title: Modulation of the expression of membrane-bound CD54 (mCD54) and soluble form of CD54 (sCD54) in endothelial cells by glucosyl transferase inhibitor: possible role of ceramide for the shedding of mCD54.
abstract: 1-Phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) is a synthetic inhibitor toward glucosyl transferase. Here, we showed the functional role of sphingolipids on CD54 expression of endothelial cells (ECs) by the use of PDMP. CD54 mRNA expression in human umbilical vein endothelial cells (HUVECs) was not changed by PDMP; however, PDMP treatment significantly enhanced the expression of membrane-bound CD54 (mCD54) on HUVECs. In contrast, the amount of soluble form of CD54 (sCD54) in the culture supernatants of HUVECs was diminished by PDMP. Similar results were obtained when HUVECs were incubated with metalloproteinase inhibitor, KB-R8301, or in the presence of C2-ceramide. The above effect of PDMP, KB-R8301, and C2-ceramide in HUVECs was commonly found in unstimulated, TNF-alpha-stimulated, and IL-1beta-stimulated HUVECs. These data provide the possibility that the shedding of mCD54 into sCD54 by metalloproteinase-like enzyme is inhibited by PDMP, in which PDMP-induced accumulation of ceramide may act as a second messenger.
authors.affiliation: The First Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, 852-8501, Nagasaki, Japan. atsushik@net.nagasaki-u.ac.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawakami
authors.forename: Ayumi
authors.initials: A
authors.lastname: Hida
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamasaki
authors.forename: Taiichiro
authors.initials: T
authors.lastname: Miyashita
authors.forename: Koto
authors.initials: K
authors.lastname: Nakashima
authors.forename: Fumiko
authors.initials: F
authors.lastname: Tanaka
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ida
authors.forename: Masako
authors.initials: M
authors.lastname: Furuyama
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Migita
authors.forename: Tomoki
authors.initials: T
authors.lastname: Origuchi
authors.forename: Katsumi
authors.initials: K
authors.lastname: Eguchi
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D002518:Ceramides / Q000502:physiology*; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D009025:Morpholines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012995:Solubility
chemical_list: D002518:Ceramides; D017931:DNA Primers; D004791:Enzyme Inhibitors; D009025:Morpholines; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; C033110:RV 538; D005964:Glucosyltransferases