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Reduced LRP6 expression and increase in the interaction of GSK3β with p53 contribute to podocyte apoptosis in diabetes mellitus and are prevented by green tea.
Peixoto EB, et al. J Nutr Biochem 2015. PMID 25655048
Low-density lipoprotein receptor-related protein 6 (LRP6) is WNT pathway receptor that is involved in podocyte death, adhesion and motility. ...These effects of GT were prevented by LRP6 siRNA or DKK-1. In conclusion, in DM, WNT inhibition, via LRP6, increases GSK3β-p53 and podocyte apoptosis. ...
Low-density lipoprotein receptor-related protein 6 (LRP6) is WNT pathway receptor that is involved in podocyte death, adhesion …
Parathyroid hormone signaling through low-density lipoprotein-related protein 6.
Wan M, et al. Genes Dev 2008. PMID 18981475 Free PMC article.
Here we show that binding of PTH to its receptor PTH1R induced association of LRP6, a coreceptor of Wnt, with PTH1R. The formation of the ternary complex containing PTH, PTH1R, and LRP6 promoted rapid phosphorylation of LRP6, which resulted in the recruitment of axin to LRP6, and stabilization of beta-catenin. ...In vivo studies confirmed that PTH treatment led to phosphorylation of LRP6 and an increase in amount of beta-catenin in osteoblasts with a concurrent increase in bone formation in rat. ...
Here we show that binding of PTH to its receptor PTH1R induced association of LRP6, a coreceptor of Wnt, with PTH1R. The formation of …
tPA regulates neurite outgrowth by phosphorylation of LRP5/6 in neural progenitor cells
Lee SH, et al. Mol Neurobiol 2014. PMID 23925701
The expression of Wnt and β-catenin as well as phosphorylation of LRP5 and LRP6, which has been implicated in Wnt-β-catenin signaling, was rapidly increased after tPA treatment and was decreased by tPA siRNA transfection. ...In ischemic rat brains, axon density was higher in the brains transplanted with WT NPCs than in those with tPA KO NPCs, suggesting increased axonal sprouting by NPC-derived tPA. tPA-mediated regulation of neuronal maturation in NPCs may play an important role during development and in regenerative conditions....
The expression of Wnt and β-catenin as well as phosphorylation of LRP5 and LRP6, which has been implicated in Wnt-β-catenin signaling …
REST alleviates neurotoxic prion peptide-induced synaptic abnormalities, neurofibrillary degeneration and neuronal death partially via LRP6-mediated Wnt-β-catenin signaling.
Song Z, et al. Oncotarget 2016. PMID 26919115 Free PMC article.
Overexpression of REST reduces pathological damage and abnormal biochemical alterations of neurons induced by PrP106-126 and maintains neuronal viability by stabilizing the level of pro-survival protein FOXO1 and inhibiting the permeability of the mitochondrial outer membrane, release of cytochrome c from mitochondria to cytoplasm and the activation of Capase3. ...Additionally, by overexpression or knockdown of LRP6, we further show that LRP6-mediated Wnt-β-catenin signaling partly regulates the expression of REST. ...
Overexpression of REST reduces pathological damage and abnormal biochemical alterations of neurons induced by PrP106-126 and maintains neuro …
Canonical Wnt3a modulates intracellular calcium and enhances excitatory neurotransmission in hippocampal neurons
Avila ME, et al. J Biol Chem 2010. PMID 20404321 Free PMC article.
However, the direct effect of a Wnt protein on synaptic transmission had not been demonstrated. Here we show that nanomolar concentrations of purified Wnt3a protein rapidly increase the frequency of miniature excitatory synaptic currents in embryonic rat hippocampal neurons through a mechanism involving a fast influx of calcium from the extracellular space, induction of post-translational modifications on the machinery involved in vesicle exocytosis in the presynaptic terminal leading to spontaneous Ca(2+) transients. Our results identify the Wnt3a protein and a member of its complex receptor at the membrane, the low density lipoprotein receptor-related protein 6 (LRP6) coreceptor, as key molecules in neurotransmission modulation and suggest cross-talk between canonical and Wnt/Ca(2+) signaling in central neurons....
