Dysregulation of the protein kinase glycogen synthase kinase 3 (GSK-3) has been implicated in the development of type 2 diabetes mellitus. GSK-3 protein expression and kinase activity are elevated in diabetes, while selective GSK-3 inhibitors have shown promise as modulators of glucose metabolism and insulin sensitivity. There are two GSK-3 isoforms in mammals, GSK-3alpha and GSK-3beta. Mice en...

PURPOSE Glycogen synthase kinase-3β (GSK-3β) is a serine/threonine kinase involved in cancer development. Herein, we demonstrated the role of GSK-3β in endometrial cancer (EC) and identified new therapeutic targets. RESULTS GSK-3β was overexpressed in EC tissues, and was positively correlated with International Federation of Gynecology and Obstetrics (FIGO) staging, dedifferentiation, and myo...

Glycogen synthase kinase-3 (GSK-3) regulates multiple cellular processes, and its dysregulation is implicated in the pathogenesis of diverse diseases. In this paper we will focus on the dysfunction of GSK-3 in Alzheimer's disease and Parkinson's disease. Specifically, GSK-3 is known to interact with tau, β-amyloid (Aβ), and α-synuclein, and as such may be crucially involved in both diseases. Aβ...

The purpose of this study was to determine whether exogenous zinc prevents cardiac reperfusion injury by targeting the mitochondrial permeability transition pore (mPTP) via glycogen synthase kinase-3beta (GSK-3beta). The treatment of cardiac H9c2 cells with ZnCl2 (10 microM) in the presence of zinc ionophore pyrithione for 20 min significantly enhanced GSK-3beta phosphorylation at Ser9, indicat...

Accumulating evidence suggests that glycogen synthase kinase 3 (GSK-3) is a multifunctional kinase implicated in neuronal development, mood stabilization, and neurodegeneration. However, the synaptic actions of GSK-3 are largely unknown. In this study, we examined the impact of GSK-3 on AMPA receptor (AMPAR) channels, the major mediator of excitatory transmission, in cortical neurons. Applicati...

Neurotensin (NT), a gastrointestinal hormone, binds its receptor [neurotensin receptor (NTR)] to regulate the growth of normal and neoplastic intestinal cells; molecular mechanisms remain largely undefined. Glycogen synthase kinase-3 (GSK-3) regulates diverse cellular processes, including cell growth and apoptosis. Here, we show that NT induces the phosphorylation of GSK-3A/B in the human colon...

High NaCl activates the transcription factor nuclear factor of activated T cells 5 (NFAT5), leading to increased transcription of osmoprotective target genes. Kinases PKA, PI3K, AKT1, and p38α were known to contribute to the high NaCl-induced increase of NFAT5 activity. We now identify another kinase, GSK-3β. siRNA-mediated knock-down of GSK-3β increases NFAT5 transcriptional and transactivatin...

Chronic rhinosinusitis without nasal polyps (CRSsNP) is one of the most common otorhinolaryngologic diseases worldwide. However, the underlying mechanism remains unclear. In this study, the expression of glycogen synthase kinase 3 (GSK-3) was quantitatively evaluated in patients with CRSsNP (n = 20) and healthy controls (n = 20). The mRNA levels of GSK-3α and GSK-3β were examined by qPCR, the i...

Glycogen synthase kinase-3 (GSK-3) is linked to the pathogenesis of Alzheimer's disease (AD), senile plaques (SPs), and neurofibrillary tangles (NFTs), but the specific contributions of each of the GSK-3 α and β isoforms to mechanisms of AD have not been clarified. In this study, we sought to elucidate the role of each GSK-3α and GSK-3β using novel viral and genetic approaches. First, we develo...

RATIONALE Glycogen synthase kinase (GSK)-3β upregulates cardiac genes in bone marrow-derived mesenchymal stem cells (MSCs) in vitro. Ex vivo modification of signaling mechanisms in MSCs may improve the efficiency of cardiac cell-based therapy (CBT). OBJECTIVE To test the effect of GSK-3β on the efficiency of CBT with MSCs after myocardial infarction (MI). METHODS AND RESULTS MSCs overexpres...