THYROID-HORMONE RECEPTORS AND STIMULATION OF ANGIOTENSINOGEN PRODUCTION IN HEPG2 CELLS
THYROID-HORMONE RECEPTORS AND STIMULATION OF ANGIOTENSINOGEN PRODUCTION IN HEPG2 CELLS
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DOI：
10.1007/bf02630890
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发表时间：
1991-01-01
期刊：
影响因子：
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通讯作者：
CORVOL, P
中科院分区：
文献类型：
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作者：
DARBY, IA;BOUHNIK, J;CORVOL, P
在无血清培养基中研究了3,5，-3′-三碘- l -甲状腺原氨酸（T3）对HepG2细胞血管紧张素原生成的结合特性及影响。使用[I-125]T3对完整细胞和部分纯化的分离细胞核进行结合。Scatchard图显示一类高亲和力结合位点，K(d)约为80 pmol/l。最大结合计算表明，HepG2在每个细胞中大约有1000个结合位点。未标记的T3和T4在完整HepG2上竞争结合位点，对[I-125]T3结合的抑制作用分别为约3.0和38.0 pmol/l，抑制率为50%。HepG2在无血清培养基中血管紧张素原产生呈剂量依赖性增加，在10(-5)mol/l时最大（增加两倍/10(6)个细胞/24 h）， EC50约为5.0 × 10(-8) mol/l。T3在24 h后也产生了剂量依赖性的DNA增加，与施加T3高度相关（r = 0.88, P < 0.01）。综上所述，本研究表明HepG2对T3具有特异性的高亲和力结合位点，并且T3刺激这些细胞的血管紧张素原产生和DNA合成。
Binding characteristics and effects of 3,5,-3'-triiodo-L-thyronine (T3) on angiotensinogen production in HepG2 were studied in serum-free medium. Binding was performed on intact cells and on partially purified isolated nuclei using [I-125]T3. Scatchard plots revealed one class of high affinity binding sites with a K(d) of approximately 80 pmol/liter. Calculation of maximum binding showed that HepG2 possess approximately 1000 binding sites per cell. Unlabeled T3 and T4 competed for binding sites on intact HepG2 with 50% inhibition of [I-125]T3 binding at approximately 3.0 and 38.0 pmol/liter, respectively. The HepG2 showed a dose-dependent incresae in angiotensinogen production in serum-free medium which was maximal at 10(-5) mol/liter (two-fold increase/10(6) cells/24 h) and had an EC50 of approximately 5.0 X 10(-8) mol/liter. T3 also produced after 24 h a dose-dependent increase in DNA highly correlated with T3 applied (r = 0.88, P < 0.01). In conclusion, this study shows that HepG2 possess specific high affinity binding sites for T3 and that T3 stimulates angiotensinogen production and DNA synthesis in these cells.