Acetyl-CoA carboxylase 1 regulates endothelial cell migration by shifting the phospholipid composition
| Autor: | Oliver Werz, Iris Bischoff, Rolf Müller, Helmut Pein, Nelli Keksel, Anna Stark, Andreas Koeberle, Daniel K. Glatzel, Konstantin Löser, Robert Fürst |
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| Přispěvatelé: | HIPS, Helmholtz-Institute für pharmazeutische Forschung Saarland, Universitätscampus E8.1, 66123 Saarbrücken, Germany. |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cell Survival Phospholipid soraphen QD415-436 behavioral disciplines and activities Biochemistry 03 medical and health sciences chemistry.chemical_compound vascular biology/endothelial cells 0302 clinical medicine Endocrinology Cell Movement Membrane fluidity Gene silencing Humans Research Articles Cells Cultured Phospholipids Fatty acid metabolism Endothelial Cells membranes/fluidity Cell migration Cell Biology Acetyl-CoA Carboxylase 1 Pyruvate carboxylase Cell biology Endothelial stem cell stomatognathic diseases 030104 developmental biology chemistry nervous system phospholipids/phosphatidylglycerol 030220 oncology & carcinogenesis lipidomics Macrolides fatty acid/biosynthesis Acetyl-CoA Carboxylase |
| Zdroj: | Journal of Lipid Research, Vol 59, Iss 2, Pp 298-311 (2018) |
| ISSN: | 0022-2275 |
| Popis: | The enzyme acetyl-CoA carboxylase (ACC) plays a crucial role in fatty acid metabolism. In recent years, ACC has been recognized as a promising drug target for treating different diseases. However, the role of ACC in vascular endothelial cells (ECs) has been neglected so far. To characterize the role of ACC, we used the ACC inhibitor, soraphen A, as a chemical tool, and also a gene silencing approach. We found that ACC1 was the predominant isoform in human umbilical vein ECs as well as in human microvascular ECs and that soraphen A reduced the levels of malonyl-CoA. We revealed that ACC inhibition shifted the lipid composition of EC membranes. Accordingly, membrane fluidity, filopodia formation, and migratory capacity were reduced. The antimigratory action of soraphen A depended on an increase in the cellular proportion of PUFAs and, most importantly, on a decreased level of phosphatidylglycerol. Our study provides a causal link between ACC, membrane lipid composition, and cell migration in ECs. Soraphen A represents a useful chemical tool to investigate the role of fatty acid metabolism in ECs and ACC inhibition offers a new and valuable therapeutic perspective for the treatment of EC migration-related diseases. |
| Databáze: | OpenAIRE |
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