[Regulation of globotriaosylceramide (Gb3)-mediated signal transduction by rhamnose-binding lectin].
Silurus asotus (catfish) egg lectin (SAL) has potent affinity to Gal alpha-linked carbohydrate chains of not only glycoproteins but also glycosphingolipids such as globotriaosylceramide (Gb3). SAL selectively bound to Gb3 localized in glycosphingolipid-enriched microdomain (GEM) of Gb3-expressing (Gb3(+)) Burkitt's lymphoma cells. Since treatment of Gb3(+) cells with SAL caused an increase in externalization of phosphatidylserine via activation of P-glycoprotein, and apoptotic volume decrease via activation of G-protein activated K(+) channel-1, SAL may function as an inducer of early apoptotic signal; however, neither caspase-8 and -3 activation nor DNA fragmentation was observed. We therefore investigated whether cell proliferation and viability were altered in SAL-treated Raji cells. SAL caused reduction of Raji cell proliferation without cytotoxicity. Although SAL did not induce apoptotic cell death to Gb3-expressing cells, it functionally behaved as a regulator of cell proliferation. SAL activated the suppression system of cell proliferation, such as down-regulation of c-myc and cdk4, and up-regulation of p21 and p27, inducing G1 arrest of the cell cycle, and consequently inhibited cell proliferation of Raji cells. Therefore, we conclude that SAL leads the cells to early apoptotic status but not late apoptotic (necrotic) status via binding to Gb3 existing in GEM, and that this binding is a prerequisite condition to induce cell cycle stop signal.
Nitta
Kazuo
K
Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai, Japan. knitta@tohoku-pharm.ac.jp
Kawano
Tasuku
T
Sugawara
Shigeki
S
Hosono
Masahiro
M
D000818:Animals; D002051:Burkitt Lymphoma / Q000628:therapy; D049109:Cell Proliferation / Q000187:drug effects; D003864:Depression, Chemical; D029941:Fish Proteins / Q000235:genetics / Q000502:physiology / Q000627:therapeutic use; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D006801:Humans; D037102:Lectins / Q000235:genetics / Q000502:physiology / Q000627:therapeutic use; D010718:Phosphatidylserines / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology*; D014281:Trihexosylceramides / Q000502:physiology*
D029941:Fish Proteins; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D037102:Lectins; D010718:Phosphatidylserines; D014281:Trihexosylceramides; C402295:rhamnose-binding lectin, catfish; C018549:globotriaosylceramide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011188:Potassium