Long-chain acyl-CoA synthetase 4 modulates prostaglandin E2 release from human arterial smooth muscle cells
Long-chain acyl-CoA synthetases (ACSLs) catalyze the thioesterification of long-chain FAs into their acyl-CoA derivatives. Purified ACSL4 is an arachidonic acid (20:4)-preferring ACSL isoform, and ACSL4 is therefore a probable regulator of lipid mediator production in intact cells. Eicosanoids play...
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| Format: | Article |
| Language: | English |
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Elsevier
2011-04-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520409113 |
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| author | Deidre L. Golej Bardia Askari Farah Kramer Shelley Barnhart Anuradha Vivekanandan-Giri Subramaniam Pennathur Karin E. Bornfeldt |
| author_facet | Deidre L. Golej Bardia Askari Farah Kramer Shelley Barnhart Anuradha Vivekanandan-Giri Subramaniam Pennathur Karin E. Bornfeldt |
| author_sort | Deidre L. Golej |
| collection | DOAJ |
| description | Long-chain acyl-CoA synthetases (ACSLs) catalyze the thioesterification of long-chain FAs into their acyl-CoA derivatives. Purified ACSL4 is an arachidonic acid (20:4)-preferring ACSL isoform, and ACSL4 is therefore a probable regulator of lipid mediator production in intact cells. Eicosanoids play important roles in vascular homeostasis and disease, yet the role of ACSL4 in vascular cells is largely unknown. In the present study, the ACSL4 splice variant expressed in human arterial smooth muscle cells (SMCs) was identified as variant 1. To investigate the function of ACSL4 in SMCs, ACSL4 variant 1 was overexpressed, knocked-down by small interfering RNA, or its enzymatic activity acutely inhibited in these cells. Overexpression of ACSL4 resulted in a markedly increased synthesis of arachidonoyl-CoA, increased 20:4 incorporation into phosphatidylethanolamine, phosphatidylinositol, and triacylglycerol, and reduced cellular levels of unesterified 20:4. Accordingly, secretion of prostaglandin E2 (PGE2) was blunted in ACSL4-overexpressing SMCs compared with controls. Conversely, acute pharmacological inhibition of ACSL4 activity resulted in increased release of PGE2. However, long-term downregulation of ACSL4 resulted in markedly reduced PGE2 secretion. Thus, ACSL4 modulates PGE2 release from human SMCs. ACSL4 may regulate a number of processes dependent on the release of arachidonic acid-derived lipid mediators in the arterial wall. |
| first_indexed | 2024-12-21T18:53:48Z |
| format | Article |
| id | doaj.art-29882182520c4a86a72b758a8fca3cb0 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-21T18:53:48Z |
| publishDate | 2011-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-29882182520c4a86a72b758a8fca3cb02022-12-21T18:53:41ZengElsevierJournal of Lipid Research0022-22752011-04-01524782793Long-chain acyl-CoA synthetase 4 modulates prostaglandin E2 release from human arterial smooth muscle cellsDeidre L. Golej0Bardia Askari1Farah Kramer2Shelley Barnhart3Anuradha Vivekanandan-Giri4Subramaniam Pennathur5Karin E. Bornfeldt6Department of Pathology, Diabetes and Obesity Center of Excellence, University of Washington School of Medicine, Seattle, WA 98109Department of Pathology, Diabetes and Obesity Center of Excellence, University of Washington School of Medicine, Seattle, WA 98109Department of Pathology, Diabetes and Obesity Center of Excellence, University of Washington School of Medicine, Seattle, WA 98109Department of Pathology, Diabetes and Obesity Center of Excellence, University of Washington School of Medicine, Seattle, WA 98109Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109To whom correspondence should be addressed. bornf@u.washington.edu; Department of Pathology, Diabetes and Obesity Center of Excellence, University of Washington School of Medicine, Seattle, WA 98109Long-chain acyl-CoA synthetases (ACSLs) catalyze the thioesterification of long-chain FAs into their acyl-CoA derivatives. Purified ACSL4 is an arachidonic acid (20:4)-preferring ACSL isoform, and ACSL4 is therefore a probable regulator of lipid mediator production in intact cells. Eicosanoids play important roles in vascular homeostasis and disease, yet the role of ACSL4 in vascular cells is largely unknown. In the present study, the ACSL4 splice variant expressed in human arterial smooth muscle cells (SMCs) was identified as variant 1. To investigate the function of ACSL4 in SMCs, ACSL4 variant 1 was overexpressed, knocked-down by small interfering RNA, or its enzymatic activity acutely inhibited in these cells. Overexpression of ACSL4 resulted in a markedly increased synthesis of arachidonoyl-CoA, increased 20:4 incorporation into phosphatidylethanolamine, phosphatidylinositol, and triacylglycerol, and reduced cellular levels of unesterified 20:4. Accordingly, secretion of prostaglandin E2 (PGE2) was blunted in ACSL4-overexpressing SMCs compared with controls. Conversely, acute pharmacological inhibition of ACSL4 activity resulted in increased release of PGE2. However, long-term downregulation of ACSL4 resulted in markedly reduced PGE2 secretion. Thus, ACSL4 modulates PGE2 release from human SMCs. ACSL4 may regulate a number of processes dependent on the release of arachidonic acid-derived lipid mediators in the arterial wall.http://www.sciencedirect.com/science/article/pii/S0022227520409113fatty acidvascular biologyeicosanoid |
| spellingShingle | Deidre L. Golej Bardia Askari Farah Kramer Shelley Barnhart Anuradha Vivekanandan-Giri Subramaniam Pennathur Karin E. Bornfeldt Long-chain acyl-CoA synthetase 4 modulates prostaglandin E2 release from human arterial smooth muscle cells Journal of Lipid Research fatty acid vascular biology eicosanoid |
| title | Long-chain acyl-CoA synthetase 4 modulates prostaglandin E2 release from human arterial smooth muscle cells |
| title_full | Long-chain acyl-CoA synthetase 4 modulates prostaglandin E2 release from human arterial smooth muscle cells |
| title_fullStr | Long-chain acyl-CoA synthetase 4 modulates prostaglandin E2 release from human arterial smooth muscle cells |
| title_full_unstemmed | Long-chain acyl-CoA synthetase 4 modulates prostaglandin E2 release from human arterial smooth muscle cells |
| title_short | Long-chain acyl-CoA synthetase 4 modulates prostaglandin E2 release from human arterial smooth muscle cells |
| title_sort | long chain acyl coa synthetase 4 modulates prostaglandin e2 release from human arterial smooth muscle cells |
| topic | fatty acid vascular biology eicosanoid |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520409113 |
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