RRC ID 38248
Author Fukunaga M, Nunomura S, Nishida S, Endo K, Gon Y, Hashimoto S, Hashimoto Y, Okayama Y, Makishima M, Ra C.
Title Mast cell death induced by 24(S),25-epoxycholesterol.
Journal Exp Cell Res
Abstract Mast cell is one of the central effectors in inflammatory responses. Recent studies suggest that a promising therapeutic approach for various inflammatory immune diseases, including rheumatoid arthritis, multiple sclerosis, and type I allergies, is to inhibit mast cell growth and/or survival. Studies also indicate that a balanced lipid metabolism is crucial for regulating the life span of cells. Oxysterol is a well-known regulator of lipid metabolism and has diverse functions, such as inhibition of the mevalonate isoprenoid pathway, efflux of free cholesterols, and synthesis of cholesterol esters. Here, we show that 24(S),25-epoxycholesterol, a representative endogenous oxysterol, induces apoptosis in bone marrow-derived murine mast cells. Furthermore, we have revealed, for the first time, that the accumulation of neutral lipids catalyzed by acyl-CoA:cholesterol acyltransferase in the cells was involved in induction of mast cell apoptosis. Our present findings confer new insights into the roles of lipid metabolism during oxysterol-mediated mast cell apoptosis.
Volume 316(19)
Pages 3272-81
Published 2010-11-15
DOI 10.1016/j.yexcr.2010.09.002
PII S0014-4827(10)00427-1
PMID 20854813
MeSH Amides / pharmacology Animals Caspase 3 / metabolism Caspase 7 / metabolism Caspase Inhibitors Cell Death / drug effects Cells, Cultured Cholesterol / analogs & derivatives* Cholesterol / pharmacology Cytoprotection / drug effects DNA Fragmentation / drug effects Enzyme Activation / drug effects Lipid Metabolism / drug effects Liver X Receptors Mast Cells / cytology* Mast Cells / drug effects* Mast Cells / enzymology Mevalonic Acid / pharmacology Mice Mice, Inbred C57BL Organosilicon Compounds / pharmacology Orphan Nuclear Receptors / antagonists & inhibitors Orphan Nuclear Receptors / metabolism Protease Inhibitors / pharmacology Sterol O-Acyltransferase / antagonists & inhibitors Sterol O-Acyltransferase / metabolism
IF 3.383
Times Cited 10
Cord blood stem cells for research