title: Two-dimensional gel electrophoresis revealed antipsychotic drugs induced protein expression modulations in C6 glioma cells.
abstract: The efficacy and side effects of long-term administration of antipsychotic drugs (APDs) may be attributed to drug-induced change in protein expression in brain cells. Glial cells are non-neuronal cells that can provide nutrients and physiological support to neuronal cells. Glial cells are believed to participate in neurotransmission, neurons' early development, and guiding migration of neurons. Accumulated clinical data also indicate relationships between disturbance of glial cells' function and various psychotic diseases including schizophrenia. We used two-dimensional gel electrophoresis coupled with MALDI-TOF/TOF mass spectrometry protein identification to analyze differentially expressed proteins in haloperidol-, risperidone-, and clozapine-treated C6 glioma cells. We found that the expression of pericentrin, glial fibrillary acidic protein, Rho GDP-dissociation inhibitor 1, anionic trypsin-1, peroxiredoxin-1, and parvalbumin were regulated by each of the three APDs. Western blot analysis supported the findings. Real-time quantitative PCR detected changed transcriptions of those proteins. Protein and gene expression of N-cadherin in C6 cells were affected by haloperidol and clozapine but not risperidone. In addition, regulatory effects of clozapine on the glyceraldehyde 3-phosphate dehydrogenase gene were observed in C6 cells. This may be the first study to uncover how APD-modulated genes may cause protein expression changes and affect ARHGDIA-mediated regulation of Rho GTPase family proteins in glial cells.
authors.affiliation: Department of Research, Buddhist Tzu Chi General Hospital, Taipei Branch, New Taipei City, Taiwan, ROC. cater0656@hotmail.com
authors.forename: Mao-Liang
authors.initials: ML
authors.lastname: Chen
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003024:Clozapine / Q000494:pharmacology; D015180:Electrophoresis, Gel, Two-Dimensional; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D005910:Glioma / Q000235:genetics / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D051381:Rats; D018967:Risperidone / Q000494:pharmacology; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine; D006220:Haloperidol; D018967:Risperidone