Verstraeten Sandra V, Jaggers Grayson K, Fraga Cesar G, Oteiza Patricia I
Department of Biological Chemistry and IQUIFIB (UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
Biochim Biophys Acta. 2013 Nov;1828(11):2646-53. doi: 10.1016/j.bbamem.2013.07.023. Epub 2013 Jul 27.
Large procyanidins (more than three subunits) are not absorbed at the gastrointestinal tract but could exert local effects through their interactions with membranes. We previously showed that hexameric procyanidins (Hex), although not entering cells, interact with membranes modulating cell signaling and fate. This paper investigated if Hex, as an example of large procyanidins, can selectively interact with lipid rafts which could in part explain its biological actions. This mechanism was studied in both synthetic membranes (liposomes) and Caco-2 cells. Hex promoted Caco-2 cell membrane rigidification and dehydration, effects that were abolished upon cholesterol depletion with methyl-β-cyclodextrin (MCD). Hex prevented lipid raft structure disruption induced by cholesterol depletion/redistribution by MCD or sodium deoxycholate. Supporting the involvement of cholesterol-Hex bonding in Hex interaction with lipid rafts, the absence of cholesterol markedly decreased the capacity of Hex to prevent deoxycholate- and Triton X-100-mediated disruption of lipid raft-like liposomes. Stressing the functional relevance of this interaction, Hex mitigated lipid raft-associated activation of the extracellular signal-regulated kinases (ERK) 1/2. Results support the capacity of a large procyanidin (Hex) to interact with membrane lipid rafts mainly through Hex-cholesterol bondings. Procyanidin-lipid raft interactions can in part explain the capacity of large procyanidins to modulate cell physiology.
大原花青素（超过三个亚基）在胃肠道中不被吸收，但可通过与膜的相互作用发挥局部效应。我们之前表明，六聚体原花青素（Hex）虽不进入细胞，但可与膜相互作用，调节细胞信号传导和细胞命运。本文研究了作为大原花青素示例的Hex是否能选择性地与脂筏相互作用，这可能部分解释其生物学作用。该机制在合成膜（脂质体）和Caco - 2细胞中均有研究。Hex促进Caco - 2细胞膜硬化和脱水，用甲基 - β - 环糊精（MCD）耗尽胆固醇后，这些效应消失。Hex可防止由MCD或脱氧胆酸钠导致的胆固醇耗尽/重新分布所引起的脂筏结构破坏。支持胆固醇 - Hex键参与Hex与脂筏相互作用的是，缺乏胆固醇显著降低了Hex防止脱氧胆酸盐和 Triton X - 100介导的类脂筏脂质体破坏的能力。强调这种相互作用的功能相关性的是，Hex减轻了脂筏相关的细胞外信号调节激酶（ERK）1/2的激活。结果支持大原花青素（Hex）主要通过Hex - 胆固醇键与膜脂筏相互作用的能力。原花青素 - 脂筏相互作用可部分解释大原花青素调节细胞生理的能力。
