Long-chain bases are present in the oral cavity. Previously we determined that sphingosine, dihydrosphingosine, and phytosphingosine have potent antimicrobial activity against oral pathogens. Here, we determined the cytotoxicities of long-chain bases for oral cells, an important step in considering their potential as antimicrobial agents for oral infections. This information would clearly help in establishing prophylactic or therapeutic doses. To assess this, human oral gingival epithelial (GE) keratinocytes, oral gingival fibroblasts (GF), and dendritic cells (DC) were exposed to 10.0-640.0 μM long-chain bases and glycerol monolaurate (GML). The effects of long-chain bases on cell metabolism (conversion of resazurin to resorufin), membrane permeability (uptake of propidium iodide or SYTOX-Green), release of cellular contents (LDH), and cell morphology (confocal microscopy) were all determined. GE keratinocytes were more resistant to long-chain bases as compared to GF and DC, which were more susceptible. For DC, 0.2-10.0 μM long-chain bases and GML were not cytotoxic; 40.0-80.0 μM long-chain bases, but not GML, were cytotoxic; and 80.0 μM long-chain bases induced cellular damage and death in less than 20 min. The LD50 of long-chain bases for GE keratinocytes, GF, and DC were considerably higher than their minimal inhibitory concentrations for oral pathogens, a finding important to pursuing their future potential in treating periodontal and oral infections.
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http://dx.doi.org/10.1016/j.toxlet.2015.05.012 | DOI Listing |
J Pharm Biomed Anal
December 2024
Institute of Biomolecular Chemistry ICB, CNR, Traversa La Crucca 3, Regione Baldinca, Li Punti, Sassari 07100, Italy. Electronic address:
N-(3-hydroxyacyl)glycines are compounds of remarkable interest due to their biogenic origin and bioactivity and as precursors of the corresponding 3-acyloxy derivatives which represent an important class of bioactive products of bacterial origin. Commendamide [N-(3-hydroxypalmitoyl)glycine] (1) is a gut microbiota-derived bioactive metabolite that is structurally like endogenous long-chain N-acyl-amino acids belonging to the endocannabinoidome, a complex lipid signaling system involved in several aspects of mammalian physiology and pathology. Thanks to this structural similarity, this compound and its analogues, like the N-(3-hydroxymyristoyl)glycine 2, exert a remarkable bioactivity in mammals, for instance, through activation of G-protein-coupled receptors (GPCRs).
View Article and Find Full Text PDFMetab Eng
January 2025
Department of Life Science, Chung-Ang University, Seoul, 06974, South Korea. Electronic address:
Sphingolipids are vital membrane components in in mammalian cells, plants, and various microbes. We aimed to explore and exploit the sphingolipid biosynthesis pathways in an oleaginous and dimorphic yeast Yarrowia lipolytica by constructing and characterizing mutant strains with specific gene deletions and integrating exogenous genes to enhance the production of long-chain bases (LCBs) and glucosylceramides (GlcCers). To block the fungal/plant-specific phytosphingosine (PHS) pathway, we deleted the SUR2 gene encoding a sphinganine C4-hydroxylase, resulting in a remarkably elevated secretory production of dihydrosphingosine (DHS) and sphingosine (So) without acetylation.
View Article and Find Full Text PDFJ Lipid Res
December 2024
Department of Medicine, Stony Brook University, Stony Brook, NY; Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY; Northport Veterans Affairs Medical Center, Northport, NY. Electronic address:
Sphingolipids (SPLs) are major components of cell membranes with significant functions. Their production is a highly-regulated multi-step process with the formation of two major intermediates, long chain bases (LCBs) and ceramides. Homologous Orm proteins in both yeast and mammals negatively regulate LCB production by inhibiting serine palmitoyltransferase (SPT), the first enzyme in SPL de novo synthesis.
View Article and Find Full Text PDFHerein, we report the synthesis, characterization, supramolecular gelation and multiple applications of 6-aminocoumarin-derived Schiff bases 1 and 2. Both Schiff bases underwent gelation in DMF-HO (2 : 1, v/v), DMSO-HO (2 : 1, v/v) and dioxane-HO (2 : 1, v/v) involving weak forces. Furthermore, the gels were stable and exhibited good viscoelastic properties.
View Article and Find Full Text PDFPlant Physiol
December 2024
Department of Biochemistry and Molecular Biology, Uniformed Services University of Health Sciences, Bethesda, MD 20814, USA.
Sphingolipid homeostatic regulation is important for balancing plant life and death. Plant cells finely tune sphingolipid biosynthesis to ensure sufficient levels to support growth through their basal functions as major components of endomembranes and the plasma membrane. Conversely, accumulation of sphingolipid biosynthetic intermediates, long-chain bases (LCBs) and ceramides, is associated with programmed cell death.
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