Alteration of striatal tetrahydrobiopterin in iron-induced unilateral model of Parkinson's disease.
Alteration of striatal tetrahydrobiopterin in iron-induced unilateral model of Parkinson's disease.
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DOI：
10.4196/kjpp.2014.18.2.129
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发表时间：
2014-04
期刊：
影响因子：
--
通讯作者：
Kim HG
中科院分区：
文献类型：
--
作者：
Aryal B;Lee JK;Kim HR;Kim HG
铁等过渡金属离子可对黑质纹状体多巴胺能神经元产生氧化损伤，如帕金森病（Parkinson's disease，PD），疾病进展过程中四氢生物蝶呤（tetrahydrobiopterin，BH 4）的代偿性增加可导致纹状体多巴胺能神经元变性加重。体外实验表明，BH_4直接作用于神经细胞可引起神经细胞毒性。为了阐明BH 4在体内PD发病机制中的作用，我们评估了单侧黑质内铁灌注PD大鼠模型纹状体多巴胺（DA）和BH 4的变化。黑质内铁剂注入后0.5 ~ 1d，同侧纹状体DA和BH_4水平显著升高，2 ~ 7 d持续下降。BH_4的转化率在早期高于DA。然而，在纹状体GTP-环化水解酶I mRNA的表达水平稳步增加后，铁管理。这些结果表明，黑质内铁的积累导致氧化应激的产生，其损害多巴胺能神经元并导致多巴胺能神经元中BH 4的释放增加。在体内，退变的多巴胺能神经元减少了与PD进展相关的BH 4和DA的合成和释放。基于这些数据，我们认为BH 4的增加可以在PD的早期阶段恶化疾病的进展，并且抑制BH 4的增加可能是PD治疗的策略。
It has been suggested that transition metal ions such as iron can produce an oxidative injuries to nigrostriatal dopaminergic neurons, like Parkinson's disease (PD) and subsequent compensative increase of tetrahydrobiopterin (BH4) during the disease progression induces the aggravation of dopaminergic neurodegeneration in striatum. It had been established that the direct administration of BH4 into neuron would induce the neuronal toxicity in vitro. To elucidate a role of BH4 in pathogenesis in the PD in vivo, we assessed the changes of dopamine (DA) and BH4 at striatum in unilateral intranigral iron infused PD rat model. The ipsistriatal DA and BH4 levels were significantly increased at 0.5 to 1 d and were continually depleting during 2 to 7 d after intranigral iron infusion. The turnover rate of BH4 was higher than that of DA in early phase. However, the expression level of GTP-cyclohydrolase I mRNA in striatum was steadily increased after iron administration. These results suggest that the accumulation of intranigral iron leads to generation of oxidative stress which damage to dopaminergic neurons and causes increased release of BH4 in the dopaminergic neuron. The degenerating dopaminergic neurons decrease the synthesis and release of both BH4 and DA in vivo that are relevance to the progression of PD. Based on these data, we propose that the increase of BH4 can deteriorate the disease progression in early phase of PD, and the inhibition of BH4 increase could be a strategy for PD treatment.
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DOI：
10.4196/kjpp.2012.16.5.305
发表时间：
2012-10
期刊：
The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology
影响因子：
--
作者：
Choe MA;Koo BS;An GJ;Jeon S
通讯作者：
Jeon S
影响因子：
4.2
作者：
Choi, HJ;Lee, SY;Hwang, OY
通讯作者：
Hwang, OY
影响因子：
4.7
作者：
Kim, ST;Choi, JH;Hwang, O
通讯作者：
Hwang, O
影响因子：
4.2
作者：
Lentz, SI;Kapatos, G
通讯作者：
Kapatos, G
影响因子：
4.8
作者：
Kirsch, M;Korth, HG;de Groot, H
通讯作者：
de Groot, H