GinsenosideRhinducesligand-independentFasactivationvialipidraftdisruption.docVIP

Biochemical and Biophysical Research Communications 385 (2009) 154–159 Contents lists available at HYPERLINK /science/journal/0006291XScienceDirect Biochemical and Biophysical Research Communications j o u r n a l h o m e p a g e : HYPERLINK /locate/ybbrcw w w . e l s e v i e r . c o m / l o c a t e / y b b r c Ginsenoside Rh2 induces ligand-independent Fas activation via lipid raft disruption Jae-Sung Yia, Hyo-Jung Chooa, Bong-Rae Chob, Hwan-Myung Kimc, Yong-Nyun Kimd, Young-Mi Hama,*, Young-Gyu Koa,* aCollege of Life Sciences and Biotechnology, Korea University, 1, 5-ka, Anam-dong, Sungbuk-gu, Seoul 136-701, Republic of Korea b Department of Chemistry, Korea University, Seoul 136-701, Republic of Korea c Department of Chemistry, Ajou University, Suwon, Kyunggi-Do 443-749, Republic of Korea d Division of Speci?c Organs Center, National Cancer Center, Kyunggi-Do 411-769, Republic of Korea  a r t i c l e i n f o Article history: Received 7 May 2009 Available online 13 May 2009 Keywords: Lipid rafts Ginsenoside Rh2 Fas activation Apoptosis Introduction  a b s t r a c t Lipid rafts are plasma membrane platforms mediating signal transduction pathways for cellular prolifer- ation, differentiation and apoptosis. Here, we show that membrane ?uidity was increased in HeLa cells following treatment with ginsenoside Rh2 (Rh2), as determined by cell staining with carboxy-laurdan (C-laurdan), a two-photon dye designed for measuring membrane hydrophobicity. In the presence of Rh2, caveolin-1 appeared in non-raft fractions after sucrose gradient ultracentrifugation. In addition, caveolin-1 and GM1, lipid raft landmarkers, were internalized within cells after exposure to Rh2, indicat- ing that Rh2 might disrupt lipid rafts. Since cholesterol overloading, which forti?es lipid rafts, prevented an increase in Rh2-induced membrane ?uidity, caveolin-1 internalization and apoptosis, lipid rafts appear to be essential for Rh2-induced apoptosis. Moreover, Rh2-induced Fas oligomeri