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A shift in sphingolipid composition from C24 to C16 increases susceptibility to apoptosis in HeLa cells

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Title: A shift in sphingolipid composition from C24 to C16 increases susceptibility to apoptosis in HeLa cells
Authors: Sassa, Takayuki Browse this author →KAKEN DB
Suto, Shota Browse this author
Okayasu, Yuriko Browse this author
Kihara, Akio Browse this author →KAKEN DB
Keywords: Ceramide
Sphingolipid
Very long-chain fatty acid
Apoptosis
Cisplatin
Caspase
Issue Date: Jul-2012
Publisher: Elsevier B.V.
Journal Title: Biochimica et Biophysica Acta (BBA): Molecular and Cell Biology of Lipids
Volume: 1821
Issue: 7
Start Page: 1031
End Page: 1037
Publisher DOI: 10.1016/j.bbalip.2012.04.008
PMID: 22579584
Abstract: Sphingolipids, major lipid components of the eukaryotic plasma membrane, have a variety of physiological functions and have been associated with many diseases. They have also been implicated in apoptosis. Sphingolipids are heterogeneous in their acyl chain length, with long-chain (C16) and very long-chain (C24) sphingolipids being predominant in most mammalian tissues. We demonstrate that knockdown of ELOVL1 or CERS2, which catalyze synthesis of C24 acyl-CoAs and C24 ceramide, respectively, drastically reduced C24 sphingolipid levels with a complementary increase in C16 sphingolipids. Under ELOVL1 or CERS2 knockdown conditions, cisplatin-induced apoptosis significantly increased. Enhanced sensitivity to cisplatin-induced apoptosis exhibited close correlation with increases in caspase-3/7 activity. No significant alterations in sphingolipid metabolism such as ceramide generation were apparent with the cisplatin-induced apoptosis, and inhibitors of ceramide generation had no effect on the apoptosis. Apoptosis induced by UV radiation or C6 ceramides also increased in ELOVL1 or CERS2 knockdown cells. Changes in the composition of sphingolipid chain length may affect susceptibility to stimuli-induced apoptosis by affecting the properties of cell membranes, such as lipid microdomain/raft formation.
Type: article (author version)
URI: http://hdl.handle.net/2115/49558
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 木原 章雄

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