Rabbit Anti-Human GSK3B Polyclonal antibody

Glycogen synthase kinase 3 beta (Gsk3b) acts as a negative modulator in endothelial cells through the Wnt/beta-catenin/PI3K/AKT/Gsk3b axis in cancer- induced angiogenesis. However, the function of Gsk3b during embryonic angiogenesis remains unclear. Here, either gsk3b knockdown by morpholino or Gsk3b loss of activity by LiCl treatment had serious phenotypic consequences, such as defects in the positioning and patterning of intersegmental blood vessels and reduction of vegfaa121 and vegfaa165 transcripts. In embryos treated with the phosphatidylinositol 3-kinase inhibitor, angiogenesis was severely inhibited, along with reduced Wnt, phosphorylated AKT and phosphorylated Gsk3b, suggesting that the remaining Gsk3b in somites could still degrade beta-catenin, resulting in decreased vascular endothelial growth factor Aa(VegfAa) expression. However, in Gsk3b-mRNA-overexpressed embryos, intersegmental vessels ectopically sprouted by the increase in phosphorylated-Gsk3b which prevented the degradation of beta-catenin and promoted the increase in phosphorylated AKT activity, thus increasing VegfAa expression in somites. Interestingly, the Gsk3b-dependent cross-talk between PI3K/AKT and Wnt/beta-catenin suggests that Wnt/beta-catenin and PI3K/AKT interaction controls embryonic angiogenesis by a positive feedback loop rather than a hierarchical framework such as that found in cancer-induced angiogenesis. Thus, both active and inactive forms of Gsk3b mediate the cooperative signaling between Wnt/beta-catenin and PI3K/AKT to control VegfAa expression in somites during angiogenesis in zebrafish embryos.

Cognitive deficits are common in patients with bipolar disorder (BD) in remission and may be associated with glycogen synthase kinase-3 (GSK-3) activity, which is inhibited by lithium. GSK-3 may be a relevant treatment target for interventions tailored at cognitive disturbances in BD but the relation between GSK-3 activity, cognition and lithium treatment is unknown. We therefore investigated the possible association between GSK-3 activity and cognition and whether lithium treatment moderates this association in patients with BD. In a prospective 6-12 month follow-up study, GSK- 313 activity in peripheral blood mononuclear cells was measured concurrently with cognitive performance assessed using a comprehensive test battery in 27 patients with BD-I in early and late remission following a manic or mixed episode. The GSK-313 activity, measured as serine-9 phosphorylated GSK-313 (pGSK-3(3) and the GSK-313 ratio (serine-9-pGSK-313 /total GSK-3(3), was negatively associated with sustained attention (p = 0.009 and p = 0.042, respectively), but not with other cognitive domains or global cognition. A crossover interaction between lithium treatment and the GSK activity was observed, indicating that lower pGSK-313 levels (p = 0.015) and GSK ratio (p = 0.010) were associated with better global cognition in lithium users whereas the opposite association was observed in non-lithium treated patients. Findings were not statistically significant after Bonferroni correction. In conclusion, cognitive functioning may be associated with GSK-3 activity in patients with BD-I and lithium treatment may modulate this relationship. Future studies in larger sample sizes are warranted to confirm these associations. (C) 2018 Elsevier B.V. and ECNP. All rights reserved.