Modulation of key lipid raft constituents in primary rat hepatocytes by fumonisin B1 - Implications for cancer promotion in the liver
Modulation of key lipid raft constituents in primary rat hepatocytes by fumonisin B1 - Implications for cancer promotion in the liver
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DOI：
10.1016/j.fct.2018.03.004
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发表时间：
2018-05-01
影响因子：
4.3
通讯作者：
Gelderblom, W. C. A.
中科院分区：
文献类型：
--
作者：
Burger, H-M;Abel, S.;Gelderblom, W. C. A.
伏马菌素B-1(Fumonisin B-1，FB1)是一种2B组天然致癌真菌毒素，经FbI细胞毒浓度(250 MU M)作用后，可调节原代肝细胞脂筏的脂和脂肪酸成分。在筏上观察到的主要影响包括显著增加(p<；0.05)RAFT胆固醇(CHOL)和甘油磷脂(如磷脂酰乙醇胺(PE))，而神经鞘磷脂(SM)减少(p<；0.05)。脂质成分的改变导致重要的膜流动性参数的破坏，表现为磷脂酰胆碱(PC)/PE和PC/(PE+SM)比值的降低(p<；0.05)，而Chol/PL(PL=PC+PE)比值的升高(p<；0.05)，表明脂筏的刚性和完整性得以保存。观察到的脂肪酸变化包括C18：2 omega-6，C20：3 omega-6，C20：4 omega-6，C22：4 omega-6，C22：5 omega-3和C22：6 omega-3显著增加(p<；0.05)，总co-6和co-3多不饱和脂肪酸(PUFAs)增加。调节PE中FA的含量，特别是C20：4 omega-6 PC/PE比率和PUFA水平，以及Chol和SM的变化，是调节脂筏完整性和功能的关键决定因素。在原代肝细胞中，这些变化与抑制细胞增殖和诱导细胞凋亡有关。在肝脏促癌过程中，FB1通过调节脂筏和不同靶点的正常肝细胞和癌前肝细胞的细胞存活指数，提出了一种造脂机制。
Fumonisin B-1 (FB1) a group 2B natural occurring carcinogenic mycotoxin, modulated lipid and fatty acid (FA) constituents of lipid rafts isolated from primary hepatocytes following exposure to a cytotoxic concentration of FB I (250 mu M). The major effects observed in rafts, included a significant (p < 0.05) increase in raft cholesterol (CHOL) and glycerophospholipid such as phosphatidylethanolamine (PE), whereas sphingomyelin (SM) decreased (p < 0.05). Changes in lipid constituents resulted in the disruption of important membrane fluidity parameters represented as a decreased (p < 0.05) in the phosphatidylcholine (PC)/PE and PC/(PE + SM) ratios and an increase (p < 0.05) in the CHOL/PL (PL =PC + PE) ratio, suggesting the preservation of lipid raft rigidity and integrity. Observed FA changes in the raft PE fraction included a significant (p < 0.05) increase in C18:2 omega-6, C20:3 omega-6, C20:4 omega-6, C22:4 omega-6, C22:5 omega-3 and C22:6 omega-3, with an increase in total co-6 and co-3 polyunsaturated fatty acids (PUFAs). Modulation of the FA content in PE, specifically the C20:4 omega-6 PC/PE ratio and PUFA levels, together with changes in CHOL and SM are key determinants regulating the integrity and function of lipid rafts. In primary hepatocytes these changes are associated with the inhibition of cell proliferation and induction of apoptosis. A lipogenic mechanism is proposed whereby FB1 modulates lipid rafts and differentially target cell survival indices of normal and preneoplastic hepatocytes during cancer promotion in the liver.