中科院分区：
文献类型：
--
作者：
Rojas,P;Rojas-Castañeda,J;Vigueras,RM;Habeebu,SS;Rojas,C;Ríos,C;Ebadi,M
1-甲基-4-苯基-1，2，3，6-四氢吡啶(MPTP)是一种在人类和非人类灵长类动物中诱导帕金森综合征的药物。自由基被认为与其作用机制有关。最近，金属硫蛋白被认为是一种自由基清除剂。在本工作中，我们研究了MPTP神经毒性对脑金属硫蛋白-I(MT-I)基因表达的影响。雄性C-57黑鼠每日ip MPTP 30 mg/kg，连续3~5天。末次注射MPTP后7d，所有动物均被颈椎脱位处死。快速取出脑组织并立即冰冻，用MT-I基因探针进行定量原位杂交。纹状体是已知对MPTP氧化应激高度易感和敏感的区域，在最后一次注射MPTP后，纹状体的MT-IMRNA含量分别下降了30%(3天)和39%(5天)。这些结果提示在MPTP神经毒性中MT-I基因表达减少。提示MPTP可降低纹状体中的抗氧化剂和自由基清除剂MT，从而使神经毒素对纹状体产生最大的氧化损伤。
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a drug that induces parkinsonism in humans and non-human primates. Free radicals are thought to be involved in its mechanism of action. Recently, metallothionein has been proposed to play a role as a scavenger of free radicals. In the present work, we studied the effect of MPTP neurotoxicity on brain metallothionein-I (MT-I) mRNA expression. Male C-57 black mice were treated with MPTP (30 mg/kg, i.p., daily) for 3 or 5 days. All animals were killed by cervical dislocation 7 days after the last MPTP dose. The brains were removed quickly and immediately frozen, and quantitative in situ hybridization was performed using MT-I cDNA probe. MT-I mRNA content in striatum, a region which is known to be highly predisposed and sensitive to MPTP-induced oxidative stress, decreased by 30% (3 days) and 39% (5 days) respectively, after the last MPTP administration. These results suggest that MT-I gene expression is decreased in MPTP neurotoxicity. It is suggested that the reduction of MT, an anti-oxidant and a free radical scavenger, in the striatum by MPTP enables the neurotoxin to exert maximal oxidative damage to the striatum.