| Cardiomyocyte specific deficiency of serine palmitoyltransferase subunit 2 reduces ceramide but leads to cardiac dysfunction. | |
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MedLine Citation:
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PMID: 22493506 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The role of serine palmitoyltransferase (SPT) and de novo ceramide biosynthesis in cardiac ceramide and sphingomyelin metabolism is unclear. To determine whether the de novo synthetic pathways, rather than ceramide uptake from circulating lipoproteins, is important for heart ceramide levels, we created cardiomyocyte-specific deficiency of Sptlc2, a subunit of SPT. Heart-specific Sptlc2-deficient (hSptlc2 KO) mice had a >35% reduction in ceramide, which was limited to C18:0 and very long chain ceramides. Sphingomyelinase expression, and levels of sphingomyelin and diacylglycerol were unchanged. But surprisingly phospholipids and acyl CoAs contained increased saturated long chain fatty acids. hSptlc2 KO mice had decreased fractional shortening and thinning of the cardiac wall. While the genes regulating glucose and fatty acid metabolism were not changed, expression of cardiac failure markers and the genes involved in the formation of extracellular matrices were up-regulated in hSptlc2 KO hearts. In addition, ER-stress markers were up-regulated leading to increased apoptosis. These results suggest that Sptlc2-mediated de novo ceramide synthesis is an essential source of C18:0 and very long chain, but not of shorter chain, ceramides in the heart. Changes in heart lipids other than ceramide levels lead to cardiac toxicity. |
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Authors:
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Su-Yeon Lee; Jung Ran Kim; Yunying Hu; Raffay Khan; Su-Jung Kim; Kalyani G Bharadwaj; Mercy M Davidson; Cheol-Soo Choi; Kyong-Oh Shin; Yong-Moon Lee; Woo-Jin Park; In-Sun Park; Xian-Cheng Jiang; Ira J Goldberg; Tae-Sik Park |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-04-09 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 287 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-05-28 Completed Date: 2012-08-15 Revised Date: 2013-05-28 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 18429-39 Citation Subset: IM |
Affiliation:
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Department of Life Science, Gachon University, Seongnam-Si, Gyeonggi-Do, Republic of Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Glucose / metabolism Blotting, Western Cells, Cultured Ceramides / metabolism* Heart / physiopathology* In Situ Nick-End Labeling Lipids / blood Mice Mice, Inbred C57BL Mice, Knockout Myocardium / enzymology* Serine C-Palmitoyltransferase / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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HL45095/HL/NHLBI NIH HHS; HL73029/HL/NHLBI NIH HHS; R01 HL045095/HL/NHLBI NIH HHS; R01 HL073029/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/Ceramides; 0/Lipids; EC 2.3.1.50/Serine C-Palmitoyltransferase |
| Comments/Corrections | |
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