Common Antipsychotics Research By Proteomic Method

Schizophrenia is a mental disorder that affects approximately 1 % of the population. In the present, it is recognized that schizophrenia caused by the interaction of numerous minor effect genes and the influence of the environment. Proteins are the functional translation of the genomic information and the final results from the multiple factors interactively effecting on the disease. Hence, a better way to elucidate the eiology of schizophrenia is underlying the technology from the proteins level.Plasma is a good experimental sample, which is easy to be collected and can be analyzed at the time of presentation and throughout the course of the disease. In this study,we used proteomic method to screen for plasma protein alternations of the antipsychotic-treated schizophrenia patients. Plasma protein expression profile was studied before and after Risperidone-treatment in 10 first-onset schizophrenia patients at baseline and after 4 weeks of treatment. We found that the expression levels of Apolipoprotein A-I, Transthyretin and Retinol Binding Protein were up-regulated significantly, whileα1-antitrypsin showed a significant down-regulation after 4-week risperidone-treatment. This study is an independent validation for the previous studies by our team made. Combined with previous studies, we considered that (a) the altered expression level of acute phase protein indicated that an altered inflammatory response system in schizophrenia; (b) an alternation of ApoA-I is related with the pathologic processes of schizophrenia; (c) the altered-regulation of TTR and RBP which associate with VA metabolism could be not caused by antipsychotic-treatment, and VA metabolism pathway may be linked with the pathophysiology of schizophrenia.Antipsychotics are still the main treatment to alleviate the pain of schizophrenia patients. Most drugs are metabolized mainly in the liver, and drug-induced liver injury is a potential complication of nearly every medication that is prescribed. A proteomics study was conducted to provide valuable information regarding biochemical consequences by antipsychotics. In present study, rats were treated with chlorpromazine, clozapine and seroquel, respectively for 34 days. Proteins extracted from the liver were analyzed by 2-DE technology, and 123 distinct spots including 80 different proteins were identified by MALDI-TOF MS on the basis of peptide mass fingerprinting. Compared with the non-treated group, 215 protein spots were taken into account, 33 spots corresponding to 26 proteins were found with altered levels in the antipsychotic-treated groups, especially 3-mercaptopyruvate sulfurtransferase, peroxiredoxin-2, cytochrome b5, cytokeratin-18, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, 3-oxo-5-beta-steroid 4-dehydrogenase and 3-alpha-hydroxysteroid dehydrogenase, which were altered extremely(p value<0.01). Our results suggest that antipsychotic could induce oxidative stress in the rat liver, and abnormal bile acid metabolism could be a signal of liver injury by antipsychotics. Combined with the recent studies, we propose hypothesis that some identical change of oxidative stress could exist in both liver cells and neurocytes. Although the exact molecular mechanism of antipsychotic activities in the liver is still unknown, our results provide valuable information for antipsychotics choice/screening.