Kelleher Shannon L, Lopez Veronica, Lönnerdal Bo, Dufner-Beattie Jodi, Andrews Glen K
Dept. of Nutritional Sciences, 222 Chandlee Laboratory, University Park, PA 16802-6110, USA.
Am J Physiol Regul Integr Comp Physiol. 2009 Jul;297(1):R194-201. doi: 10.1152/ajpregu.00162.2009. Epub 2009 May 20.
The lactating mammary gland is composed of multiple cell types that tightly coordinate the accumulation, production, and secretion of milk components, including essential metals such as zinc (Zn). Our previous studies in animal and cell models implicated the Zn transporter Zip3 (Slc39a3) in mammary gland Zn acquisition. Herein, we investigated this hypothesis directly by utilizing Zip3-null mice. Our data verify that Zip3 is expressed in secretory mammary cells; however, Zip3 does not play a major role in Zn import from the maternal circulation. Importantly, the primary localization of Zip3 was associated with the luminal membrane of the secretory mammary cells. Consistent with this localization, Zn transfer studies using (65)Zn revealed that Zn retention in the secreted milk pool and milk Zn concentration was higher in Zip3-null compared with wild-type mice. Although total mammary gland Zn concentration was not altered, Zip3-null mice also had altered mammary tissue architecture, increased number of apoptotic cells, and reduced mammary gland weight implicating subtle changes in Zip3-mediated intracellular Zn pools in apoptosis regulation. Taken together, our data indicate that Zip3 does not participate in the acquisition of Zn from maternal circulation for secretion into milk but, in contrast, primarily plays a role in the reuptake and cellular retention of Zn in the mammary gland from the previously secreted milk pool, thus regulating cellular function.
泌乳期乳腺由多种细胞类型组成，这些细胞紧密协调乳汁成分（包括锌（Zn）等必需金属）的积累、产生和分泌。我们之前在动物和细胞模型中的研究表明，锌转运蛋白Zip3（Slc39a3）参与乳腺对锌的摄取。在此，我们通过利用Zip3基因敲除小鼠直接研究了这一假设。我们的数据证实Zip3在分泌型乳腺细胞中表达；然而，Zip3在从母体循环中摄取锌方面并不起主要作用。重要的是，Zip3的主要定位与分泌型乳腺细胞的腔膜相关。与此定位一致，使用（65）Zn进行的锌转运研究表明，与野生型小鼠相比，Zip3基因敲除小鼠分泌的乳汁池中锌的保留量和乳汁锌浓度更高。虽然乳腺总锌浓度没有改变，但Zip3基因敲除小鼠的乳腺组织结构也发生了改变，凋亡细胞数量增加，乳腺重量减轻，这表明Zip3介导的细胞内锌池在细胞凋亡调节中发生了细微变化。综上所述，我们的数据表明，Zip3不参与从母体循环中摄取锌并分泌到乳汁中，相反，它主要在乳腺中从先前分泌的乳汁池中重新摄取和细胞保留锌方面发挥作用，从而调节细胞功能。
