Lipotoxic stress alters the membrane lipid profile of extracellular vesicles released by Huh-7 hepatocarcinoma cells.
Lipotoxic stress alters the membrane lipid profile of extracellular vesicles released by Huh-7 hepatocarcinoma cells.
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脂毒性应激改变Huh-7肝癌细胞释放的细胞外囊泡的膜脂质谱。
DOI：
10.1038/s41598-021-84268-9
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发表时间：
2021-02-25
影响因子：
4.6
通讯作者：
Emiliani C
中科院分区：
文献类型：
--
作者：
Buratta S;Shimanaka Y;Costanzi E;Ni S;Urbanelli L;Kono N;Morena F;Sagini K;Giovagnoli S;Romani R;Gargaro M;Arai H;Emiliani C
细胞外囊泡（EV）是众所周知的细胞间通讯介质，在促进肝脏炎症和纤维化（与饱和游离脂肪酸超载引起的肝脂毒性相关事件）中发挥着关键作用。然而，尽管脂质在 EV 膜结构中很重要，进而影响 EV 的生物物理和生物特性，但人们对在这些条件下释放的 EV 的脂质资产知之甚少。在这里，我们分析了肝癌 Huh-7 细胞在补充饱和脂肪酸棕榈酸酯或 Δ9 去饱和酶抑制诱导的膜脂饱和度增加的情况下释放的 EV 的磷脂谱变化，并使用油酸（一种无毒的单不饱和脂肪酸）作为对照。由于膜脂饱和度的增加会诱导内质网 (ER) 应激，我们还分析了用传统 ER 应激诱导剂毒胡萝卜素处理的 Huh-7 细胞释放的 EV 中的磷脂重排。结果表明，脂毒性和/或内质网应激条件不仅诱导细胞膜磷脂重排，而且诱导释放的 EV 重排。因此，细胞膜饱和水平和/或 ER 应激对于确定哪些脂质通过 EV 丢弃至关重要，EV 脂质货物可能有助于区分肝脂质超载和 ER 应激。
Extracellular vesicles (EVs) are well-known mediators in intercellular communication playing pivotal roles in promoting liver inflammation and fibrosis, events associated to hepatic lipotoxicity caused by saturated free fatty acid overloading. However, despite the importance of lipids in EV membrane architecture which, in turn, affects EV biophysical and biological properties, little is known about the lipid asset of EVs released under these conditions. Here, we analyzed phospholipid profile alterations of EVs released by hepatocarcinoma Huh-7 cells under increased membrane lipid saturation induced by supplementation with saturated fatty acid palmitate or Δ9 desaturase inhibition, using oleate, a nontoxic monounsaturated fatty acid, as control. As an increase of membrane lipid saturation induces endoplasmic reticulum (ER) stress, we also analyzed phospholipid rearrangements in EVs released by Huh-7 cells treated with thapsigargin, a conventional ER stress inducer. Results demonstrate that lipotoxic and/or ER stress conditions induced rearrangements not only into cell membrane phospholipids but also into the released EVs. Thus, cell membrane saturation level and/or ER stress are crucial to determine which lipids are discarded via EVs and EV lipid cargos might be useful to discriminate hepatic lipid overloading and ER stress.
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DOI：
10.1073/pnas.1521230113
发表时间：
2016-02-23
影响因子：
11.1
作者：
Kowal, Joanna;Arras, Guillaume;Thery, Clotilde
通讯作者：
Thery, Clotilde
DOI：
10.1016/j.ymeth.2015.04.014
发表时间：
2015-10-01
期刊：
Methods (San Diego, Calif.)
影响因子：
--
作者：
Lydic TA;Townsend S;Adda CG;Collins C;Mathivanan S;Reid GE
通讯作者：
Reid GE
影响因子：
5.2
作者：
Mezzasoma, Letizia;Costanzi, Egidia;Bellezza, Ilaria
通讯作者：
Bellezza, Ilaria
影响因子：
25.7
作者：
Malhi, Harmeet;Kaufman, Randal J.
通讯作者：
Kaufman, Randal J.
影响因子：
6.5
作者：
Leamy, Alexandra K.;Egnatchik, Robert A.;Young, Jamey D.
通讯作者：
Young, Jamey D.