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KMID : 0389420100180030229
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Korean Journal of Stress Research
2010 Volume.18 No. 3 p.229 ~ p.235
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Suppressive Effect of Clozapine through Regulation of Chemokine (C-C motif) Ligand Genes in SH-SY5Y Human Neuroblastoma Cells
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Park Hae-Jeong
Cho Ah-Rang
Park Jin-Kyung
Kang Won-Sub
Kim Jong-Woo
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Abstract
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Clozapine, an atypical antipsychotic agent, has proven to be effective in the treatment of refractory schizophrenia. As the idiosyncratic clozapine-induced adverse effects such as dyslipidemia and agranulocytosis occur in 0.5∼2% of the treated patients, the use of clozapine has been limited. In this study, we assessed the patterns of gene regulation by clozapine (10?M, 24 h) in SH-SY5Y human neuroblastoma cells through microarray analysis. Clozapine upregulated the expressions of 165 genes, and downregulated the expressions of 305 genes. Of these genes, clozapine potently increased the level of chemokine (C-C motif) ligand 3 gene (CCL3, 15.596-fold) and decreased the level of retinoic acid early transcript 1E (RAET1E, 0.171-fold). Both of these genes belong to the category of immune response-related genes. We also found the changes of the expressions of immune response-related genes were most remarkable. Especially, clozapine increased the levels of chemokine genes, such as CCL3 (also known as MIP-1?), CCL2 (also known as MCP-1), and chemokine (C-C motif) receptor 3 (CCR3). This result may contribute to understanding of adverse effects of clozapine.
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KEYWORD
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Clozapine, Microarray, Immune response-related gene, SH-SY5Y
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