Fish oil nano-emulsion kills macrophage: Ferroptosis triggered by catalase-catalysed superoxide eruption

鱼油纳米乳液杀死巨噬细胞:过氧化氢酶催化的超氧化物喷发引发铁死亡

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作者:Guanzhen Gao, Jingru Zhou, Huiqin Wang, Lijing Ke, Jianwu Zhou, Yanan Ding, Wei Ding, Suyun Zhang, Pingfan Rao

Abstract

Fish oil is increasingly utilised in the form of nano-emulsion as a nutrient and function fortifier. The nano-emulsions exceptionally high content of polyunsaturated fatty acids and electron donors at the oil/water interface provide an ideal site of the redox reaction. Here we report that a vigorous superoxide production in the fish oil nano-emulsion was catalysed by mammalian catalase in acellular and cellular systems. The resulting superoxide increased cytosolic reactive oxygen species (ROS) and membrane lipid peroxidation of murine macrophage, which eventually causes fatal oxidative damages. Cell death, was significantly inhibited by a catalase-specific inhibitor 3-Amino-1,2,4-triazole (3-AT), was via ferroptosis and not apoptosis. The ferroptosis was independent of free iron or glutathione peroxidase suppression. Our findings discovered a hidden health risk of the widely acclaimed fish oil emulsion, suggesting a novel cellular damage mechanism caused by dietary unsaturated fats on the alimentary tract mucosa.

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