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Biochem Biophys Res Commun. 2014 Jan 17;443(3):991-6. doi: 10.1016/j.bbrc.2013.12.085. Epub 2013 Dec 19.

4-Hydroxy hexenal derived from dietary n-3 polyunsaturated fatty acids induces anti-oxidative enzyme heme oxygenase-1 in multiple organs.

Author information

1
Department of Medicine, Shiga University of Medical Science, Seta Tsukinowa-Cho, Otsu, Shiga 520-2192, Japan; Osaka Laboratory, JCL Bioassay Corporation, 5-16-26, Minamisuita, Suita-shi, Osaka 564-0043, Japan.
2
Department of Medicine, Shiga University of Medical Science, Seta Tsukinowa-Cho, Otsu, Shiga 520-2192, Japan. Electronic address: morino@belle.shiga-med.ac.jp.
3
Department of Medicine, Shiga University of Medical Science, Seta Tsukinowa-Cho, Otsu, Shiga 520-2192, Japan.
4
Osaka Laboratory, JCL Bioassay Corporation, 5-16-26, Minamisuita, Suita-shi, Osaka 564-0043, Japan.
5
Department of Diabetes and Endocrine Medicine, Division of Human and Environmental Sciences, Kagoshima University, Graduate School of Medical and Dental Sciences, Kagoshima, Japan.

Abstract

It has recently been reported that expression of heme oxygenase-1 (HO-1) plays a protective role against many diseases. Furthermore, n-3 polyunsaturated fatty acids (PUFAs) were shown to induce HO-1 expression in several cells in vitro, and in a few cases also in vivo. However, very few reports have demonstrated that n-3 PUFAs induce HO-1 in vivo. In this study, we examined the effect of fish-oil dietary supplementation on the distribution of fatty acids and their peroxidative metabolites and on the expression of HO-1 in multiple tissues (liver, kidney, heart, lung, spleen, intestine, skeletal muscle, white adipose, brown adipose, brain, aorta, and plasma) of C57BL/6 mice. Mice were divided into 4 groups, and fed a control, safflower-oil, and fish-oil diet for 3 weeks. One group was fed a fish-oil diet for just 1 week. The concentration of fatty acids, 4-hydroxy hexenal (4-HHE), and 4-hydroxy nonenal (4-HNE), and the expression of HO-1 mRNA were measured in the same tissues. We found that the concentration of 4-HHE (a product of n-3 PUFAs peroxidation) and expression of HO-1 mRNA were significantly increased after fish-oil treatment in most tissues. In addition, these increases were paralleled by an increase in the level of docosahexaenoic acid (DHA) but not eicosapentaenoic acid (EPA) in each tissue. These results are consistent with our previous results showing that DHA induces HO-1 expression through 4-HHE in vascular endothelial cells. In conclusion, we hypothesize that the HO-1-mediated protective effect of the fish oil diet may be through production of 4-HHE from DHA but not EPA in various tissues.

KEYWORDS:

4-Hydroxy hexenal; Docosahexaenoic acid (DHA); Heme oxygenase-1; Nuclear factor erythroid 2-related factor 2 (Nrf2); n-3 Polyunsaturated fatty acids (PUFAs)

PMID:
24361890
DOI:
10.1016/j.bbrc.2013.12.085
[Indexed for MEDLINE]
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