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Curcumin stimulates exosome/microvesicle release in an in vitro model of intracellular lipid accumulation by increasing ceramide synthesis.
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids ( IF 4.8 ) Pub Date : 2020-01-25 , DOI: 10.1016/j.bbalip.2020.158638
David García-Seisdedos 1 , Bohdan Babiy 2 , Milagros Lerma 1 , María E Casado 3 , Javier Martínez-Botas 3 , Miguel A Lasunción 3 , Óscar Pastor 4 , Rebeca Busto 5
Affiliation  

Curcumin, a hydrophobic polyphenol found in the rhizome of Curcuma longa, has been shown to reduce intracellular lipid accumulation in mouse models of lysosomal storage diseases such as Niemann-Pick type C. Exosomes are small extracellular vesicles secreted by cells in response to changes in intracellular ceramide composition. Curcumin can induce exosome/microvesicle release in cellular models of lipid deposition; however, the mechanism by which curcumin stimulates this release is unknown. In a model of lipid trafficking impairment in C6 glia cells, we show that curcumin stimulated ceramide synthesis by increasing the intracellular concentration of ceramide-dihydroceramide. Ceramide overload increased exosome/microvesicle secretion 10-fold, thereby reducing the concentration of lipids in the endolysosomal compartment. These effects were blocked by inhibitors of serine palmitoyltransferase (myriocin) and ceramide synthase (fumonisin B1). It is concluded that the decrease in intracellular lipid deposition induced by curcumin is mediated by increased ceramide synthesis and exosome/microvesicle release. This action may represent an additional health benefit of curcumin.

中文翻译:

姜黄素通过增加神经酰胺的合成来刺激细胞内脂质蓄积的体外模型中外泌体/微泡的释放。

姜黄素是一种在姜黄根茎中发现的疏水性多酚,已被证明能减少溶酶体贮积病小鼠模型(如C型涅曼-皮克病)的细胞内脂质蓄积。外泌体是细胞响应细胞内变化而分泌的小细胞外囊泡神经酰胺的组成。姜黄素可以在脂质沉积的细胞模型中诱导外泌体/微囊泡的释放。然而,姜黄素刺激这种释放的机制尚不清楚。在C6胶质细胞的脂质运输受损模型中,我们显示姜黄素通过增加神经酰胺-二氢神经酰胺的细胞内浓度刺激神经酰胺合成。神经酰胺超负荷使外泌体/微囊泡分泌增加10倍,从而降低了溶酶体区室中脂质的浓度。这些作用被丝氨酸棕榈酰转移酶(myriocin)和神经酰胺合酶(fumonisin B1)的抑制剂所阻断。结论是姜黄素诱导的细胞内脂质沉积的减少是由神经酰胺合成增加和外来体/微囊泡释放介导的。该作用可能代表姜黄素的其他健康益处。
更新日期:2020-01-26
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