Transferrin enhances the antiproliferative effect of aluminum on osteoblast-like cells.
Transferrin enhances the antiproliferative effect of aluminum on osteoblast-like cells.
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DOI：
10.1152/ajpendo.1991.260.4.e537
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发表时间：
1991-04
期刊：
影响因子：
--
通讯作者：
K. Kasai;M. Hori;W. Goodman
中科院分区：
文献类型：
--
作者：
K. Kasai;M. Hori;W. Goodman
铝（Al）在体内的滞留会导致代谢性骨病。这种疾病的特征是成骨细胞数量减少，这一特征表明骨细胞增殖或分化障碍。由于铝和铁（Fe）可与血浆中的转铁蛋白（TF）结合，因此在UMR-106-01成骨细胞样细胞中，通过测量在无血清培养基（SFM）中孵育48小时期间氚化胸苷（[3 H]-TdR）掺入DNA（计数min-1.微克细胞蛋白-1，平均值+/- SE）来检查TF作为成骨细胞增殖修饰剂的作用。在TF的情况下，DNA合成下降时，媒体水平的铝超过6-10 μ M。然而，在与铝部分饱和的TF（Al-TF）孵育期间，对生理水平的不饱和TF（apo-TF）的促有丝分裂反应减弱。当以部分饱和的Ga-TF形式加入SFM中时，在与抗增殖剂镓（Ga）孵育的细胞中观察到类似的抑制反应。TF在成骨细胞样细胞中对Al的抑制剂量-反应曲线中向左移动;因此，在含有部分饱和Al-TF的SFM中生长的细胞中，在Al的培养基浓度显著降低时，DNA合成减少。结果表明，TF是铝对成骨细胞样细胞DNA合成的抑制作用的一个重要决定因素，在微摩尔水平的铝，可以发生在血浆中在体内。
Aluminum (Al) retention in the body can cause metabolic bone disease. This disorder is characterized by reductions in the number of osteoblasts, a feature that suggests a disturbance in bone cell proliferation or differentiation. Because Al as well as iron (Fe) can bind to transferrin (TF) in plasma, the role of TF as a modifier of osteoblast proliferation was examined in UMR-106-01 osteoblast-like cells by measuring the incorporation of tritiated thymidine ([3H]-TdR) into DNA (counts.min-1.microgram cell protein-1, means +/- SE) during 48-h incubations in serum-free medium (SFM). In the absence of TF, DNA synthesis decreased when media levels of Al exceeded 6-10 microM. The mitogenic response to physiological levels of unsaturated TF (apo-TF) was attenuated however during incubations with TF that was partially saturated with Al (Al-TF). A similar inhibitory response was seen in cells incubated with the antiproliferative agent gallium (Ga) when added to SFM as partially saturated Ga-TF. TF produced a shift to the left in the inhibitory dose-response curve to Al in osteoblast-like cells; thus, DNA synthesis decreased at substantially lower media concentrations of Al in cells grown in SFM containing partially saturated Al-TF. The results indicate that TF is an important determinant of the inhibitory effect of Al on DNA synthesis by osteoblast-like cells at the micromolar levels of Al that can occur in plasma in vivo.