Sphingosine mediates FTY720-induced apoptosis in LLC-PK1 cells.
- Author:
Woo Jin LEE
1
;
Hwan Soo YOO
;
Pann Ghill SUH
;
Jong Seok LIM
;
Seikwan OH
;
Yong Moon LEE
Author Information
1. College of Pharmacy, Chungbuk National University, Chongju 361-763, Korea. ymleefn@chungbuk.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
apoptosis;
FTY720;
LLC-PK1 cells;
sphingosine;
sphingosine kinase
- MeSH:
Animals;
Apoptosis/*physiology;
Caspases/biosynthesis;
Cell Line;
DNA Fragmentation;
Endothelial Cells/drug effects;
Enzyme Inhibitors/*pharmacology;
Kidney/cytology;
Phosphotransferases (Alcohol Group Acceptor)/*antagonists & inhibitors/physiology;
Propylene Glycols/*pharmacology;
Research Support, Non-U.S. Gov't;
Sphingosine/pharmacology/*physiology;
Swine;
Up-Regulation
- From:Experimental & Molecular Medicine
2004;36(5):420-427
- CountryRepublic of Korea
- Language:English
-
Abstract:
FTY720, a synthetic sphingoid base analog, was examined as a new sphingosine kinase inhibitor, which converts endogenous sphingosine into its phosphate form. With 20 micrometer of FTY720, sphingosine accumulated in the LLC-PK1 cells in a time- and dose-dependent manner. The FTY720 treated cells showed a high concentration of fragmented DNA, a high caspase-3 like activity and TUNEL staining cells. It was also found that the sphingosine and sphinganine level increased in a time- and dose-dependent manner within 12 h after the FTY720 treatment. The sphingosine kinase activity was reduced by FTY720 as much as other sphingosine kinase inhibitors, N, N-dimethylsphingosine (DMS), dl-threo-dihydrosphingosine (DHS). The fragmented DNA content as a result of the 20 micrometer of FTY720 treatment and by 5 micrometer of the exogenously added BSA-sphingosine complex indicated typical apoptosis. Under similar conditions, the accumulated sphingosine concentration in all the cells was almost identical even though the sphingosine distribution inside the cells was somewhat different. These results indicate that the FTY720 induced apoptosis is associated with the inhibition of the sphingosine kinase activity and is strongly associated with the successive accumulation of sphingosine.
