OBJECTIVE Alteration in endoplasmic reticulum (ER) stress in diabetic hearts and its effect on cytoprotective signaling are unclear. Here, we examine the hypothesis that ER stress in diabetic hearts impairs phospho-glycogen synthase kinase (GSK)-3beta-mediated suppression of mitochondrial permeability transition pore (mPTP) opening, compromising myocardial response to cytoprotective signaling. ...

Growth hormone (GH) regulates transcription factors associated with c-fos, including C/EBPbeta. Two forms of C/EBPbeta, liver-activating protein (LAP) and liver inhibitory protein (LIP), are dephosphorylated in GH-treated 3T3-F442A fibroblasts. GH-induced dephosphorylation of LAP and LIP is reduced when cells are preincubated with phosphatidylinositol 3'-kinase (PI3K) inhibitors. GH activates A...

Glycogen synthase kinase-3 beta (GSK-3 beta/zeste-white-3/shaggy) is a negative regulator of the wnt signaling pathway which plays a central role in the development of invertebrates and vertebrates; loss of function and dominant negative mutations in GSK-3 beta lead to activation of the wnt pathway in Drosophila and Xenopus. We now provide evidence that lithium activates downstream components o...

Based on extensive preclinical data, glycogen synthase kinase-3 (GSK-3) has been proposed to be a viable drug target for a wide variety of disease states, ranging from diabetes to bipolar disorder. Since these new drugs, which will be more powerful GSK-3 inhibitors than lithium, may potentially be given to women of childbearing potential, and since it has controversially been suggested that lit...

Glycogen synthase kinase-3 (GSK-3) mediates epidermal growth factor, insulin and Wnt signals to various downstream events such as glycogen metabolism, gene expression, proliferation and differentiation. We have isolated here a GSK-3β-interacting protein from a rat brain cDNA library using a yeast twohybrid method. This protein consists of 832 amino acids and possesses Regulators of G protein Si...

Objective This study aimed to investigate whether the nonselective A2 adenosine receptor agonist NECA induces cardioprotection against myocardial ischemia/reperfusion (I/R) injury via glycogen synthase kinase 3β (GSK-3β) and the mitochondrial permeability transition pore (mPTP) through inhibition of endoplasmic reticulum stress (ERS). Methods and Results H9c2 cells were exposed to H2O2 for 20...

GSK-3 is a serine/threonine kinase involved in a diverse range of cellular processes. GSK-3 exists in two isoforms, GSK-3α and GSK-3β, which possess some functional redundancy but also play distinct roles depending on developmental and cellular context. In this article, we found that GSK-3 actively promoted cell growth and survival in melanoma cells, and blocking this activity with small-molecu...

Editor’s key points † Ketamine increased neuroapoptosis in neonatal rat pups, which correlated with decreased GSK-3b phosphorylation. † This suggests involvement of this cell survival signalling pathway in anaesthetic neurotoxicity. † Co-administration of lithium mitigated ketamine-induced neurotoxicity and reduction in GSK-3b phosphorylation, providing a potential approach to neuroprotection. ...

Glycogen synthase kinase-3 (GSK-3) is ubiquitously expressed and unusually active in resting, non-stimulated cells. In mammals, at least three proteins (α, β1, and β2), generated from two different genes, gsk-3α and gsk-3β, are widely expressed at both the RNA and protein levels although some tissues show preferential expression of some of the three proteins. Control of GSK-3 activity occurs by...

The terrestrial anuran Rana sylvatica tolerates extended periods of whole-body freezing during the winter. Freezing survival is facilitated by extensive glycogen hydrolysis and distribution of high concentrations of the cryoprotectant glucose into blood and all tissues. As glycogenesis is both an energy-expensive process and counter-productive to maintaining sustained high cryoprotectant levels...