Structures and biological activity of phosphorylated dihydroceramides of Porphyromonas gingivalis

Frank C. Nichols; Birgit Riep; JiYoung Mun; Martha D. Morton; Mike T. Bojarski; Floyd E. Dewhirst; Michael B. Smith

Journal of Lipid Research (Dec 2004)

Structures and biological activity of phosphorylated dihydroceramides of Porphyromonas gingivalis

Frank C. Nichols,
Birgit Riep,
JiYoung Mun,
Martha D. Morton,
Mike T. Bojarski,
Floyd E. Dewhirst,
Michael B. Smith

Affiliations

Frank C. Nichols: Department of Periodontology, University of Connecticut School of Dental Medicine, 263 Farmington Avenue, Farmington, CT; Department of Periodontology and Synoptic Dentistry, Charité University of Medicine Berlin, Augustenburger Platz 1, Berlin, Germany; Department of Chemistry, U3060 University of Connecticut, 55 North Eagleville Road, Storrs, CT; Department of Molecular Genetics, Forsyth Institute, 140 The Fenway, Boston, MA
Birgit Riep: Department of Periodontology, University of Connecticut School of Dental Medicine, 263 Farmington Avenue, Farmington, CT; Department of Periodontology and Synoptic Dentistry, Charité University of Medicine Berlin, Augustenburger Platz 1, Berlin, Germany; Department of Chemistry, U3060 University of Connecticut, 55 North Eagleville Road, Storrs, CT; Department of Molecular Genetics, Forsyth Institute, 140 The Fenway, Boston, MA
JiYoung Mun: Department of Periodontology, University of Connecticut School of Dental Medicine, 263 Farmington Avenue, Farmington, CT; Department of Periodontology and Synoptic Dentistry, Charité University of Medicine Berlin, Augustenburger Platz 1, Berlin, Germany; Department of Chemistry, U3060 University of Connecticut, 55 North Eagleville Road, Storrs, CT; Department of Molecular Genetics, Forsyth Institute, 140 The Fenway, Boston, MA
Martha D. Morton: Department of Periodontology, University of Connecticut School of Dental Medicine, 263 Farmington Avenue, Farmington, CT; Department of Periodontology and Synoptic Dentistry, Charité University of Medicine Berlin, Augustenburger Platz 1, Berlin, Germany; Department of Chemistry, U3060 University of Connecticut, 55 North Eagleville Road, Storrs, CT; Department of Molecular Genetics, Forsyth Institute, 140 The Fenway, Boston, MA
Mike T. Bojarski: Department of Periodontology, University of Connecticut School of Dental Medicine, 263 Farmington Avenue, Farmington, CT; Department of Periodontology and Synoptic Dentistry, Charité University of Medicine Berlin, Augustenburger Platz 1, Berlin, Germany; Department of Chemistry, U3060 University of Connecticut, 55 North Eagleville Road, Storrs, CT; Department of Molecular Genetics, Forsyth Institute, 140 The Fenway, Boston, MA
Floyd E. Dewhirst: Department of Periodontology, University of Connecticut School of Dental Medicine, 263 Farmington Avenue, Farmington, CT; Department of Periodontology and Synoptic Dentistry, Charité University of Medicine Berlin, Augustenburger Platz 1, Berlin, Germany; Department of Chemistry, U3060 University of Connecticut, 55 North Eagleville Road, Storrs, CT; Department of Molecular Genetics, Forsyth Institute, 140 The Fenway, Boston, MA
Michael B. Smith: Department of Periodontology, University of Connecticut School of Dental Medicine, 263 Farmington Avenue, Farmington, CT; Department of Periodontology and Synoptic Dentistry, Charité University of Medicine Berlin, Augustenburger Platz 1, Berlin, Germany; Department of Chemistry, U3060 University of Connecticut, 55 North Eagleville Road, Storrs, CT; Department of Molecular Genetics, Forsyth Institute, 140 The Fenway, Boston, MA

Journal volume & issue: Vol. 45, no. 12
pp. 2317 – 2330

Abstract

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Porphyromonas gingivalis, a recognized periodontal pathogen, synthesizes free ceramides as well as other phosphorylated ceramide lipids. The purpose of this study was to separate complex lipids of P. gingivalis by high-performance liquid chromatography (HPLC) and determine the structures and biological activities of the major ceramide classes. Using gas chromatography-mass spectrometry, electrospray tandem mass spectrometry (ESI-MS/MS) and NMR analyses, three major classes of dihydroceramides were identified in specific HPLC fractions, with all classes containing the same dihydroceramide base structures (3-OH isoC17:0 in amide linkage to saturated long-chain bases of 17, 18, or 19 carbons). The free dihydroceramide class recovered in HPLC fractions 7–8 revealed little biological activity. HPLC fraction 20 dihydroceramides, substituted with 1-O-phosphoglycerol and isoC15:0 linked to the hydroxyl of 3-OH isoC17:0, significantly potentiated interleukin-1β (IL-1β)-mediated prostaglandin secretion and produced marked alterations in fibroblast morphology. HPLC fraction 28 dihydroceramides, substituted with 1-O-phosphoethanolamine, demonstrated little capacity to potentiate IL-1β-mediated prostaglandin secretion.The novel phosphorylated dihydroceramides synthesized by P. gingivalis demonstrate varying biological activities based on the phosphorylated head group substitution and/or the addition of esterified fatty acid. These results also demonstrate the strong virulence capacity of phosphoglycerol dihydroceramides of P. gingivalis to promote inflammatory factor secretion from IL-1β-treated fibroblasts and to produce marked alterations in cell morphology in culture.

Published in Journal of Lipid Research

ISSN: 0022-2275 (Print); 1539-7262 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry
Website: https://www.journals.elsevier.com/journal-of-lipid-research

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