INSULIN-LIKE GROWTH-FACTOR-I STIMULATES AMINO-ACID-UPTAKE BY THE CULTURED HUMAN PLACENTAL TROPHOBLAST
INSULIN-LIKE GROWTH-FACTOR-I STIMULATES AMINO-ACID-UPTAKE BY THE CULTURED HUMAN PLACENTAL TROPHOBLAST
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DOI：
10.1002/jcp.1041650111
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发表时间：
1995-10-01
影响因子：
5.6
通讯作者：
KARL, PI
中科院分区：
文献类型：
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作者：
KARL, PI
已知人胎盘的氨基酸摄取通过几种转运机制发生。然而，细胞外因子的调节受到的关注相对较少。本实验室最近的一份报告描述了胰岛素刺激培养的人胎盘滋养层细胞摄取α-氨基异丁酸（AIB）的特征。本研究探讨了胰岛素样生长因子-1（IGF-1）对培养的人胎盘滋养层细胞摄取AIB的影响。NaI依赖的AIB摄取显着刺激ICF-I在一个时间依赖性的方式，早在激素暴露后30分钟。最大效应是在连续暴露于ICF-I 2-4小时时，并且刺激依赖于在50 ng.ml（-1）接近最大刺激的IGF-1浓度。增加α-（甲氨基）异丁酸（MeAIB）浓度可抑制AIB摄取。约75%的基础（未受刺激）Na+依赖的AIB摄取被MeAIB抑制。MeAIB完全抑制IGF-1刺激的高于基础AIB摄取的增量。IGF-1增加最大摄取速度，但不增加Km。使用等摩尔浓度，IGF-1的刺激作用大于IGF-2。IGF-1而非胰岛素的刺激被抗ICF-1受体抗体抑制，表明通过IGF-1受体介导。H7是一种丝氨酸-苏氨酸激酶的非特异性抑制剂，可抑制IGF-1依赖的AIB摄取刺激。此外，calphostin C（蛋白激酶C的特异性抑制剂），而不是H89（蛋白激酶A的特异性抑制剂），抑制IGF-1的作用。这项研究进一步表征了人胎盘滋养层细胞对氨基酸的摄取，并表明AIB摄取的Na+依赖性组分受到生理浓度IGF-1的刺激。(C)Wiiey-Liss，Inc.
Amino acid uptake by the human placenta is known to occur via several transport mechanisms. However, regulation by extracellular factors has received relatively little attention. A recent report by this laboratory characterized the uptake of alpha-aminoisobutyric acid (AIB) stimulated by insulin in the cultured human placental trophoblast. The current study evaluated the effect of insulin-like growth factor-1 (IGF-1) on AIB uptake in cultured human placental trophoblasts. Nai-dependent AIB uptake was significantly stimulated by ICF-I in a time-dependent manner, as early as 30 min after hormone exposure. The maximum effect was at 2-4 hr of continuous exposure to ICF-I and the stimulation was dependent upon IGF-1 concentration approaching maximal stimulation at 50 ng.ml(-1). AIB uptake was inhibited by increasing concentrations of alpha-(methylamino)isobutyric acid (MeAIB). Approximately 75% of basal (unstimulated) Na+-dependent AIB uptake was inhibited by MeAIB. The IGF-l-stimulated increment above basal AIB uptake was completely inhibited by MeAIB. IGF-1 increased the maximum uptake velocity but not Km. Using equimolar concentrations, stimulation was greater with IGF-1 than with IGF-2. Stimulation by IGF-l, but not insulin, was inhibited by anti-ICF-l receptor antibody, indicating mediation via the IGF-1 receptor. H7, a nonspecific inhibitor of serine-threonine kinase, inhibited IGF-1-dependent stimulation of AIB uptake. In addition, calphostin C (a specific inhibitor of protein kinase C), but not H89 (a specific inhibitor of protein kinase A), inhibited the IGF-1 action. This study further characterizes regulated amino acid uptake by the human placental trophoblasts and demonstrates that the Na+-dependent component of AIB uptake is stimulated by physiologic concentrations of IGF-1. (C) 1995 Wiiey-Liss, Inc.