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Lithium and GADL1 regulate glycogen synthase kinase-3 activity to modulate KCTD12 expression
Potassium channel tetramerization domain containing 12 (KCTD12), the auxiliary GABA(B) receptor subunit, is identified as a susceptibility gene for bipolar I (BPI) disorder in the Han Chinese population. Moreover, the single-nucleotide polymorphism (SNP) rs17026688 in glutamate decarboxylase–like pr...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6635502/ https://www.ncbi.nlm.nih.gov/pubmed/31311980 http://dx.doi.org/10.1038/s41598-019-46655-1 |
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author | Wu, Tai-Na Chen, Chih-Ken Lee, Chau-Shoun Wu, Bo-Jian Sun, Hsiao-Ju Chang, Chieh-Hsing Chen, Chun-Ying Wu, Lawrence Shih-Hsin Cheng, Andrew Tai-Ann |
author_facet | Wu, Tai-Na Chen, Chih-Ken Lee, Chau-Shoun Wu, Bo-Jian Sun, Hsiao-Ju Chang, Chieh-Hsing Chen, Chun-Ying Wu, Lawrence Shih-Hsin Cheng, Andrew Tai-Ann |
author_sort | Wu, Tai-Na |
collection | PubMed |
description | Potassium channel tetramerization domain containing 12 (KCTD12), the auxiliary GABA(B) receptor subunit, is identified as a susceptibility gene for bipolar I (BPI) disorder in the Han Chinese population. Moreover, the single-nucleotide polymorphism (SNP) rs17026688 in glutamate decarboxylase–like protein 1 (GADL1) is shown to be associated with lithium response in Han Chinese BPI patients. In this study, we demonstrated for the first time the relationship among lithium, GADL1, and KCTD12. In circulating CD11b(+) macrophage cells, BPI patients showed a significantly higher percentage of KCTD12 expression than healthy controls. Among BPI patients, carriers of the ‘T’ allele (i.e., CT or TT) at site rs17026688 were found to secrete lower amounts of GADL1 but higher amounts of GABA b receptor 2 (GABBR2) in the plasma. In human SH-SY5Y neuroblastoma cells, lithium treatment increased the percentage of KCTD12 expression. Through inhibition of glycogen synthase kinase-3 (GSK-3), lithium induced cyclic AMP-response element binding protein (CREB)–mediated KCTD12 promoter activation. On the other hand, GADL1 overexpression enhanced GSK-3 activation and inhibited KCTD12 expression. We found that lithium induced, whereas GADL1 inhibited, KCTD12 expression. These findings suggested that KCTD12 may be an important gene with respect to neuron excitability and lithium response in BPI patients. Therefore, targeting GSK-3 activity and/or KCTD12 expression may constitute a possible therapeutic strategy for treating patients with BPI disorder. |
format | Online Article Text |
id | pubmed-6635502 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-66355022019-07-24 Lithium and GADL1 regulate glycogen synthase kinase-3 activity to modulate KCTD12 expression Wu, Tai-Na Chen, Chih-Ken Lee, Chau-Shoun Wu, Bo-Jian Sun, Hsiao-Ju Chang, Chieh-Hsing Chen, Chun-Ying Wu, Lawrence Shih-Hsin Cheng, Andrew Tai-Ann Sci Rep Article Potassium channel tetramerization domain containing 12 (KCTD12), the auxiliary GABA(B) receptor subunit, is identified as a susceptibility gene for bipolar I (BPI) disorder in the Han Chinese population. Moreover, the single-nucleotide polymorphism (SNP) rs17026688 in glutamate decarboxylase–like protein 1 (GADL1) is shown to be associated with lithium response in Han Chinese BPI patients. In this study, we demonstrated for the first time the relationship among lithium, GADL1, and KCTD12. In circulating CD11b(+) macrophage cells, BPI patients showed a significantly higher percentage of KCTD12 expression than healthy controls. Among BPI patients, carriers of the ‘T’ allele (i.e., CT or TT) at site rs17026688 were found to secrete lower amounts of GADL1 but higher amounts of GABA b receptor 2 (GABBR2) in the plasma. In human SH-SY5Y neuroblastoma cells, lithium treatment increased the percentage of KCTD12 expression. Through inhibition of glycogen synthase kinase-3 (GSK-3), lithium induced cyclic AMP-response element binding protein (CREB)–mediated KCTD12 promoter activation. On the other hand, GADL1 overexpression enhanced GSK-3 activation and inhibited KCTD12 expression. We found that lithium induced, whereas GADL1 inhibited, KCTD12 expression. These findings suggested that KCTD12 may be an important gene with respect to neuron excitability and lithium response in BPI patients. Therefore, targeting GSK-3 activity and/or KCTD12 expression may constitute a possible therapeutic strategy for treating patients with BPI disorder. Nature Publishing Group UK 2019-07-16 /pmc/articles/PMC6635502/ /pubmed/31311980 http://dx.doi.org/10.1038/s41598-019-46655-1 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Wu, Tai-Na Chen, Chih-Ken Lee, Chau-Shoun Wu, Bo-Jian Sun, Hsiao-Ju Chang, Chieh-Hsing Chen, Chun-Ying Wu, Lawrence Shih-Hsin Cheng, Andrew Tai-Ann Lithium and GADL1 regulate glycogen synthase kinase-3 activity to modulate KCTD12 expression |
title | Lithium and GADL1 regulate glycogen synthase kinase-3 activity to modulate KCTD12 expression |
title_full | Lithium and GADL1 regulate glycogen synthase kinase-3 activity to modulate KCTD12 expression |
title_fullStr | Lithium and GADL1 regulate glycogen synthase kinase-3 activity to modulate KCTD12 expression |
title_full_unstemmed | Lithium and GADL1 regulate glycogen synthase kinase-3 activity to modulate KCTD12 expression |
title_short | Lithium and GADL1 regulate glycogen synthase kinase-3 activity to modulate KCTD12 expression |
title_sort | lithium and gadl1 regulate glycogen synthase kinase-3 activity to modulate kctd12 expression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6635502/ https://www.ncbi.nlm.nih.gov/pubmed/31311980 http://dx.doi.org/10.1038/s41598-019-46655-1 |
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