2005 Fiscal Year Final Research Report Summary
Possibility of disease prevention by regulating fatty acid nutrition
| Project/Area Number |
16500511
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Eating habits, studies on eating habits
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| Research Institution | Hyogo University of Teacher Education |
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Principal Investigator |
KISHIDA Etsu Hyogo University of Teacher Education, Graduate School of Education, Associate Professor, 学校教育研究科, 助教授 (70214773)
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| Co-Investigator(Kenkyū-buntansha) |
MASUZAWA Yasuo Hyogo University of Teacher Education, Graduate School of Education, Professor, 学校教育研究科, 教授 (30119622)
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| Project Period (FY) |
2004 – 2005
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| Keywords | fatty acid / cell death / docosahexaenoic acid / necrosis / phospholipid / tumor necrosis factor / apoptosis |
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| Research Abstract |
Tumor necrosis factor (TNF) is a major pro-inflammatory cytokine with a wide variety of functions, one of which is induction of cell death including apoptosis and necrosis. In this study, we explored effects of docosahexaenoic acid (DHA) and other polyunsaturated fatty acids (PUFAs) on TNF-induced cell death.
The effect of preincubation with DHA on cell death was examined using various cultured cells, and compared with the cases of other fatty acids supplementation. Preincubation of cells with DHA for 24 h enriched DHA in cellular phospholipids. DHA showed the distinct ability to reduce TNF-induced apoptosis of U937 cells, but this was not the case in the supplementation of eicosapentaenoic acid (EPA) and arachidonic acid (AA). The inhibition of apoptosis was accompanied by enrichment of DHA in membrane phospholipids, indicating that DHA exerted its inhibitory activity after being incorporated into the phospholipids.
In L929 cells, TNF can induce necrosis, another mode of cell death, and DHA treatment could also reduce this type of cell death. Unlike the case of U937 cell apoptosis, AA significantly attenuated L929 cell necrosis, and 20:3(n-6) or 22:4(n-6) showed similar or less activity, respectively. The order of effective PUFA activity was DHA>docosapentaenoic acid (n-3, DPA)【greater than or equal】EPA>AA【approximately equal】20:3(n-6)【greater than or equal】22:4(n-6). Fatty acid analysis of membrane phospholipids suggested that attenuation of TNF-induced necrosis is mainly attributable to the enrichment of three kinds of PUFAs, i.e. DHA, DPAn-3 or AA, in phospholipids. Among these fatty acids, DHA was the most effective in the reduction of L929 necrosis as observed in the case of U937 apoptosis.
In summary, DHA-enriched membranes can protect cell irrespective of death modes and membranous DHA may abrogate the death signaling common to necrosis and apoptosis.
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