Zhenzhen Liu1, Kang Han1, Xuege Huo1, Bingqi Yan1, Mohan Gao1, Xin Lv1, Peng Yu1, Guofen Gao2, Yan-Zhong Chang3. 1. 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. 2. 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. Electronic address: guofen83@hotmail.com. 3. 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. Electronic address: frankyzchang@yahoo.com.hk.
Abstract
AIMS: 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. MATERIALS AND METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: These findings provide a more comprehensive understanding of the important role of Nrf2 in the regulation of systemic iron metabolism.
AIMS: 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. MATERIALS AND METHODS: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. KEY FINDINGS: 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. SIGNIFICANCE: These findings provide a more comprehensive understanding of the important role of Nrf2 in the regulation of systemic iron metabolism.
Authors: Tony Heurtaux; David S Bouvier; Alexandre Benani; Sergio Helgueta Romero; Katrin B M Frauenknecht; Michel Mittelbronn; Lasse Sinkkonen Journal: Antioxidants (Basel) Date: 2022-07-22