Ohrvik Helena, Tydén Eva, Artursson Per, Oskarsson Agneta, Tallkvist Jonas
Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Box 7028, 75007 Uppsala, Sweden.
ISRN Toxicol. 2013 Jan 27;2013:892364. doi: 10.1155/2013/892364. Print 2013.
Newborns have a higher gastrointestinal uptake of cadmium than adults. In adults, the iron transporters DMT1 and FPN1 are involved in the intestinal absorption of cadmium, while in neonates, the mechanisms for cadmium absorption are unknown. We have investigated possible cadmium transporters in the neonatal intestine by applying a model of immature human intestinal epithelial Caco-2 cells. To mimic the continuous cadmium exposure via diet in neonates, cells were allowed to differentiate for 7 days in medium containing 1 μ M CdCl2. A dramatic upregulation of the MT1 gene expression followed cadmium pretreatment, indicating a high sensitivity of the immature cells to cadmium. Cadmium pretreatment increased the basolateral efflux of (109)Cd, without causing any effects on the passive diffusion of mannitol or the transepithelial electrical resistance. The augmented transport of cadmium was correlated to an upregulation of MRP1 gene expression and increased activity of the efflux protein MRP1. No effects were observed on gene expression of the efflux proteins MRP2 and P-gp or the iron transporters DMT1, DMT1-IRE and FPN1. In conclusion, our data indicate that continuous cadmium exposure increases the absorption of the metal in immature intestinal cells and that MRP1 is involved in the intestinal cadmium absorption in newborns.
新生儿对镉的胃肠道吸收高于成年人。在成年人中，铁转运蛋白DMT1和FPN1参与肠道对镉的吸收，而在新生儿中，镉吸收的机制尚不清楚。我们通过应用未成熟的人肠上皮Caco-2细胞模型，研究了新生儿肠道中可能的镉转运蛋白。为模拟新生儿通过饮食持续接触镉的情况，使细胞在含有1μM CdCl2的培养基中分化7天。镉预处理后MT1基因表达显著上调，表明未成熟细胞对镉高度敏感。镉预处理增加了(109)Cd的基底外侧流出，而对甘露醇的被动扩散或跨上皮电阻没有任何影响。镉转运增加与MRP1基因表达上调和流出蛋白MRP1活性增加相关。未观察到对流出蛋白MRP2和P-gp或铁转运蛋白DMT1、DMT1-IRE和FPN1基因表达的影响。总之，我们的数据表明，持续接触镉会增加未成熟肠道细胞对金属的吸收，并且MRP1参与新生儿肠道对镉的吸收。