However, the direct effect of a Wnt protein on synaptic transmission had not been demonstrated. Here we show that nanomolar concentra …
Blocking the Wnt pathway, a unifying mechanism for an angiogenic inhibitor in the serine proteinase inhibitor family
Zhang B, et al. Proc Natl Acad Sci U S A 2010. PMID 20351274 Free PMC article.
Coprecipitation and ligand binding assay showed that SERPINA3K binds to low-density lipoprotein receptor-like protein 6 (LRP6) with a K(d) of 10 nM, in the range of its physiological concentration in the retina. ...The antagonizing activity of SERPINA3K to LRP6 was further confirmed by Xenopus axis duplication assay. These results suggest that SERPINA3K is a high-affinity, endogenous antagonist of LRP6. ...
Coprecipitation and ligand binding assay showed that SERPINA3K binds to low-density lipoprotein receptor-like protein 6 (LRP6) …
Involvement of the glycogen synthase kinase-3 signaling pathway in TBI pathology and neurocognitive outcome
Dash PK, et al. PLoS One 2011. PMID 21935433 Free PMC article.
Binding of Wnt to Frizzled receptors causes the translocation of GSK-3 to the plasma membrane, where it phosphorylates and inactivates the Frizzled co-receptor lipoprotein-related protein 6 (LRP6). ...METHODOLOGY/PRINCIPAL FINDINGS: Using a rodent model, we found that TBI caused a rapid, but transient, increase in LRP6 phosphorylation that is followed by a modest decrease in ß-Catenin phosphorylation. ...
Binding of Wnt to Frizzled receptors causes the translocation of GSK-3 to the plasma membrane, where it phosphorylates and inactivates the F …
Wnt5a is associated with the differentiation of bone marrow mesenchymal stem cells in vascular calcification by connecting with different receptors
Guan S, et al. Mol Med Rep 2014. PMID 25109262
Direct co‑cultures were established by seeding two different cell types, VSMCs or calcified VSMCs, or a mixture of both at ratios of 5,000:5,000 cells/1.7 cm2 onto either gelatin‑coated 1.7‑cm2 chamber slides for immunohistochemical analysis or gelatin‑coated 75‑cm2 tissue culture flasks for protein or RNA isolation. ...Additionally, the mRNA expression levels of the genes encoding for proteins involved in the Wnt signaling proteins, Wnt5A, LRP6, Ror2, c‑Jun‑N‑terminal kinase and β‑catenin, were assessed in each group. ...
Direct co‑cultures were established by seeding two different cell types, VSMCs or calcified VSMCs, or a mixture of both at ratios of 5,000:5 …
Inhibition of LRP5/6-mediated Wnt/β-catenin signaling by Mesd attenuates hyperoxia-induced pulmonary hypertension in neonatal rats
Alapati D, et al. Pediatr Res 2013. PMID 23481549
METHODS: Newborn rat pups were randomly exposed to normoxia or hyperoxia at 90% FiO2 and injected intraperitoneally with placebo or Mesd every other day for 14 d. On day 15, phosphorylation of LRP5/6 (pLRP5/6), expression of Wnt/β-catenin target genes, cyclin D1 and Wnt-induced signaling protein-1 (WISP-1), right-ventricular systolic pressure (RVSP), right-ventricular hypertrophy (RVH), pulmonary vascular remodeling, alveolarization, and vascularization were measured. ...
METHODS: Newborn rat pups were randomly exposed to normoxia or hyperoxia at 90% FiO2 and injected intraperitoneally with placebo or M …
The role of lipid peroxidation products and oxidative stress in activation of the canonical wingless-type MMTV integration site (WNT) pathway in a rat model of diabetic retinopathy.
Zhou T, et al. Diabetologia 2011. PMID 20978740 Free PMC article.
RESULTS: Levels of phosphorylated and total LDL receptor-related protein (LRP)6, and cytosolic β-catenin, as well as transcriptional activity of T cell factor (TCF)/β-catenin were significantly increased by HNE. ...In the same diabetic rat retinas, levels of LRP6, cytosolic β-catenin and CTGF were significantly increased. NAC treatment reduced HNE and 3-nitrotyrosine levels and attenuated the upregulation of LRP6, β-catenin and CTGF in diabetic rat retina. ...
RESULTS: Levels of phosphorylated and total LDL receptor-related protein (LRP)6, and cytosolic β-catenin, as well as transcriptional …
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