Catfish egg lectin causes rapid activation of multidrug resistance 1 P-glycoprotein as a lipid translocase.
Rhamnose-binding lectin from catfish (Silurus asotus) eggs (SAL) has the ability to induce externalization of phosphatidylserine (PS), followed by cell shrinkage in globotriaosylceramide (Gb3)-expressing Burkitt's lymphoma Raji cells. Because phospholipid scramblase and aminophospholipid translocase did not participate in SAL-induced PS externalization, we examined the relationship of ATP-binding cassette (ABC) transporters, such as multidrug resistance (MDR) 1 P-glycoprotein (MDR1 P-gp) and MDR-associated protein 1 (MRP1), for translocation of PS. Since cyclosporin A (MDR1 P-gp inhibitor) but not MK571 (MRP1 inhibitor) inhibited SAL-induced PS externalization, it was suggested that MDR1 P-gp is involved in this phenomenon. On the other hand, SAL activated both of the ABC transporters for efflux of rhodamine123 (MDR1 P-gp substrate, Rho123) and 5-carboxyfluorescein diacetate (MRP1 substrate, 5-CFDA) in Raji cells. In contrast, SAL did not activate these two transporters in Gb3-negative cell lines, such as K562 and doxorubicin-resistant K562 cells, involving not only PS externalization but also efflux of Rho123 or 5-CFDA. Since Gb3 and both transporters in Raji cells are located in the glycosphingolipid-enriched microdomain (GEM), it is suggested that the binding of SAL to Gb3 localized in the GEM specifically induces MDR1 P-gp activation in Raji cells.
Sugawara
Shigeki
S
Cancer Research Institute, Tohoku Pharmaceutical University, Komatsushima, Sendai, Japan.
Hosono
Masahiro
M
Ogawa
Yukiko
Y
Takayanagi
Motoaki
M
Nitta
Kazuo
K
D000818:Animals; D002397:Catfishes; D045744:Cell Line, Tumor; D029941:Fish Proteins / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology
D029941:Fish Proteins; D037102:Lectins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C402295:rhamnose-binding lectin, catfish; C421109:multidrug resistance-associated protein 1