Lin F J, Fitzpatrick J W, Iannotti C A, Martin D S, Mariani B D, Tuan R S
Department of Orthopedic Surgery, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Placenta. 1997 May;18(4):341-56. doi: 10.1016/s0143-4004(97)80069-0.
Maternal exposure to cadmium (Cd) during pregnancy has been linked to low fetal birthweight, which may be attributed to placental damage and/or dysfunction in nutrient transport. Previous studies have suggested that Cd is accumulated in the placenta, and that placental transport of calcium (Ca) and zinc (Zn) is perturbed by Cd. To investigate the mechanism of Cd perturbation of Ca transport, we used JEG-3, a human choriocarcinoma cell line which exhibits trophoblastic properties, to analyse Cd effects in vitro. Treatment with Cd at low, physiologically relevant concentrations (e.g. 0.04 microM) did not result in obvious changes in cell morphology or integrity, whereas higher concentrations (> or = 0.16 microM) affected cell integrity. With lower concentrations of Cd treatment for 24 h, activities of cellular Ca uptake and transport, and Ca2+ binding were decreased, and intracellular [Ca2+] ([Ca2+]i) profile was also altered; however, membrane-associated Ca(2+)-activated ATPase activity remained relatively unchanged. Interestingly, cellular Ca uptake activity was unaffected by short-term (30 min) Cd pretreatment. The 24-h Cd treatment also resulted in elevated expression of the metal-binding protein, metallothionein, whereas the expression of a trophoblast-specific cytosolic Ca(2+)-binding protein (HCaBP) was drastically reduced. These results strongly suggest that Cd exposure significantly compromises the Ca handling ability of trophoblastic cells; this effect is probably not due to perturbations in Ca channel or membrane Ca pump activities, but rather a consequence of alterations in subcellular, cytosolic Ca2+ binding activities.
孕期母体接触镉（Cd）与低出生体重儿有关，这可能归因于胎盘损伤和/或营养物质转运功能障碍。先前的研究表明，Cd在胎盘中蓄积，且Cd会干扰胎盘对钙（Ca）和锌（Zn）的转运。为了研究Cd干扰Ca转运的机制，我们使用具有滋养层细胞特性的人绒毛膜癌细胞系JEG-3进行体外Cd效应分析。用生理相关的低浓度Cd（例如0.04微摩尔）处理不会导致细胞形态或完整性出现明显变化，而较高浓度（≥0.16微摩尔）则会影响细胞完整性。用较低浓度的Cd处理24小时后，细胞Ca摄取和转运活性以及Ca2+结合活性降低，细胞内[Ca2+]（[Ca2+]i）分布也发生改变；然而，膜相关的Ca(2+)激活ATP酶活性相对保持不变。有趣的是，短期（30分钟）Cd预处理不影响细胞Ca摄取活性。24小时的Cd处理还导致金属结合蛋白金属硫蛋白的表达升高，而滋养层特异性胞质Ca(2+)结合蛋白（HCaBP）的表达则大幅降低。这些结果有力地表明，接触Cd会显著损害滋养层细胞的Ca处理能力；这种效应可能不是由于Ca通道或膜Ca泵活性受到干扰，而是亚细胞、胞质Ca2+结合活性改变的结果。
