Dihydroceramides: From Bit Players to Lead Actors

被引:113
作者
Siddique, Monowarul Mobin [1 ]
Li, Ying [1 ]
Chaurasia, Bhagirath [1 ]
Kaddai, Vincent A. [1 ]
Summers, Scott A. [1 ]
机构
[1] Baker IDI Heart & Diabet Inst, Melbourne, Vic 3004, Australia
关键词
apoptosis; autophagy; cell signaling; hypoxia; membrane; ceramides; sphingolipids; dihydroceramide; proliferation; NOVO SPHINGOLIPID BIOSYNTHESIS; INDUCED INSULIN-RESISTANCE; DIET-INDUCED OBESITY; CELL-DEATH; CERAMIDE SYNTHESIS; MEMBRANE-STRUCTURE; DESATURASE; AKT KINASE; APOPTOSIS; INDUCTION;
D O I
10.1074/jbc.R115.653204
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Sphingolipid synthesis involves a highly conserved biosynthetic pathway that produces fundamental precursors of complex sphingolipids. The final reaction involves the insertion of a double bond into dihydroceramides to generate the more abundant ceramides, which are converted to sphingomyelins and glucosylceramides/gangliosides by the addition of polar head groups. Although ceramides have long been known to mediate cellular stress responses, the dihydroceramides that are transiently produced during de novo sphingolipid synthesis were deemed inert. Evidence published in the last few years suggests that these dihydroceramides accumulate to a far greater extent in tissues than previously thought. Moreover, they have biological functions that are distinct and non-overlapping with those of the more prevalent ceramides. Roles are being uncovered in autophagy, hypoxia, and cellular proliferation, and the lipids are now implicated in the etiology, treatment, and/or diagnosis of diabetes, cancer, ischemia/reperfusion injury, and neurodegenerative diseases. This minireview summarizes recent findings on this emerging class of bioactive lipids.
引用
收藏
页码:15371 / 15379
页数:9
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