A Comparative Proteomics Analysis of Rat Mitochondria from the Cerebral Cortex and Hippocampus in Response to Antipsychotic Medications
A Comparative Proteomics Analysis of Rat Mitochondria from the Cerebral Cortex and Hippocampus in Response to Antipsychotic Medications
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DOI：
10.1021/pr800876z
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发表时间：
2009-07-01
影响因子：
4.4
通讯作者：
Wan, Chunling
中科院分区：
文献类型：
--
作者：
Ji, Baohu;La, Yujuan;Wan, Chunling
越来越多的实验发现，精神病患者大脑中线粒体存在异常，提示线粒体功能障碍或脑能代谢异常可能在精神分裂症（SCZ）的病理生理中起重要作用。我们采用蛋白质组学方法，通过比较暴露于典型和非典型抗精神病药物对SD大鼠大脑皮层和海马线粒体蛋白表达的差异影响。采用二维凝胶电泳技术对氯丙嗪（CPZ）、氯氮平（CLZ）、喹硫平（QTP）组和对照组的线粒体蛋白差异表达进行分析。共有14个蛋白，其中6个属于氧化磷酸化（OXPHOS）呼吸电子传递链（ETC），它们的数量发生了显著变化，包括NADH脱氢酶（泛素）1 α亚复合物10 （Ndufa 10）、NADH脱氢酶（泛素）黄蛋白2 （Ndufv2）、NADH脱氢酶（泛素）Fe-S蛋白3 （Ndufs3）、f1 - atp酶β亚基（Atp5b）、atp酶H+转运、溶酶体、β 56/58 kDa、亚型2 （Atp6v1b2）和atp酶H+转运、V1亚基A，异构体1 （Atp6v1a1）。使用定量实时PCR （Q-RT-PCR）评估2D处理的差异蛋白的mRNA水平，我们还部分使用Western blotting来评估差异表达。我们的研究结果可能有助于解释SD大鼠以及人类对抗精神病药物反应的变化。此外，他们应该提高我们对抗精神病药物的疗效和副作用的认识，并鼓励SCZ研究的新方向。
An increasing number of experiments have found anomalies in mitochondria in the brains of psychotics, which suggests that mitochondrial dysfunction or abnormal cerebral energy metabolism might play an important role in the pathophysiology of schizophrenia (SCZ). We adopted a proteomic approach to identify the differential effects on the cerebral cortex and hippocampus mitochondrial protein expression of Sprague-Dawley (SD) rats by comparing exposure to typical and atypical antipsychotic medications. Differential mitochondrial protein expressions were assessed using two-dimensional (2D) gel electrophoresis for three groups with Chlorpromazine (CPZ), Clozapine (CLZ), quetiapine (QTP) and a control group. A total of 14 proteins, of which 6 belong to the respiratory electron transport chain (ETC) of oxidative phosphorylation (OXPHOS), showed significant changes in quantity including NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 10 (Ndufa 10), NADH dehydrogenase (ubiquinone) flavoprotein 2 (Ndufv2), NADH dehydrogenase (ubiquinone) Fe-S protein 3 (Ndufs3), F1-ATPase beta subunit (Atp5b), ATPase, H+ transporting, lysosomal, beta 56/58 kDa, isoform 2 (Atp6v1b2) and ATPase, H+ transporting, V1 subunit A, isoform 1 (Atp6v1a1). The differential proteins subjected to 2D were assessed for levels of mRNA using quantitative real time PCR (Q-RT-PCR), and we also made partial use of Western blotting for assessing differential expression. The results of our study may help to explain variations in SD rats as well as in human response to antipsychotic drugs. In addition, they should improve our understanding of both the curative effects and side effects of antipsychotics and encourage new directions in SCZ research.