In:
Lipids, Wiley, Vol. 44, No. 8 ( 2009-08), p. 673-683
Abstract:
The SREBP‐2 transcription factor is mainly activated by low cellular cholesterol levels. However, other factors may also cause SREBP‐2 activation. We have previously demonstrated activation of SREBP‐2 by the polyunsaturated fatty acid docosahexaenoic acid (DHA) in SW620 colon cancer cells. Despite activation of SREBP‐2, only a few target genes were induced and cholesterol biosynthesis was reduced. In the present study, gene expression analysis at early time points verified the previously observed SREBP‐2 target gene expression pattern. Activation of SREBP‐2 using siRNAs targeting Niemann Pick C1 protein (NPC1) led to increased expression of all SREBP target genes examined, indicating that activation of some SREBP‐2 target genes is inhibited during DHA‐treatment. Cholesterol supplementation during DHA treatment did not abolish SREBP‐2 activation. We also demonstrate that activation of SREBP‐2 is independent of ER stress and eIF2α phosphorylation, which we have previously observed in DHA‐treated cells. Thapsigargin‐induced ER stress repressed expression of SREBP‐2 target genes, but with a different pattern than observed in DHA‐treated cells. Moreover, oleic acid (OA) treatment, which does not induce ER stress in SW620 cells, led to activation of SREBP‐2 and induced a target gene expression pattern similar to that of DHA‐treated cells. These results indicate that DHA and OA may activate SREBP‐2 and inhibit activation of SREBP‐2 target genes through a mechanism independent of cholesterol level and ER stress.
Type of Medium:
Online Resource
ISSN:
0024-4201
,
1558-9307
DOI:
10.1007/s11745-009-3324-4
Language:
English
Publisher:
Wiley
Publication Date:
2009
detail.hit.zdb_id:
2030265-4
SSG:
12
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