脂肪酸配体通过改变过氧化物酶体增殖物激活受体γ三维构象调节RBL-2H3细胞脱颗粒

Fatty acid ligand binding regulates RBL-2H3 degranulation by changing the three-dimensional conformation of peroxisome proliferators-activated receptor γ

中文关键词:  食物过敏  PPARγ  脂肪酸  分子对接  脱颗粒

英文关键词:food allergies  peroxisome proliferators-activated receptor γ  fatty acids  molecular docking  degranulation

中文摘要:

      目的 研究各种脂肪酸与效应细胞脱颗粒程度之间的关系。方法 采用分子对接技术, 将月桂酸、硬脂酸、油酸、亚油酸和α-亚麻酸作为配体与过氧化物酶体增殖物激活受体γ (peroxisome proliferators-activated receptor γ, PPARγ)对接, 预测其对效应细胞脱颗粒的影响。基于RBL-2H3模型, 以β-氨基己糖苷酶的释放量来评估这些脂肪酸能否作为PPARγ的天然配体, 调节效应细胞脱颗粒。结果 5种脂肪酸对RBL-2H3脱颗粒有不同影响。月桂酸显著促进脱颗粒, 而油酸和α-亚麻酸抑制脱颗粒程度。硬脂酸和亚油酸则对脱颗粒程度无显著影响。结论 脂肪酸作为天然配体, 不同的结合深度, 使PPARγ呈现出不同的三维构象, 从而产生对激活因子和抑制因子不同的亲和力, 以调节肥大细胞或嗜碱性粒细胞脱颗粒的程度。这为通过饮食干预来改善食物过敏提供了可能性。

英文摘要:

      Objective To investigate the relationship between various fatty acids and the degree of degranulation of effector cells. Methods Lauric acid, stearic acid, oleic acid, linoleic acid and α-linolenic acid were docked with peroxisome proliferators-activated receptor γ (PPARγ) as ligands by molecular docking technology, and their effects on effector cell degranulation were predicted. RBL-2H3 cells are used to verify whether these fatty acids act as natural ligands for PPARγ and to regulate effector cell degranulation. Results Five kinds of fatty acids had a significant effect on RBL-2H3 degranulation. Lauric acid significantly promoted degranulation, and oleic acid and α-linolenic acid inhibited the degree of degranulation. Stearic acid and linoleic acid had no significant effect on the degree of particles. Conclusion Different binding depths of fatty acids as natural ligands in the pocket structure make PPARγ exhibit different three-dimensional conformations, resulting in different affinities for activators and inhibitors to regulate the degree of mast cell or basophil degranulation. This suggests that we may be able to improve our food allergies with dietary interventions.