Laboratory of Molecular Iron Metabolism, The Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Sciences, Hebei Normal University, Shijiazhuang 050024, China.
Laboratory of Molecular Iron Metabolism, The Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Sciences, Hebei Normal University, Shijiazhuang 050024, China.
Life Sci. 2020 Aug 15;255:117838. doi: 10.1016/j.lfs.2020.117838. Epub 2020 May 22.
Dysregulation of iron homeostasis in the body causes a variety of diseases. Iron deficiency leads to anemia, whereas iron overload aggravates cellular oxidative stress. Nuclear factor erythroid-2-related factor 2 (Nrf2) is a protein that is activated in the nucleus and turns on the production of antioxidant enzymes, protecting cell against oxidative damage. This study aimed to investigate whether Nrf2 gene knockout influences iron homeostasis in aging mice.
Iron content and iron metabolism-related proteins were assessed in different organs and blood serum of the 18 month-old Nrf2 knockout (Nrf2) mice in comparison with the wild-type (WT) mice.
Results showed that the iron contents in spleen and liver all increased, and expression levels of iron transporters were altered in Nrf2 mice. In particularly, we found that the expression of iron export protein ferroportin 1 (Fpn1) in liver, spleen and small intestine all decreased in Nrf2 mice, which might account for the deposition of iron in different organs and the increased ROS. Surprisingly, we found that the serum iron level of Nrf2 mice did not decrease, but increased significantly even when the iron absorption at small intestine decreased. Our further investigation revealed that the increase of serum iron was due to the release of iron from the hemolysis of erythrocytes, which caused by the increased ROS level in red blood cells of the Nrf2 mice.
These findings provide a more comprehensive understanding of the important role of Nrf2 in the regulation of systemic iron metabolism.
体内铁稳态失调会导致多种疾病。缺铁会导致贫血，而铁过载会加重细胞氧化应激。核因子红细胞 2 相关因子 2（Nrf2）是一种在细胞核中被激活的蛋白质，它可以开启抗氧化酶的产生，保护细胞免受氧化损伤。本研究旨在探讨 Nrf2 基因敲除是否会影响衰老小鼠的铁稳态。
我们评估了 18 月龄 Nrf2 敲除（Nrf2）小鼠与野生型（WT）小鼠不同器官和血清中的铁含量和铁代谢相关蛋白。
结果表明，Nrf2 小鼠的脾脏和肝脏铁含量均增加，铁转运蛋白的表达水平发生改变。特别是，我们发现 Nrf2 小鼠肝脏、脾脏和小肠中铁输出蛋白 Ferroportin 1（Fpn1）的表达均降低，这可能是导致不同器官铁沉积和 ROS 增加的原因。令人惊讶的是，我们发现 Nrf2 小鼠的血清铁水平并没有降低，反而显著增加，即使小肠的铁吸收减少。我们进一步的研究表明，血清铁的增加是由于 Nrf2 小鼠红细胞中的 ROS 水平增加导致红细胞溶血，从而释放铁。
这些发现提供了对 Nrf2 在调节全身铁代谢中的重要作用的更全面的理解。
