Ethanol stimulates leucine uptake by rat fetal hepatocytes via trans-stimulation.
Ethanol stimulates leucine uptake by rat fetal hepatocytes via trans-stimulation.
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乙醇通过反式刺激刺激大鼠胎儿肝细胞对亮氨酸的摄取。
DOI：
10.1152/ajpgi.1989.256.2.g384
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Schenker,S
中科院分区：
文献类型：
--
作者：
Henderson,GI;Frosto,TA;Heitman,DW;Schenker,S
先前的研究表明，培养的大鼠胎儿肝细胞暴露于乙醇会增加α-氨基异丁酸和环亮氨酸的钠依赖性转运。使用亮氨酸 (Leu) 作为探针，我们现在表明这是 L 系统内向通量反式刺激的反映。 Leu 的转运完全不依赖于钠，并且可被 β-2-氨基双环(2,2,1)-庚烷-2-羧酸抑制。摄取动力学表明有两个组成部分，可能是成人肝细胞报告的 L1 和 L2 系统。低亲和力 Km 在 0.5 mM 范围内，而高亲和力 Km 为该值的 2%。在最佳生长条件下，大约 65% 的 Leu 由后一个系统运输。 Leu 负载显示出强烈的双向交换，刺激初始 Leu 吸收 66%。与无外部 Leu 相比，5 x 10(-3) M Leu 的外部定向运输增强了 2.9 倍。暴露于乙醇 (2 mg/ml) 24 小时可使 Leu 摄取增加高达 100%，这种效果可以通过细胞复制停滞来模拟。这两种增强的速率都可以通过氨基酸消耗来逆转，反映了诱导亮氨酸摄取反式刺激的细胞内氨基酸累积。通过加载浓度不断增加的亮氨酸，复制细胞中的摄取也得到增强。
Prior studies showed that exposure of cultured rat fetal hepatocytes to ethanol increased sodium-independent transport of alpha-amino-isobutyric acid and cycloleucine. Using leucine (Leu) as a probe, we now show that this is a reflection of trans-stimulation of system L inward flux. Transport of Leu was entirely sodium independent and beta-2-aminobicyclo(2,2,1)-heptane-2-carboxylic acid inhibitable. Uptake kinetics indicated two components, likely systems L1 and L2 reported for the adult hepatocyte. The low-affinity Km was in the 0.5 mM range, whereas the high-affinity Km was 2% of that value. Under optimal growth conditions, approximately 65% of the Leu was transported by the latter system. Strong bidirectional exchange was shown with Leu loading, stimulating initial Leu uptake by 66%. Externally directed transport was enhanced 2.9 times against 5 x 10(-3) M Leu vs. no external Leu. A 24-h exposure to ethanol (2 mg/ml) increased Leu uptake by up to 100%, an effect that could be mimicked by arrested cell replication. Both enhanced rates could be reversed by amino acid depletion, reflecting intracellular amino accrual that induced trans-stimulation of Leu uptake. Enhanced uptake was also reproduced in replicating cells by loading with increasing concentrations of Leu.