Identification of a Novel Gene with RING-H2 Finger Motif Induced after Chronic Antidepressant Treatment in Rat Brain

doi:10.1006/bbrc.2000.3773

Biochemical and Biophysical Research Communications

Volume 278, Issue 1, 11 November 2000, Pages 150-157

https://doi.org/10.1006/bbrc.2000.3773 Get rights and content

Abstract

Previously, we have identified 200 cDNA fragments as antidepressant related genes/ESTs. In this study, using these cDNAs, we developed our original cDNA microarray for rapid secondary screening of candidate genes as the novel therapeutic targets. With this microarray, we found that the expression of a novel gene, ADRG34, was significantly increased in rat hippocampus which had been chronically treated with a selective serotonin reuptake inhibitor antidepressant, sertraline. RT-PCR analysis also demonstrated the induction of ADRG34 at mRNA levels in rat hippocampus and the frontal cortex. This cDNA encoded 685 amino acid residues containing a RING-H2 finger motif at the carboxy-terminal. Sequence analysis of ADRG34 with the EMBL/GenBank database showed significant homology to mouse and human kf-1 gene. Our data suggest that ADRG34, a possible rat homologue of kf-1, may be one of the common functional molecules induced after chronic antidepressant treatment.

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Serotonin (5-HT) is a key modulator of numerous physiological processes and behaviors, such as mood, anxiety and sexual behaviors (Jacobs and Azmitia, 1992; Lucki, 1998), therefore, many genes are regulated by the serotonergic system (Sillaber et al., 2008; Park et al., 2012). Antidepressant-related gene 34 (Adgr34), a RING finger protein, is regulated by the serotonergic system (Yamada et al., 2000). Adrg34 gene expression is induced in the rat hippocampus and the frontal cortex by disruption of the serotonergic system.
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Sertraline was dissolved in saline containing 0.45% cyclodextrin. According to our previous publications, drugs or vehicles were administered at a dose of 10 ml/kg of body weight (Yamada et al., 2000, 2001, 2002). To minimize the test-order effects as possible, we performed the behavioral tests starting from the less stressful test.
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Immunoprecipitated complexes were eluted from the beads using SDS sample buffer prior to SDS–PAGE and immunoblotting. Since Kf-1 is associated with a pathophysiology of Alzheimer’s disease [1] or alleviation of depression [2–4], the expression of the Kf-1 protein was investigated in rat brain by immunohistochemistry. Using specific anti-Kf-1 antibody, Kf-1 appeared in the pyramidal cell layer of the hippocampal region and located in the neuron-specific nuclear protein (NeuN)-positive neurons (Fig. 1A, first row).
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^☆: The GenBank accession number for the nucleotide sequence is AF306394.

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Regular ArticleIdentification of a Novel Gene with RING-H2 Finger Motif Induced after Chronic Antidepressant Treatment in Rat Brain☆

Abstract

Biol. Psychiatry

Neuroscience

Brain Res. Mol. Brain Res.

Neuropharmacology

Prog. Neuropsychopharmacol. Biol. Psychiatry

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.

Gene

J. Biol. Chem.

Genomics

J. Biol. Chem.

Am. J. Psychiatry

Psychopharmacology

Regular Article
Identification of a Novel Gene with RING-H2 Finger Motif Induced after Chronic Antidepressant Treatment in Rat Brain☆