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Triacsin C is a time dependent inhibitor of Long Chain Fatty Acyl CoA Synthetase (Acsl) in endothelial cells
Author(s) -
Pillai Venkateswaran C,
Chen Yi Qing,
Crumley Jason,
Bazinet Richard P,
Rapoport Stanley I,
Weis Margaret T
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.792.12
Subject(s) - palmitic acid , in vitro , chemistry , negative control , fatty acid , biology , biochemistry , medicine , traditional medicine
The literature indicates that triacsin C is a competitive inhibitor of Acsl. We found that, in partially purified rat brain endothelial Acsl, maximum inhibition by triacsin C was only 82 ± 2%. Solubilized human coronary endothelial cells (HCEC) treated with triacsin C for one minute lost about 86 ± 2.6% of their activity, without further decline as triacsin C exposure time increased. HCEC were treated with 5 μM triacsin C for up to 8 hours, then washed, solubilized and assayed for Acsl activity. Activity in treated cells declined with a half‐time of 19 ± 2.9 minutes. HCEC pre‐treated with triacsin C for 2 hours were washed, re‐fed, and allowed to recover. At 24 hours post‐treatment, activity was only about 39 ± 5% of that of untreated HCEC. After 2 hours triacsin C treatment and 2 hours recovery, HCEC were exposed to [14C]‐palmitic acid for 2 hours. Radioactivity was 15 ± 5.7% of control in the fatty acyl CoA fraction, and 39 ± 2.6% of control in total extractable lipids. The weight of total extractable lipids (μg/well) was 44 ± 2.3 for control and 43 ± 4.6 for treated HCEC (not significant). These data indicate that triacsin C is likely a partial competitive inhibitor of Acsl in vitro and may be an irreversible inhibitor in situ. Supported by AHA 06552254 and NIH R21AG028901.