ArticleJournal of biomedical science2022
Conformational alteration in glycan induces phospholipase Cβ1 activation and angiogenesis.
Article in Journal of biomedical science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- High Expression of SSEA3 and Globo H Predicts Poor Outcomes in Resected Extrahepatic Cholangiocarcinoma: A Single-Center Retrospective Cohort Study.Cancer medicine · 2026Article
- Impacts of Globo H Ceramide on Tumor Microenvironment.Advances in experimental medicine and biology · 2026Review
- Limonin induces ferroptosis in cervical squamous cell carcinoma by activating the expression of soluble epoxide hydrolase 2 protein.PloS one · 2026Article
- Globo H ceramide confers chemoresistance and poor prognosis to advanced gallbladder cancer via A2AR/cAMP/PKA pathway.Theranostics · 2026Article
- The Expression of SIRT3 in Endometrial Carcinoma and Its Effect on Promoting Apoptosis of Ishikawa Cells.Biochemical genetics · 2025Article
- Temporal vascular pattern remodeling mediated by the FHL2/sFRP2 signaling pathway in tenocytes affects tendon repair and regeneration.Experimental & molecular medicine · 2025Article
- Tumor-Associated Glycan Exploits Adenosine Receptor 2A Signaling to Facilitate Immune Evasion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Enhancing retention and quality of tissue stromal vascular fraction graft with globo H ceramide.Stem cell research & therapy · 2025Article
- Comprehensive analysis and validation of angiogenesis in vascular dementia from the perspective of diagnosis, prevention, and treatment.Frontiers in genetics · 2025Article
- Rapamycin and Niacin combination induces apoptosis and cell cycle arrest through autophagy activation on acute myeloid leukemia cells.Molecular biology reports · 2024Article
- Globo H ceramide is an independent prognostic marker for gallbladder cancer.American journal of cancer research · 2023Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundIn endothelial cells, phospholipase C (PLC) β1-activated Ca
methodsGlobo-series glycosphingolipids (GSLs), including GHCer and stage-specific embryonic antigen-3 ceramide (SSEA3Cer), were analyzed using enzyme-linked immunosorbent assay (ELISA) and Biacore for their binding with TRAX. Angiogenic activities of GSLs in human umbilical vein endothelial cells (HUVECs) were evaluated. Molecular dynamics (MD) simulation was used to study conformations of GSLs and their molecular interactions with TRAX. Fluorescence resonance energy transfer (FRET) analysis of HUVECs by confocal microscopy was used to validate the release of PLCβ1 from TRAX. Furthermore, the in vivo angiogenic activity of extracellular vesicles (EVs) containing GHCer was confirmed using subcutaneous Matrigel plug assay in mice.
resultsThe results of ELISA and Biacore analysis showed a stable complex between recombinant TRAX and synthetic GHCer with KD of 40.9 nM. In contrast, SSEA3Cer lacking a fucose residue of GHCer at the terminal showed ~ 1000-fold decrease in the binding affinity. These results were consistent with their angiogenic activities in HUVECs. The MD simulation indicated that TRAX interacted with the glycan moiety of GHCer at amino acid Q223, Q219, L142, S141, and E216. At equilibrium the stable complex maintained 4.6 ± 1.3 H-bonds. TRAX containing double mutations with Q223A and Q219A lost its ability to interact with GHCer in both MD simulation and Biacore assays. Removal of the terminal fucose from GHCer to become SSEA3Cer resulted in decreased H-bonding to 1.2 ± 1.0 by the MD simulation. Such specific H-bonding was due to the conformational alteration in the whole glycan which was affected by the presence or absence of the fucose moiety. In addition, ELISA, Biacore, and in-cell FRET assays confirmed the competition between GHCer and PLCβ1 for binding to TRAX. Furthermore, the Matrigel plug assay showed robust vessel formation in the plug containing tumor-secreted EVs or synthetic GHCer, but not in the plug with SSEA3Cer. The FRET analysis also indicated the disruption of colocalization of TRAX and PLCβ1 in cells by GHCer derived from EVs.
conclusionsOverall, the fucose residue in GHCer dictated the glycan conformation for its complexing with TRAX to release TRAX-sequestered PLCβ1, leading to Ca
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