Effect of fumonisin B-1 on protein and lipid synthesis in primary rat hepatocytes
Effect of fumonisin B-1 on protein and lipid synthesis in primary rat hepatocytes
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DOI：
10.1016/0278-6915(96)00107-x
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发表时间：
1996-04-01
影响因子：
4.3
通讯作者：
Swanevelder, S
中科院分区：
文献类型：
--
作者：
Gelderblom, WCA;Smuts, CM;Swanevelder, S
观察伏马菌素B-1(FB1)对大鼠原代肝细胞蛋白质和脂肪合成的影响。FB1在无毒(150mU)或细胞毒性(500mM)浓度下均不影响[H-3]亮氨酸掺入肝细胞，提示原激肽合成不受影响。然而，FB1显著(P<；0.01至P<；0.0001)抑制肝细胞培养中[C-14]棕榈酸的掺入，这意味着脂质合成发生了改变。在两种FB1浓度下，三酰甘油(TAG)和鞘磷脂组分的放射性标记掺入显著降低(P<；0.05至P<；0.0001)，而磷脂酰胆碱(PC)和磷脂酰乙醇胺(PEA)的掺入显著增加。[C-14]棕榈酸的掺入模式与处理细胞中磷脂水平的变化非常相似。神经鞘脂鞘氨醇(Sa)在处理细胞中显著增加(P<；0.0001)，但在毒性和非毒性剂量水平之间没有显著差异，这意味着单是Sa水平的增加并不是体外毒性的原因。FB1显著(P<；0.01至P<；0.001)降低了细胞内的游离胆固醇水平，导致PC：胆固醇比率增加，表明有更坚硬的膜结构。随后对PC和中性脂TAG的脂肪酸(FA)谱的研究表明，FB1显著(P<；0.05至P<；0.0001)在两个浓度下增加多不饱和脂肪酸C18：2n-6和C20：4n-6的水平。FB1诱导的细胞膜改变，特别是与主要膜磷脂FA改变有关的改变，以及肝细胞FA含量的改变，可能是解释伏马菌素诱导的原代肝细胞细胞毒效应和改变生长反应的关键事件。(C)1996爱思唯尔科学有限公司。保留所有权利。
The effect of fumonisin B-1 (FB1) on protein and lipid synthesis was evaluated in primary rat hepatocytes. FB1 did not affect incorporation of [H-3]leucine into hepatocytes at either non-toxic (150 mu M) or cytotoxic (500 mu M) concentrations indicating that proc-in synthesis was not affected. However, FB1 significantly (P < 0.01 to P < 0.0001) inhibited incorporation of [C-14]palmitic acid into hepatocyte cultures implying that lipid synthesis was altered. Incorporation of the radiolabel was significantly (P < 0.05 to P < 0.0001) lowered in triacylglycerol (TAG) and sphingomyelin fractions and increased in phosphatidylcholine (PC) and phosphatidylethanolamine (PEA) in both FB1 concentrations. The incorporation pattern of [C-14]palmitic acid closely resembles the changes in phospholipid levels in the treated cells. The sphingolipid, sphinganine (Sa), was significantly (P < 0.0001) increased in treated cells but there was no significant difference between the toxic and non-toxic dose levels implying that the increased Sa level alone is not responsible for the in vitro toxicity. FB1 significantly (P < 0.01 to P < 0.001) decreased the level of free cholesterol within the cell, resulting in an increased PC:cholesterol ratio suggesting a more rigid membrane structure. Subsequent studies on the fatty acid (FA) profiles in PC and the neutral lipid, TAG, indicated that FB1 significantly (P < 0.05 to P < O.0001) increased the levels of the polyunsaturated FAs C18:2n-6 and C20:4n-6 at both concentrations. The FB1-induced changes to cellular membranes, specifically those related to FA changes in the major membrane phospholipids, and the altered FA content of the hepatocytes are likely to be key events in explaining the cytotoxic effects and altered growth responses induced by fumonisins in primary hepatocytes. (C) 1996 Elsevier Science Ltd. All rights reserved.