Thompson Khristy, Molina Ramon M, Donaghey Thomas, Brain Joseph D, Wessling-Resnick Marianne
Department of Genetics and Complex Diseases, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
Am J Physiol Gastrointest Liver Physiol. 2007 Sep;293(3):G640-4. doi: 10.1152/ajpgi.00153.2007. Epub 2007 Jul 19.
Divalent metal transporter-1 (DMT1) mediates dietary nonheme iron absorption. Belgrade (b) rats have defective iron metabolism due to a mutation in the DMT1 gene. To examine the role of DMT1 in neonatal iron assimilation, b/b and b/+ pups were cross-fostered to F344 Fischer dams injected with (59)FeCl(3) twice weekly during lactation. Tissue distribution of the radioisotope in the pups was determined at weaning (day 21). The b/b pups had blood (59)Fe levels significantly lower than b/+ controls but significantly higher (59)Fe tissue levels in heart, bone marrow, skeletal muscle, kidney, liver, spleen, stomach, and intestines. To study the pharmacokinetics of nonheme iron absorption at the time of weaning, (59)FeCl(3) was administered to 21-day-old b/b and b/+ rats by intragastric gavage. Blood (59)Fe levels measured 5 min to 4 h postgavage were significantly lower in b/b rats, consistent with impaired DMT1 function in intestinal iron absorption. Tissue (59)Fe levels were also lower in b/b rats postgavage. Combined, these data suggest that DMT1 function is not essential for iron assimilation from milk during early development in the rat.
二价金属转运蛋白1(DMT1)介导膳食非血红素铁的吸收。贝尔格莱德(b)大鼠由于DMT1基因突变而存在铁代谢缺陷。为了研究DMT1在新生儿铁同化中的作用,将b/b和b/+幼崽交叉寄养给在哺乳期每周两次注射(59)FeCl(3)的F344 Fischer母鼠。在断奶时(第21天)测定幼崽体内放射性同位素的组织分布。b/b幼崽的血液(59)Fe水平显著低于b/+对照组,但在心脏、骨髓、骨骼肌、肾脏、肝脏、脾脏、胃和肠道中的(59)Fe组织水平显著更高。为了研究断奶时非血红素铁吸收的药代动力学,通过胃内灌胃给21日龄的b/b和b/+大鼠施用(59)FeCl(3)。灌胃后5分钟至4小时测得的b/b大鼠血液(59)Fe水平显著较低,这与肠道铁吸收中DMT1功能受损一致。灌胃后b/b大鼠的组织(59)Fe水平也较低。综合这些数据表明,在大鼠早期发育过程中,DMT1功能对于从乳汁中吸收铁并非必不可少。