Journal
MOLECULAR BRAIN RESEARCH
Volume 124, Issue 1, Pages 70-78Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.molbrainres.2004.02.010
Keywords
5-HT2C receptor; RNA editing; dsRNA adenosine deaminase; ADAR; interferon; depression
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Members of the ADAR (adenosine deaminases acting on RNA) gene family are involved in one type of RNA editing that converts adenosine residues to inosine. The A-to-l editing of serotonin receptor Subtype 2C (5-HT2CR) mRNA leads to replacement of three amino acid residues located within the intracellular loop II domain, resulting in dramatic alterations in G-protein coupling functions of the receptor. It has been speculated that RNA editing may play a role in several pharmacological and behavioral processes where the serotonergic plasticity is mediated through 5-HT2CR. Interferon-alpha (IFN-alpha) often causes severe depression in patients treated for chronic viral hepatitis and certain malignancies. In this study, we examined the effects of IFN-alpha on RNA editing in human glioblastoma cell lines, which express 5-HT2CR mRNAs. ADAR1 expression and the pattern of the 5-HT2CR mRNA editing rapidly changed in response to IFN-alpha, leading to the dominant expression of the 5-HT2C-R-VSI isoform predicted to have reduced G-protein coupling functions. Our results Support the hypothesis that 5-HT2CR mRNA editing has causative relevance in the pathophysiology of depression associated with cytokine therapy. (C) 2004 Elsevier B.V. All rights reserved.
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