金属转运蛋白ZIP14和ZnT10在维持锰(Mn)稳态中起着关键的生理作用。然而,Mn对这两种转运蛋白的体内调节尚不清楚。这里,我们研究了饮食中的锰摄入量如何通过给小鼠喂食低锰饮食来调节ZIP14和ZnT10,控制饮食,或高锰饮食6周。电感耦合等离子体质谱法用于测量Mn和铁(Fe)水平。通过蛋白质印迹分析测量ZIP14和ZnT10蛋白水平。虽然高锰饮食的小鼠血液中锰含量明显较高,肝脏,和大脑,低锰饮食组没有显示出匹配的减少,表明高锰摄入更有效地破坏小鼠的锰稳态。此外,铁的含量只有轻微的改变,表明Mn和Fe的独立运输机制。在高锰饮食组中,ZIP14和ZnT10在肝脏中都上调,以及在小肠中,表明这些转运蛋白在锰排泄中的协调作用。出乎意料的是,这种上调只发生在雄性小鼠身上,除肝脏ZIP14外,为广泛观察到的Mn稳态性别差异背后的机制提供了新的见解。
The metal transporters ZIP14 and
ZnT10 play key physiological roles in maintaining manganese (Mn) homeostasis. However, in vivo regulation of these two transporters by Mn is not understood. Here, we examined how dietary Mn intake regulates ZIP14 and
ZnT10 by feeding mice a low-Mn diet, a control diet, or a high-Mn diet for 6 weeks. Inductively coupled plasma mass spectrometry was used to measure Mn and iron (Fe) levels. ZIP14 and
ZnT10 protein levels were measured by western blot analysis. While mice on the high-Mn diet exhibited significantly higher levels of Mn in the blood, liver, and brain, the low-Mn diet group did not display matching reductions, indicating that high Mn intake is more effective in disrupting Mn homeostasis in mice. Additionally, Fe levels were only slightly altered, suggesting independent transport mechanisms for Mn and Fe. In the high-Mn diet group, ZIP14 and
ZnT10 were both upregulated in the liver, as well as in the small intestine, indicating a coordinated role for these transporters in Mn excretion. Unexpectedly, this upregulation only occurred in male mice, with the exception of hepatic ZIP14, providing new insight into mechanisms behind widely observed sex differences in Mn homeostasis.