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.
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.
Kawakami
Atsushi
A
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
Hida
Ayumi
A
Yamasaki
Satoshi
S
Miyashita
Taiichiro
T
Nakashima
Koto
K
Tanaka
Fumiko
F
Ida
Hiroaki
H
Furuyama
Masako
M
Migita
Kiyoshi
K
Origuchi
Tomoki
T
Eguchi
Katsumi
K
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
D002518:Ceramides; D017931:DNA Primers; D004791:Enzyme Inhibitors; D009025:Morpholines; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; C033110:RV 538; D005964:Glucosyltransferases