Mast cell death induced by 24(S),25-epoxycholesterol.
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.
Fukunaga
Makiko
M
Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Science, 30-1 Oyaguchikami-cho Itabashi-ku, Tokyo 173-8610, Japan.
Nunomura
Satoshi
S
Nishida
Shigeru
S
Endo
Kaori
K
Gon
Yasuhiro
Y
Hashimoto
Shu
S
Hashimoto
Yuichi
Y
Okayama
Yoshimichi
Y
Makishima
Makoto
M
Ra
Chisei
C
D000577:Amides / Q000494:pharmacology; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D061945:Caspase Inhibitors; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D019610:Cytoprotection / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects; D000071518:Liver X Receptors; D008407:Mast Cells / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D008798:Mevalonic Acid / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D017646:Organosilicon Compounds / Q000494:pharmacology; D057093:Orphan Nuclear Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism
D000577:Amides; D061945:Caspase Inhibitors; D000071518:Liver X Receptors; D017646:Organosilicon Compounds; D057093:Orphan Nuclear Receptors; D011480:Protease Inhibitors; C028358:24,25-epoxycholesterol; C040256:SAN 58035; D002784:Cholesterol; D002785:Sterol O-Acyltransferase; D053148:Caspase 3; D053179:Caspase 7; D008798:Mevalonic Acid