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Open AccessArticle

Wnt Glycation Inhibits Canonical Signaling

1
Department of Biochemistry II, Jena University Hospital, Friedrich Schiller University Jena, 07743 Jena, Germany
2
Department of Cardiac Surgery, Middle German Heart Center, University Hospital Halle, Martin Luther University Halle-Wittenberg, 06120 Halle/Saale, Germany
3
Institute for Physiological Chemistry, Martin Luther University Halle-Wittenberg, 06114 Halle/Saale, Germany
*
Author to whom correspondence should be addressed.
Cells 2019, 8(11), 1320; https://doi.org/10.3390/cells8111320
Received: 5 October 2019 / Revised: 22 October 2019 / Accepted: 22 October 2019 / Published: 25 October 2019
(This article belongs to the Special Issue Glycation and Dicarbonyl Stress in Aging and Disease)
Glycation occurs as a non-enzymatic reaction between amino and thiol groups of proteins, lipids, and nucleotides with reducing sugars or α-dicarbonyl metabolites. The chemical reaction underlying is the Maillard reaction leading to the formation of a heterogeneous group of compounds named advanced glycation end products (AGEs). Deleterious effects have been observed to accompany glycation such as alterations of protein structure and function resulting in crosslinking and accumulation of insoluble protein aggregates. A substantial body of evidence associates glycation with aging. Wnt signaling plays a fundamental role in stem cell biology as well as in regeneration and repair mechanisms. Emerging evidence implicates that changes in Wnt/β-catenin pathway activity contribute to the aging process. Here, we investigated the effect of glycation of Wnt3a on its signaling activity. Methods: Glycation was induced by treatment of Wnt3a-conditioned medium (CM) with glyoxal (GO). Effects on Wnt3a signaling activity were analyzed by Topflash/Fopflash reporter gene assay, co-immunoprecipitation, and quantitative RT-PCR. Results: Our data show that GO-treatment results in glycation of Wnt3a. Glycated Wnt3a suppresses β-catenin transcriptional activity in reporter gene assays, reduced binding of β-catenin to T-cell factor 4 (TCF-4) and extenuated transcription of Wnt/β-catenin target genes. Conclusions: GO-induced glycation impairs Wnt3a signaling function. View Full-Text
Keywords: Wnt3a; β-catenin; glyoxal; methylglyoxal; glycation; advanced glycation end products; AGEs; RAGE; aging Wnt3a; β-catenin; glyoxal; methylglyoxal; glycation; advanced glycation end products; AGEs; RAGE; aging
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Ye, Z.; Mittag, S.; Schmidt, M.; Simm, A.; Horstkorte, R.; Huber, O. Wnt Glycation Inhibits Canonical Signaling. Cells 2019, 8, 1320.

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