Disease relevance of Gsk3b

• To mimic phosphorylation-induced inhibition of GSK-3 beta activity, SB-216763 (SB), a GSK-3 beta inhibitor, was administered before ischemia or 5 min before reperfusion [1].
• Blood pressure regulates platelet-derived growth factor A-chain gene expression in vascular smooth muscle cells in vivo. An autocrine mechanism promoting hypertensive vascular hypertrophy [2].
• Pinealectomy stimulated tumor growth, LA uptake and metabolism to 13-HODE, and FA storage in hepatoma 7288CTC, whereas melatonin administration (200 microg/day) was inhibitory in vivo [3].
• These inhibitory effects of melatonin on tumor FA uptake and 13-HODE release were completely reversed by perfusion of tumors in situ with melatonin receptor antagonist S-20928, pertussis toxin, forskolin, or 8-bromo-cAMP [3].
• Advanced recipient age was associated with reduced creatinine clearance, more severe histologic injuries, including extended glomerular sclerosis, interstitial fibrosis, and vascular lesions, more pronounced cellular infiltration, and greater expression of transforming growth factor-beta and platelet-derived growth factor A and B chains [4].

High impact information on Gsk3b

• Induction of platelet-derived growth factor A-chain and c-myc gene expressions by angiotensin II in cultured rat vascular smooth muscle cells [5].
• Two classes of rat brain cDNA for this enzyme have been isolated termed GSK-3 alpha and GSK-3 beta [6].
• The nuclear expression of mitochondrial transcription factor A (Tfam), which is required for mitochondrial DNA (mtDNA) transcription and replication, must be linked to cellular energy needs [7].
• Mitochondrial transcription factor A induction by redox activation of nuclear respiratory factor 1 [7].
• Blood lipid mediator sphingosine 1-phosphate potently stimulates platelet-derived growth factor-A and -B chain expression through S1P1-Gi-Ras-MAPK-dependent induction of Kruppel-like factor 5 [8].

Chemical compound and disease context of Gsk3b

• RESULTS: Testosterone treatment resulted in an increased proteinuria as well as profound glomerulosclerosis, tubulointerstitial fibrosis, and mononuclear cell infiltration that paralleled enhanced intragraft mRNA levels of transforming growth factor-beta (TGF-beta) and platelet-derived growth factor-A and -B chain (PDGF-A and -B) [9].
• CONCLUSION: Multiglycosidorum tripterygii is superior to cyclosporine in prevention and attenuation of graft coronary arteriosclerosis and this efficacy is probably associated with the depressed expression of graft platelet-derived growth factor A mRNA in the multiglycosidorum tripterygii-treated groups [10].

Biological context of Gsk3b

• We also present the amino acid sequence of TPKI, which is identical to glycogen synthase kinase 3 beta (GSK3 beta) [11].
• Evidence for a role of glycogen synthase kinase-3 beta in rodent spermatogenesis [12].
• Thus, GSK-3 beta is expressed in germ cells entering meiosis [12].
• Glycogen synthase kinase-3 beta (GSK-3 beta) regulates cell metabolism, cell cycle, and cell fate through the phosphorylation of a diverse array of substrates [12].
• Our finding that GSK-3 beta interacted only with Ume6p but not with IME1 in a yeast 2-hybrid assay suggests that noncomplementation reflects partial divergence in substrate specificity [12].

Anatomical context of Gsk3b

• In situ hybridization (ISH) in rat testis confirmed the immunostaining pattern in leptotene and spermatids and showed a GSK-3 beta messenger RNA (mRNA) signal in some pachytene spermatocytes [12].
• Although the two GSK-3 isoforms seem to have similar properties, the difference of subcellular localization observed here suggests that TPKI/GSK-3 beta fulfills some specific function in mitochondria [13].
• Uric acid stimulates vascular smooth muscle cell proliferation by increasing platelet-derived growth factor A-chain expression [14].
• These results indicate that PUGNAc is an effective inhibitor of O-GlcNAcase in skeletal muscle and suggest that O-GlcNAc modification of proteins can induce insulin resistance in skeletal muscle independent of attenuated phosphorylation of Akt, GSK 3 alpha, GSK3 beta, and a 160-kDa protein with an Akt phosphomotif [15].
• Endoplasmic reticulum stress and trophic factor withdrawal activate distinct signaling cascades that induce glycogen synthase kinase-3 beta and a caspase-9-dependent apoptosis in cerebellar granule neurons [16].

