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Regulation of very-long acyl chain ceramide synthesis by acyl-CoA-binding protein
| Content Provider | Scilit |
|---|---|
| Author | Ferreira, Natalia Santos Engelsby, Hanne Neess, Ditte Kelly, Samuel L. Volpert, Giora Merrill Jr., Alfred H. Futerman Jr., Anthony H. Faergeman, Nils J. |
| Copyright Year | 2017 |
| Description | Journal: Journal of Biological Chemistry Ceramide and more complex sphingolipids constitute a diverse group of lipids, which serve important roles as structural entities of biological membranes and as regulators of cellular growth, differentiation, and development. Thus, ceramides are vital players in numerous diseases including metabolic and cardiovascular diseases as well as neurological disorders. Here we show that acyl coenzyme A binding protein (ACBP) potently facilitates very-long acyl chain ceramide synthesis. ACBP increases the activity of ceramide synthase 2 (CerS2) by more than 2-fold and CerS3 activity by 7-fold. ACBP binds very long-chain acyl-CoA esters, which is required for its ability to stimulate CerS activity. We also show that high-speed liver cytosol from wild type mice activates CerS3 activity, while cytosol from ACBP knock out mice does not. Consistently, CerS2 and CerS3 activities are significantly reduced in the testes of ACBP-/- mice, concomitant with a significant reduction in long- and very-long chain ceramide levels. Importantly, we show that ACBP interacts with CerS2 and CerS3. Our data uncover a novel mode of regulation of very-long acyl chain ceramide synthesis by ACBP, which we anticipate is of crucial importance in understanding the regulation of ceramide metabolism in pathogenesis. |
| Related Links | http://www.jbc.org/content/292/18/7588.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5418056/pdf http://www.jbc.org/content/early/2017/03/19/jbc.M117.785345.full.pdf |
| Ending Page | 7597 |
| Page Count | 10 |
| Starting Page | 7588 |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| DOI | 10.1074/jbc.m117.785345 |
| Journal | Journal of Biological Chemistry |
| Issue Number | 18 |
| Volume Number | 292 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2017-03-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Biological Chemistry Biochemistry and Molecular Biology Ceramide Synthase Fatty Acid Metabolism Lipid Binding Protein |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |