Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.11.26 (
GSK
)
6,788
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Lithium and GADL1 regulate glycogen synthase kinase-3 activity to modulate KCTD12 expression. 3131 80
