Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
Toxicology. 2013 Jan 7;303:99-106. doi: 10.1016/j.tox.2012.10.023. Epub 2012 Nov 8.
Octylphenol (OP) is the degradative product of alkylphenol ethoxylates that are widely used to produce rubber, pesticides, and paints. Bisphenol A (BPA) is an organic compound with two functional phenol groups, and used for manufacturing polycarbonate plastic and epoxy resins, as well as other applications. OP and BPA are known as endocrine disruptors (EDs) with estrogenic activities, and may disturb natural calcium (Ca) metabolism. In the present study, the effects of OP and BPA on Ca levels in the serum and expression of Ca transport genes in the duodenum, and kidney were investigated in pregnant mice. Calbindin refers to several Ca-binding proteins originally described as vitamin D-dependent Ca-binding factors in the intestine, and kidney of birds and mammals. Transient receptor potential cation channel, subfamily V, member 6 (TRPV6) and transient receptor potential cation channel, subfamily V, member 5 (TRPV5) are Ca entry channels responsible for Ca absorption in the kidney and intestine, respectively. From 6.5 to 16.5 day post coitus (dpc), pregnant mice were given oral doses of 17α-ethynylestradiol (EE, 0.2mg/kg/day), BPA (5 or 50mg/kg/day), or OP (3, 12, or 48 mg/kg/day) dissolved in corn oil. Samples of the duodenum, kidney, and blood were obtained from the mice on day 17.5 of pregnancy. Serum Ca levels were decreased in the groups treated with OP and BPA. The expression levels of Ca transport genes, TRPV5 and calbindin-D9k (CaBP-9k), in the kidney were decreased after treatment with OP and BPA. Duodenal expression of TRPV6 was also reduced by BPA and OP administration. CaBP-9k expression was differentially regulated by BPA and OP. Transcriptional and translational levels of CaBP-9k were decreased by EE and BPA but increased by a high dose of OP. Taken together, our findings demonstrate that OP and BPA regulated the expression of genes associated with Ca transport in the pregnant mice, which may result in the decreased serum Ca levels.
辛基酚 (OP) 是烷基酚聚氧乙烯醚的降解产物,被广泛用于制造橡胶、农药和油漆。双酚 A (BPA) 是一种具有两个官能团酚的有机化合物,用于制造聚碳酸酯塑料和环氧树脂以及其他应用。OP 和 BPA 被称为具有雌激素活性的内分泌干扰物 (EDs),可能会干扰天然钙 (Ca) 代谢。在本研究中,研究了 OP 和 BPA 对怀孕小鼠血清中 Ca 水平以及十二指肠和肾脏中 Ca 转运基因表达的影响。钙结合蛋白最初被描述为鸟类和哺乳动物肠道和肾脏中维生素 D 依赖性 Ca 结合因子,属于几种 Ca 结合蛋白。瞬时受体电位阳离子通道,亚家族 V,成员 6 (TRPV6) 和瞬时受体电位阳离子通道,亚家族 V,成员 5 (TRPV5) 是负责肾脏和肠道中 Ca 吸收的 Ca 进入通道。从交配后 6.5 至 16.5 天 (dpc),给怀孕小鼠口服给予 17α-乙炔雌二醇 (EE,0.2mg/kg/天)、BPA (5 或 50mg/kg/天) 或 OP (3、12 或 48mg/kg/天) 溶于玉米油。在怀孕第 17.5 天从小鼠中获得十二指肠、肾脏和血液样本。OP 和 BPA 处理组的血清 Ca 水平降低。OP 和 BPA 处理后,肾脏中 Ca 转运基因 TRPV5 和钙结合蛋白-D9k (CaBP-9k) 的表达水平降低。BPA 和 OP 给药也降低了十二指肠 TRPV6 的表达。BPA 和 OP 对 CaBP-9k 的表达进行了不同的调节。EE 和 BPA 降低了 CaBP-9k 的转录和翻译水平,但高剂量的 OP 增加了 CaBP-9k 的表达。总之,我们的研究结果表明,OP 和 BPA 调节了怀孕小鼠中与 Ca 转运相关的基因表达,这可能导致血清 Ca 水平降低。