Dihydroceramides: From Bit Players to Lead Actors

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 g...

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Bibliographic Details
Published in:The Journal of biological chemistry 2015-06, Vol.290 (25), p.15371-15379
Main Authors: Siddique, Monowarul Mobin, Li, Ying, Chaurasia, Bhagirath, Kaddai, Vincent A., Summers, Scott A.
Format: Article
Language:English
Subjects:
Animals
apoptosis
Autophagy
Cell Proliferation
cell signaling
ceramides
Ceramides - genetics
Ceramides - metabolism
Diabetes Mellitus - diagnosis
Diabetes Mellitus - genetics
Diabetes Mellitus - metabolism
Diabetes Mellitus - pathology
dihydroceramide
Humans
hypoxia
membrane
Minireviews
Neoplasms - diagnosis
Neoplasms - genetics
Neoplasms - metabolism
Neoplasms - pathology
Neurodegenerative Diseases - diagnosis
Neurodegenerative Diseases - genetics
Neurodegenerative Diseases - metabolism
Neurodegenerative Diseases - pathology
proliferation
Reperfusion Injury - diagnosis
Reperfusion Injury - genetics
Reperfusion Injury - metabolism
Reperfusion Injury - pathology
sphingolipids
Sphingomyelins - genetics
Sphingomyelins - metabolism
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.R115.653204