The effects of siRNA-mediated RGS4 gene silencing on the whole genome transcription profile: implications for schizophrenia
Language English Country Sweden Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
21712773
PII: NEL320311A08
Knihovny.cz E-resources
- MeSH
- Cell Line MeSH
- Down-Regulation MeSH
- Transcription, Genetic MeSH
- Genome, Human genetics MeSH
- Histones genetics MeSH
- Cells, Cultured MeSH
- Humans MeSH
- RNA, Small Interfering pharmacology MeSH
- Microarray Analysis MeSH
- Brain-Derived Neurotrophic Factor genetics MeSH
- Neurons drug effects metabolism MeSH
- Nerve Tissue Proteins genetics MeSH
- RGS Proteins genetics MeSH
- Receptors, G-Protein-Coupled genetics MeSH
- Schizophrenia genetics MeSH
- Gene Expression Profiling MeSH
- Gene Silencing * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- ADGRG2 protein, human MeSH Browser
- GPR50 protein, human MeSH Browser
- Histones MeSH
- RNA, Small Interfering MeSH
- Brain-Derived Neurotrophic Factor MeSH
- Nerve Tissue Proteins MeSH
- RGS Proteins MeSH
- Receptors, G-Protein-Coupled MeSH
- RGS4 protein MeSH Browser
OBJECTIVE: The regulator of G-protein signaling (RGS) molecules represent a class of proteins that modulate the signaling activity of G-protein coupled receptors. Regulator of G-protein signaling 4 (RGS4) is of particular interest in schizophrenia due to reported downregulation of RGS4 transcripts in schizophrenia as well as a connection between RGS4 and a number of receptors implicated in schizophrenia. The mechanism of RGS4 involvement in the pathophysiology of this illness is not clear. METHODS: To elucidate thise role of RGS4 in pathophysiology of schizophrenia, we silenced RGS4 using siRNAs in human neuroblastoma cell lines and we studied the effects of differential RGS4 expression by microarray. RESULTS AND CONCLUSION: The cell lines with downregulated expression of RGS4 showed 67 genes with changed expression (30 underexpressed and 37 overexpressed). We have detected three subgroups of genes which might be implicated in schizophrenia pathophysiology: histone genes, which suggest epigenetic mechanisms of the disease; genes for transcription factors associated with other genes relevant to schizophrenia pathology (BDNF and DISCI1) and a heterogeneous group containing genes for G-proteins (GPR50 and GPR64) and calcium binding proteins.
Dopamine D4 receptor gene DRD4 and its association with psychiatric disorders
