Regulation of very-long acyl chain ceramide synthesis by acyl-CoA-binding protein
| Autor: | Giora Volpert, Natalia Santos Ferreira, Samuel Kelly, Nils J. Færgeman, Hanne Engelsby, Ditte Neess, Alfred H. Merrill, Anthony H. Futerman |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Ceramide Biology Ceramides Biochemistry Cell Line 03 medical and health sciences chemistry.chemical_compound Mice Acyl-CoA-binding protein Sphingosine N-Acyltransferase Sphingosine N-acyltransferase Journal Article Animals Humans Molecular Biology Ceramide synthase Diazepam Binding Inhibitor Mice Knockout 030102 biochemistry & molecular biology Tumor Suppressor Proteins Fatty Acids Ceramide synthase 2 Membrane Proteins Cell Biology Lipid signaling Lipids Sphingolipid Cytosol 030104 developmental biology chemistry |
| Zdroj: | Ferreira, N S, Engelsby, H, Neess, D, Kelly, S L, Volpert, G, Merrill, A H, Futerman, A H & Færgeman, N J 2017, ' Regulation of very-long acyl chain ceramide synthesis by acyl-CoA-binding protein ', Journal of Biological Chemistry, vol. 292, no. 18, pp. 7588-7597 . https://doi.org/10.1074/jbc.M117.785345 |
| DOI: | 10.1074/jbc.M117.785345 |
| Popis: | Ceramide and more complex sphingolipids constitute a diverse group of lipids that 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, whereas 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. |
| Databáze: | OpenAIRE |
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