Effects of TCDD and estradiol-17β on the proliferation and Na+/glucose cotransporter in renal proximal tubule cells
Effects of TCDD and estradiol-17β on the proliferation and Na+/glucose cotransporter in renal proximal tubule cells
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DOI：
10.1016/j.tiv.2004.04.011
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发表时间：
2005-02-01
影响因子：
3.2
通讯作者：
Lee, JH
中科院分区：
文献类型：
--
作者：
Han, HJ;Lim, MJ;Lee, JH
TCDD（2，3，7，8-tetrachlorodibenzo-p-dioxin）是一种毒性很高的环境毒物，可改变细胞增殖和功能。雌激素以其刺激各种组织中细胞增殖的能力而闻名。然而，很少有人知道TCDD和雌二醇-17 β（E-2）之间的任何相互作用，影响肾近曲小管细胞增殖和Na+/葡萄糖共转运蛋白的活性。因此，TCDD和E-2对[H-3]-胸苷掺入和α-甲基-D-吡喃葡萄糖苷（α-MG）摄取的影响进行了研究，在原代兔肾近曲小管细胞（PTC）。TCDD（>10（-10）M，> 1h）抑制[H-3]-胸苷掺入和c-fos转录，而E-2（>10（-9）M，24 h）则刺激[H-3]-胸苷掺入和c-fos转录。芳烃受体（AhR）激动剂、β-萘啶酮（β-NF）和多氯联苯（PCBs）（10（-6）M）协同增强TCDD诱导的[H-3]-胸苷掺入抑制。然而，AhR拮抗剂，α-萘酮（α-NF）以及E2阻断TCDD诱导的抑制[H-3]-胸苷掺入。TCDD（10（-8）M，48 h）特异性抑制α-MG摄取，其作用是由于V-max值，而不是Kn值。事实上，TCDD降低Na+/葡萄糖协同转运蛋白1，2（SGLT 1，2）蛋白水平与对照组相比。此外，TCDD诱导的α-MG摄取抑制被α-NF或E-2阻断。总之，TCDD抑制[H-3]胸苷掺入和α-MG摄取，和E-2阻断TCDD的影响，在原代培养的肾近曲小管细胞。(C)2004爱思唯尔有限公司保留所有权利。
TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) is a highly toxic environmental toxicant that alters cell proliferation and function. Estrogens are noted for their ability to stimulate cell proliferation in various tissues. However, little is known about any interaction between TCDD and estradiol-17beta (E-2) that affects renal proximal tubule cell proliferation and Na+/glucose cotransporters' activity. Thus, the effects of TCDD and E-2 on [H-3]-thymidine incorporation and on alpha-methyl-D-glucopyranoside (alpha-MG) uptake were investigated in the primary rabbit kidney proximal tubule cells (PTCs). TCDD (>10(-10) M >1 h) inhibited [H-3]-thymidine incorporation and c-fos transcripts in real-time RT-PCR, whereas E-2 (>10(-9) M, 24 h) stimulated them. Aryl hydrocarbon receptor (AhR) agonists, beta-naphthoflavone (beta-NF) and polychlorinated biphenyls (PCBs) (10(-6) M) synergistically increased the TCDD-induced inhibition of [H-3]-thymidine incorporation. However, the AhR antagonist, alpha-naphthoflavone (alpha-NF) as well as E2 blocked TCDD-induced inhibition of [H-3]-thymidine incorporation. TCDD (10(-8) M, 48 h) specifically inhibited alpha-MG uptake and its effect was due to V-max value but not Kn, value. Indeed, TCDD decreased Na+/glucose cotransporter 1, 2 (SGLT1, 2) protein level compared with control. In addition, TCDD-induced inhibition of alpha-MG uptake was blocked by alpha-NF or E-2. In conclusion, TCDD inhibited [H-3]thymidine incorporation and alpha-MG uptake, and E-2 blocked TCDDs effects in primary cultured renal proximal tubule cells. (C) 2004 Elsevier Ltd. All rights reserved.