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Saturated Fatty Acids Induce Ceramide-associated Macrophage Cell Death
Published on: October 31, 2017
Oxidized unsaturated fatty acids induce apoptotic cell death in cultured cells
Katsuya Iuchi1, Mika Ema1, Moe Suzuki1
1Department of Materials and Life Science, Faculty of Science and Technology, Seikei University, Tokyo 180‑8633, Japan.
Abstract:
Polyunsaturated fatty acids are oxidized by non‑enzymatic or enzymatic reactions. The oxidized products are multifunctional. In this study, we investigated how oxidized fatty acids inhibit cell proliferation in cultured cells. We used polyunsaturated and saturated fatty acids, docosahexaenoic acid (DHA; 22:6), eicosapentaenoic acid (EPA; 20:5), linoleic acid (LA; 18:2), and palmitic acid (16:0). Oxidized fatty acids were produced by autoxidation of fatty acids for 2 days in the presence of a gas mixture (20% O2 and 80% N2). We found that oxidized polyunsaturated fatty acids (OxDHA, OxEPA and OxLA) inhibited cell proliferation much more effectively compared with un‑oxidized fatty acids (DHA, EPA and LA, respectively) in THP‑1 (a human monocytic leukemia cell line) and DLD‑1 (a human colorectal cancer cell line) cells. In particular, OxDHA markedly inhibited cell proliferation. DHA has the largest number of double bonds and is most susceptible to oxidation among the fatty acids. OxDHA has the largest number of highly active oxidized products. Therefore, the oxidative levels of fatty acids are associated with the anti‑proliferative activity. Moreover, caspase‑3/7 was activated in the cells treated with OxDHA, but not in those treated with DHA. A pan‑caspase inhibitor (zVAD‑fmk) reduced the cell death induced by OxDHA. These results indicated that oxidized products from polyunsaturated fatty acids induced apoptosis in cultured cells. Collectively, the switch between cell survival and cell death may be regulated by the activity and/or number of oxidized products from polyunsaturated fatty acids.
Insights
Oxidized polyunsaturated fatty acids, especially oxidized docosahexaenoic acid (OxDHA), significantly inhibit cell proliferation by inducing apoptosis. The level of fatty acid oxidation correlates with anti-proliferative activity, highlighting the role of oxidized lipids in cell death regulation.
Area of Science:
- Lipid biochemistry
- Cell biology
- Molecular pharmacology
Background:
- Polyunsaturated fatty acids (PUFAs) undergo oxidation via enzymatic or non-enzymatic pathways, yielding multifunctional products.
- Understanding the biological effects of oxidized fatty acids is crucial for cell signaling and disease research.
Purpose of the Study:
- To investigate the impact of oxidized PUFAs on cell proliferation in cultured cell lines.
- To determine the relationship between the degree of fatty acid oxidation and its anti-proliferative effects.
- To elucidate the mechanism by which oxidized fatty acids induce cell death.
Main Methods:
- Autoxidation of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), linoleic acid (LA), and palmitic acid (PA).
- Treatment of THP-1 and DLD-1 cells with oxidized and un-oxidized fatty acids.
- Assessment of cell proliferation and apoptosis markers, including caspase-3/7 activation.
- Evaluation of cell death inhibition using a pan-caspase inhibitor (zVAD-fmk).
Main Results:
- Oxidized PUFAs (OxDHA, OxEPA, OxLA) exhibited significantly greater inhibition of cell proliferation than their un-oxidized counterparts.
- Oxidized docosahexaenoic acid (OxDHA) demonstrated the most potent anti-proliferative effect.
- OxDHA treatment led to caspase-3/7 activation, indicating apoptosis induction, which was partially blocked by zVAD-fmk.
- Fatty acid oxidative levels correlated directly with anti-proliferative activity.
Conclusions:
- Oxidized polyunsaturated fatty acids, particularly OxDHA, induce apoptosis in cultured cells.
- The anti-proliferative activity of fatty acids is associated with their degree of oxidation.
- The balance between cell survival and cell death may be modulated by the quantity and activity of oxidized PUFA products.
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