Antipsychotic drug-associated gene-miRNA interaction in T-lymphocytes.
Antipsychotic drugs (APDs) can have a profound effect on the human body that extends well beyond our understanding of their neuropsychopharmacology. Some of these effects manifest themselves in peripheral blood lymphocytes, and in some cases, particularly in clozapine treatment, result in serious complications. To better understand the molecular biology of APD action in lymphocytes, we investigated the influence of chlorpromazine, haloperidol and clozapine in vitro, by microarray-based gene and microRNA (miRNA) expression analysis. JM-Jurkat T-lymphocytes were cultured in the presence of the APDs or vehicle alone over 2 wk to model the early effects of APDs on expression. Interestingly both haloperidol and clozapine appear to regulate the expression of a large number of genes. Functional analysis of APD-associated differential expression revealed changes in genes related to oxidative stress, metabolic disease and surprisingly also implicated pathways and biological processes associated with neurological disease consistent with current understanding of the activity of APDs. We also identified miRNA-mRNA interaction associated with metabolic pathways and cell death/survival, all which could have relevance to known side effects of APDs. These results indicate that APDs have a significant effect on expression in peripheral tissue that relate to both known mechanisms as well as poorly characterized side effects.
School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, The University of Newcastle, NSW, Australia.
Erin
E
Gardiner
School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, The University of Newcastle, NSW, Australia.
Adam
A
Carroll
School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, The University of Newcastle, NSW, Australia.
Paul A
PA
Tooney
School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, The University of Newcastle, NSW, Australia.
Murray J
MJ
Cairns
D014150:Antipsychotic Agents / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002746:Chlorpromazine / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D035683:MicroRNAs / Q000378:metabolism*; D046228:Microarray Analysis; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*
D014150:Antipsychotic Agents; D035683:MicroRNAs; D012333:RNA, Messenger; D003024:Clozapine; D006220:Haloperidol; D002746:Chlorpromazine