| Ceramide synthase 4 and de novo production of ceramides with specific N-acyl chain lengths are involved in gluco-lipotoxicity-induced apoptosis of INS-1 β-cells. | |
| | |
MedLine Citation:
|
PMID: 21592087 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Pancreatic β-cell apoptosis induced by palmitate requires high glucose concentrations. Ceramides have been suggested to be important mediators of gluco-lipotoxicity-induced β-cell apoptosis. In INS-1 β-cells, 0.4 mM palmitate with 5 mM glucose increased the levels of dihydrosphingosine and dihydroceramides, two lipid intermediates in the de novo biosynthesis of ceramides, without inducing apoptosis. Increasing glucose concentrations to 30 mM amplified palmitate-induced accumulation of dihydrosphingosine and the formation of (dihydro)-ceramides. Of note, gluco-lipotoxicity specifically induced the formation of 18:0, 22:0 and 24:1 (dihydro)-ceramide molecular species, which was associated with the up-regulation of ceramide synthase 4 (CerS4) levels. Fumonisin-B1, a ceramide synthase inhibitor, partially blocked apoptosis induced by gluco-lipotoxicity. In contrast, apoptosis was potentiated in the presence of D,L-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol, an inhibitor of glucosyl-ceramide synthase. Moreover, over-expression of CerS4 amplified ceramide production and apoptosis induced by palmitate with 30 mM glucose whereas down-regulation of CerS4 by siRNA reduced apoptosis. CerS4 also potentiates ceramide accumulation and apoptosis induced by another saturated fatty acid, stearate. Collectively, our results suggest that gluco-lipotoxicity induced β-cell apoptosis through a dual mechanism involving the de novo ceramide biosynthesis and the formation of ceramides with specific N-acyl chain lengths rather than an overall increase of ceramide content. |
| | |
Authors:
|
Julien Véret; Nicolas Coant; Evgeny Berdyshev; Anastasia Skobeleva; Nicole Therville; Danielle Bailbé; Irina Gorshkova; Viswanathan Natarajan; Bernard Portha; Herve Le Stunff |
Related Documents
:
|
10752747 - Altered interleukin-6 expression in fibroblasts from hypertrophic burn scars. 17020997 - Mln120b, a novel ikappab kinase beta inhibitor, blocks multiple myeloma cell growth in ... 20445007 - Delayed addition of glucocorticoids selectively suppresses cytokine production in stimu... 16860877 - Cytokines in reproductive remodeling of molting white leghorn hens. 21731667 - An observational cohort study of the kynurenine to tryptophan ratio in sepsis: associat... 2521877 - Development of surface membrane characteristics of "premedullary" macrophages in organ ... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-5-19 |
Journal Detail:
|
Title: The Biochemical journal Volume: - ISSN: 1470-8728 ISO Abbreviation: - Publication Date: 2011 May |
Date Detail:
|
Created Date: 2011-5-19 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 2984726R Medline TA: Biochem J Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Patentable Subject Matter: Morally Neutral and Context Free.
Next Document: Intrinsic membrane association of the cytoplasmic tail of influenza virus M2 protein and lateral mem...