A Comparative Proteomics Analysis of Rat Mitochondria from the Cerebral Cortex and Hippocampus in Response to Antipsychotic Medications

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• 作者：Baohu Ji ; Yujuan La ; Linghan Gao ; Hui Zhu ; Nan Tian ; Ming Zhang ; Yifeng Yang ; Xinzhi Zhao ; Ruqi Tang ; Gang Ma ; Jian Zhou ; Junwei Meng ; Jie Ma ; Zhao Zhang ; Huafang Li ; Guoyin Feng ; Yujiong Wang ; Lin He
• 刊名：Journal of Proteome Research
• 出版年：2009
• 出版时间：July 6, 2009
• 年：2009
• 卷：8
• 期：7
• 页码：3633-3641
• 全文大小：261K
• 年卷期：v.8,no.7(July 6, 2009)
• ISSN：1535-3907

文摘

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 (Ndufa10), 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.