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Hydroxyoctadecadienoic acids regulate apoptosis in human THP-1 cells in a PPARγ-dependent manner

Vangaveti, Venkat N., Shashidhar, Venkatesh M., Rush, Catherine, Malabu, Usman H., Rasalam, Roy R., Collier, Fiona, Baune, Bernhard T. and Kennedy, Richard L. 2014, Hydroxyoctadecadienoic acids regulate apoptosis in human THP-1 cells in a PPARγ-dependent manner, Lipids, vol. 49, no. 12, pp. 1181-1192, doi: 10.1007/s11745-014-3954-z.

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Title Hydroxyoctadecadienoic acids regulate apoptosis in human THP-1 cells in a PPARγ-dependent manner
Author(s) Vangaveti, Venkat N.
Shashidhar, Venkatesh M.
Rush, Catherine
Malabu, Usman H.
Rasalam, Roy R.
Collier, Fiona
Baune, Bernhard T.
Kennedy, Richard L.
Journal name Lipids
Volume number 49
Issue number 12
Start page 1181
End page 1192
Publisher Springer
Place of publication Heidelberg , Germany
Publication date 2014-12
ISSN 0024-4201
1558-9307
Keyword(s) Apoptosis
Macrophages
Monocytes
Oxidized lipids
Summary Macrophage apoptosis, a key process in atherogenesis, is regulated by oxidation products, including hydroxyoctadecadienoic acids (HODEs). These stable oxidation products of linoleic acid (LA) are abundant in atherosclerotic plaque and activate PPARγ and GPR132. We investigated the mechanisms through which HODEs regulate apoptosis. The effect of HODEs on THP-1 monocytes and adherent THP-1 cells were compared with other C18 fatty acids, LA and α-linolenic acid (ALA). The number of cells was reduced within 24 hours following treatment with 9-HODE (p < 0.01, 30 μM) and 13 HODE (p < 0.01, 30 μM), and the equivalent cell viability was also decreased (p < 0.001). Both 9-HODE and 13-HODE (but not LA or ALA) markedly increased caspase-3/7 activity (p < 0.001) in both monocytes and adherent THP-1 cells, with 9-HODE the more potent. In addition, 9-HODE and 13-HODE both increased Annexin-V labelling of cells (p < 0.001). There was no effect of LA, ALA, or the PPARγ agonist rosiglitazone (1μM), but the effect of HODEs was replicated with apoptosis-inducer camptothecin (10μM). Only 9-HODE increased DNA fragmentation. The pro-apoptotic effect of HODEs was blocked by the caspase inhibitor DEVD-CHO. The PPARγ antagonist T0070907 further increased apoptosis, suggestive of the PPARγ-regulated apoptotic effects induced by 9-HODE. The use of siRNA for GPR132 showed no evidence that the effect of HODEs was mediated through this receptor. 9-HODE and 13-HODE are potent—and specific—regulators of apoptosis in THP-1 cells. Their action is PPARγ-dependent and independent of GPR132. Further studies to identify the signalling pathways through which HODEs increase apoptosis in macrophages may reveal novel therapeutic targets for atherosclerosis.
Language eng
DOI 10.1007/s11745-014-3954-z
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 920102 Cancer and Related Disorders
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2014, Springer
Persistent URL http://hdl.handle.net/10536/DRO/DU:30067395

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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Created: Mon, 08 Dec 2014, 14:01:28 EST

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