Induction of hepatic acyl-CoA-binding protein and liver fatty acid-binding protein by perfluorodecanoic acid in rats. Lack of correlation with hepatic long-chain acyl-CoA levels.
Induction of hepatic acyl-CoA-binding protein and liver fatty acid-binding protein by perfluorodecanoic acid in rats. Lack of correlation with hepatic long-chain acyl-CoA levels.
复制标题
全氟癸酸诱导大鼠肝酰辅酶A结合蛋白和肝脂肪酸结合蛋白。
DOI：
10.1016/0006-2952(94)90366-2
复制
发表时间：
1994
影响因子：
5.8
通讯作者：
Peterson,RE
中科院分区：
文献类型：
--
作者：
Sterchele,PF;VandenHeuvel,JP;Davis2nd,JW;Shrago,E;Knudsen,J;Peterson,RE
肝脏脂肪酸结合蛋白（L-FABP）和酰基辅酶a结合蛋白（ACBP）分别参与肝脏脂肪酸和脂肪酰基辅酶a酯的细胞内运输和区隔化。这两种蛋白都是由强效过氧化物酶体增殖剂全氟烷酸（PFDA）在大鼠肝脏中诱导产生的。虽然人们认为过氧化物酶体增殖体激活受体可能通过诱导应答基因介导对过氧化物酶体增殖体的反应，但该受体的配体尚不清楚。我们假设PFDA诱导大鼠肝脏中L-FABP和ACBP是继发于长链酰基辅酶a酯的积累。然而，PFDA对肝脏长链酰基辅酶a、L-FABP或ACBP浓度的剂量效应和时间过程效应均未证实这一假设。在一项剂量反应研究中，PFDA在20-50 mg/kg的剂量范围内增加了肝脏长链酰基辅酶a浓度（治疗后7天），而在20-65 mg/kg的更宽剂量范围内增加了ACBP和L-FABP。在时间过程研究中，PFDA治疗（50 mg/kg）从治疗后第3天开始升高肝脏长链酰基辅酶a酯，但从第2天开始肝脏L-FABP浓度升高，直到第7天才诱导ACBP。为了确定在其他条件下肝脏长链酰基辅酶a浓度的增加与肝脏L-FABP和ACBP浓度的增加之间是否存在这种解离，我们使用禁食24-48小时的对照大鼠。与PFDA治疗相比，禁食提高了肝脏长链酰基辅酶a水平，但没有诱导L-FABP和ACBP。我们得出结论，pfda处理的大鼠肝脏长链酰基辅酶a浓度升高并不是过氧化物酶体增殖物诱导L-FABP或ACBP的主要因素。一种更合理的机制是PFDA通过直接激活过氧化物酶体增殖体受体而不是通过长链酰基辅酶A酯间接激活L-FABP和ACBP。
Liver fatty acid-binding protein (L-FABP) and acyl-CoA-binding protein (ACBP) are involved in the intracellular trafficking and compartmentalization of fatty acids and fatty acyl-CoA esters, respectively, in the liver. Both proteins are induced in rat liver by the potent peroxisome proliferator perfluorodecanoic acid (PFDA). While it is believed that the peroxisome proliferator-activated receptor may mediate the responses to peroxisome proliferators by inducing responsive genes, the ligand(s) of this receptor remains unknown. We hypothesized that induction of L-FABP and ACBP in rat liver by PFDA is secondary to accumulation of long-chain acyl-CoA esters. However, neither dose-response nor time-course effects of PFDA on hepatic long-chain acyl-CoA, L-FABP, or ACBP concentrations confirmed this hypothesis. In a dose-response study, PFDA increased hepatic long-chain acyl-CoA concentrations (7 days after treatment) over the dose range of 20–50 mg/kg, whereas it increased ACBP and L-FABP over the wider dose range of 20–65 mg/kg. In the time-course study, PFDA treatment (50 mg/kg) elevated long-chain acyl-CoA esters in the liver beginning on day 3 post-treatment, yet hepatic L-FABP concentrations were increased earlier beginning on day 2 and ACBP was not induced until day 7. To determine if this dissociation of increases in hepatic long-chain acyl-CoA concentrations from increases in hepatic L-FABP and ACBP concentrations could be demonstrated under other conditions, control rats fasted for 24–48 hr were used. Fasting increased hepatic long-chain acyl-CoA levels to a greater extent than PFDA treatment, yet neither L-FABP nor ACBP was induced. We conclude that elevated concentrations of hepatic long-chain acyl-CoAs in PFDA-treated rats are not a major contributor to the induction of L-FABP or ACBP by peroxisome proliferators. A more plausible mechanism is that PFDA induces L-FABP and ACBP by activating the peroxisome proliferator receptor directly rather than indirectly through long-chain acyl-CoA esters.