In:
European Journal of Biochemistry, Wiley, Vol. 267, No. 13 ( 2000-07), p. 4063-4067
Abstract:
Phytanic acid (3,7,11,15‐tetramethylhexadecanoic acid) is a branched‐chain fatty acid present in various dietary products such as milk, cheese and fish. In patients with Refsum disease, accumulation of phytanic acid occurs due to a deficiency of phytanoyl‐CoA hydroxylase, a peroxisomal enzyme containing a peroxisomal targeting signal 2. Recently, phytanoyl‐CoA hydroxylase cDNA has been isolated and functional mutations have been identified. As it has been shown that phytanic acid activates the nuclear hormone receptors peroxisome proliferator‐activated receptor (PPAR)α and all three retinoid X receptors (RXRs), the intracellular concentration of this fatty acid should be tightly regulated. When various cell lines were grown in the presence of phytanic acid, the activity of phytanoyl‐CoA hydroxylase increased up to four times, depending on the particular cell type. In one cell line, HepG2, no induction of phytanoyl‐CoA hydroxylase activity was observed. After addition of phytanic acid to COS‐1 cells, an increase in phytanoyl‐CoA hydroxylase activity was observed within 2 h, indicating a quick cell response. No stimulation of phytanoyl‐CoA hydroxylase was observed when COS‐1 cells were grown in the presence of clofibric acid, 9‐ cis ‐retinoic acid or both ligands together. This indicates that the activation of phytanoyl‐CoA hydroxylase is not regulated via PPARα or RXR. However, stimulation of PPARα and all RXRs by clofibric acid and 9‐ cis ‐retinoic acid was observed in transient transfection assays. These results suggest that the induction of phytanoyl‐CoA hydroxylase by phytanic acid does not proceed via one of the nuclear hormone receptors, RXR or PPARα.
Type of Medium:
Online Resource
ISSN:
0014-2956
,
1432-1033
DOI:
10.1046/j.1432-1327.2000.01451.x
Language:
English
Publisher:
Wiley
Publication Date:
2000
detail.hit.zdb_id:
1398347-7
detail.hit.zdb_id:
2172518-4
SSG:
12
