TY - JOUR
T1 - Parasporin-2 requires GPI-anchored proteins for the efficient cytocidal action to human hepatoma cells
AU - Kitada, Sakae
AU - Abe, Yuichi
AU - Maeda, Toshitaka
AU - Shimada, Hiroyasu
N1 - Funding Information:
We thank Dr. Hanada for kindly gift of a mutant CHO-K1 cell line, LY-B, and Dr. Kuge and Ogishima for useful discussions. This work was supported in part by Grants-in-Aid for Scientific Research (to S.K./ 18687007 ) from the Ministry of Education, Science, Sports and Culture of the Japanese Government , Grants-in-Aid for Research (to S.K./ 08A02203a ) from the New Energy and Industrial Technology Development Organization (NEDO), and the Takeda Science Foundation (to S.K.).
PY - 2009/10/1
Y1 - 2009/10/1
N2 - Parasporin-2 (PS2) is a Bacillus thuringiensis inclusion protein that reacts intensively with human hepatoma cells. This antitumour toxin oligomerizes at the cell surface via binding to lipid rafts, leading to the cell lysis with typical blebs around peripheral cells. We find here that glycosylphosphatidylinositol (GPI)-anchored proteins are involved in the cytocidal actions. Depletion of the cellular cholesterol and loss of sphingolipid in lipid rafts slightly decreased cytolysis by PS2. Beyond those, the cells temporally resisted PS2 with reduction of the toxin binding after GPI-anchored proteins were cleaved off by phosphatidylinositol-specific phospholipase C. PS2 and aerolysin showed individual cytocidal specificity while aerolysin's receptor is GPI-anchored proteins. When we confirmed expression of GPI-anchored proteins on four cell lines, showing different cytotoxicity by PS2, GPI-anchored proteins were evenly expressed on the cells. Therefore, PS2 requires a kind of GPI-anchored proteins for the effective cytolysis.
AB - Parasporin-2 (PS2) is a Bacillus thuringiensis inclusion protein that reacts intensively with human hepatoma cells. This antitumour toxin oligomerizes at the cell surface via binding to lipid rafts, leading to the cell lysis with typical blebs around peripheral cells. We find here that glycosylphosphatidylinositol (GPI)-anchored proteins are involved in the cytocidal actions. Depletion of the cellular cholesterol and loss of sphingolipid in lipid rafts slightly decreased cytolysis by PS2. Beyond those, the cells temporally resisted PS2 with reduction of the toxin binding after GPI-anchored proteins were cleaved off by phosphatidylinositol-specific phospholipase C. PS2 and aerolysin showed individual cytocidal specificity while aerolysin's receptor is GPI-anchored proteins. When we confirmed expression of GPI-anchored proteins on four cell lines, showing different cytotoxicity by PS2, GPI-anchored proteins were evenly expressed on the cells. Therefore, PS2 requires a kind of GPI-anchored proteins for the effective cytolysis.
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U2 - 10.1016/j.tox.2009.07.016
DO - 10.1016/j.tox.2009.07.016
M3 - Article
C2 - 19646502
AN - SCOPUS:69449101087
SN - 0300-483X
VL - 264
SP - 80
EP - 88
JO - Toxicology
JF - Toxicology
IS - 1-2
ER -