Associations of Gsk3b with chemical compounds

• PUGNAc did not significantly alter insulin-stimulated phosphorylation of Akt (serine and threonine) or its substrates glycogen synthase kinase (GSK)3 alpha and GSK3 beta [15].
• In undifferentiated F9 cells, which are refractory to cAMP induction, transfected GSK-3 beta kinase induces a 60-fold increase in cyclic AMP response element-dependent transcription, mediated via the endogenous CREB protein [17].
• These results support a novel mechanism of tumor growth inhibition by melatonin involving a melatonin receptor-mediated suppression of cAMP levels, resulting in diminished tumor FA transport, possibly via decreased FATP function [3].
• When receptor molecules from nonlabeled PC12 cells were immunoprecipitated and then incubated in vitro with [gamma-32P]ATP and the cAMP-independent protein kinase FA/GSK-3, phosphorylation occurred predominantly on serine and to a lesser extent on threonine [18].
• These results demonstrate that the kinase that phosphorylates and inhibits the pro-survival function of MEF2D in cerebellar granule neurons is a novel lithium target distinct from GSK-3 beta [19].

Enzymatic interactions of Gsk3b

• In addition, 4R did not enhance total phospho-ERK-1/2 but increased the amount of total Akt/PKB phosphorylated on the activation site and of glycogen synthase kinase 3-beta phosphorylated on the inhibitory site [20].

Regulatory relationships of Gsk3b

• Erythropoietin affords additional cardioprotection to preconditioned hearts by enhanced phosphorylation of glycogen synthase kinase-3 beta [1].
• METHODS AND RESULTS: First, the IGF-1 induced signal transduction leading to GSK-3beta in neonatal rat cardiomyocytes was examined [21].

Other interactions of Gsk3b

• In fact, we found that beta-catenin was up-regulated, escaping the glycogen synthase kinase-3 beta (GSK-3 beta) control, through unclear mechanisms [22].
• HO-3073 enhanced the ischaemia-reperfusion-triggered phosphorylation of Akt-1 (activation) and glycogen synthase kinase-3 beta (inactivation) as evidenced by Western blot analysis [23].
• Platelet-derived growth factor-A chain mRNA levels increased in day 3 allografts and in syngeneic LEW grafts, while PDGF-B chain mRNA levels showed no significant changes with transplantation [24].
• Transcripts for transforming growth factor alpha, platelet-derived growth factor A-chain, and platelet-derived growth factor B-chain were not detected [25].
• The aim of this study was to determine whether erythropoietin (EPO) affords additional cardioprotection to the preconditioned myocardium by enhanced phosphorylation of Akt, STAT3, or glycogen synthase kinase-3beta (GSK-3 beta) [1].

Analytical, diagnostic and therapeutic context of Gsk3b

• Immunoprecipitation with a mixture of the two peptide antibodies allows for the detection and estimation of the total kinase FA/GSK3 activity in cellular extracts, whereas the alpha-peptide antibody specifically detects and measures the GSK3-alpha isoform [26].
• Results from immunoelectron microscopy and subcellular fractionation revealed that one isoform, tau protein kinase I/GSK-3 beta (TPKI/GSK-3 beta), was present in mitochondria, but GSK-3 alpha was not [13].
• The additive effects of PC and EPO on infarct size were mirrored by their effects on the level of phosphorylated GSK-3 beta at 5 min after reperfusion but not their effects on the level of phospho-Akt or phospho-STAT3 [1].
• Furthermore, the expression of platelet-derived growth factor A- and B-chain proteins was analysed by enzyme-linked immunosorbent assay and immunohistochemistry [27].
• Histological evaluations of rejection and coronary arteriosclerosis, as well as Northern blot analysis on graft platelet-derived growth factor A mRNA expression were made 60 days after transplantation [10].

References