Modification of oligosaccharides by reactive oxygen species decreases sialyl lewis x-mediated cell adhesion.
Modification of cell surface oligosaccharides by reactive oxygen species (ROS) and the biological effect of such modifications on cell adhesion were investigated. Treatment of HL60, a human promyelocyte leukemia cell line, with ROS, generated by a combination of hypoxanthine and xanthine oxidase (HX/XO), decreased the sialic acid content on the cell surface, as indicated by a flow cytometric analysis involving sialic acid-specific lectins, and a concomitant increase of free sialic acid was observed in the supernatant. A cell adhesion assay showed that the HX/XO treatment of HL60 cells decreases their capability of binding to human umbilical vein endothelial cells (HUVEC), probably because of an impairment of the interaction involving E-selectin, whereas the decrease in the binding was canceled by the addition of superoxide dismutase (SOD) and catalase. In fact, cell surface sialyl lewis x (sLe x), but not lewis x (Le x), was decreased by HX/XO treatment. Thus, it is more likely that the impaired interaction is based on diminished levels of the selectin ligand. Cleavage of sialic acid by ROS was further verified by the degradation of 4MU-Neu5Ac by HX/XO in the presence of hydrogen peroxide and iron ion. These results indicate that glycosidic linkage of sialic acid is a potential target for superoxide and other related ROS. It is well known that ROS cause cellular damages such as lipid peroxidation and protein oxidation, but, as suggested by the findings reported in the literature, ROS may also regulate cell adhesion via the structural alteration of sialylated oligosaccharides on the cell surface.
Department of Biochemistry, Hyogo College of Medicine, 1-1 Mukogawa, Nishinomiya, Hyogo 663-8501, Japan.
Hironobu
H
Eguchi
Yoshitaka
Y
Ikeda
Tomomi
T
Ookawara
Souichi
S
Koyota
Noriko
N
Fujiwara
Koichi
K
Honke
Peng G
PG
Wang
Naoyuki
N
Taniguchi
Keiichiro
K
Suzuki
D002374:Catalase / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D018922:HL-60 Cells; D006801:Humans; D006923:Hymecromone / Q000031:analogs & derivatives / Q000737:chemistry; D019158:N-Acetylneuraminic Acid / Q000737:chemistry / Q000378:metabolism; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000080506:Sialyl Lewis X Antigen; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014969:Xanthine Oxidase / Q000187:drug effects / Q000378:metabolism
D019040:E-Selectin; D009844:Oligosaccharides; D017382:Reactive Oxygen Species; D000080506:Sialyl Lewis X Antigen; D006923:Hymecromone; C021224:2'-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D019158:N-Acetylneuraminic Acid