Journal
CELL BIOCHEMISTRY AND BIOPHYSICS
Volume 80, Issue 2, Pages 385-393Publisher
HUMANA PRESS INC
DOI: 10.1007/s12013-022-01061-9
Keywords
Ceruloplasmin; Iron metabolism; Brain; Iron metabolism-related protein
Funding
- Key R&D Program of Hebei Province [18277752D]
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Iron accumulation is an important cause of brain diseases. Ceruloplasmin (Cp) plays a key role in iron homeostasis and its deficiency leads to iron accumulation in various tissues and organs. Although there is no obvious change in iron content in brain tissues, Cp deficiency affects the expression of iron metabolism-related proteins in the midbrain. Furthermore, Cp deficiency impairs the behavioral ability of mice.
Iron accumulation is an important cause of various brain diseases. As a ferroxidase, ceruloplasmin (Cp) plays a key role in iron homeostasis and its abnormal activity leads to iron accumulation. However, the detailed biological function of Cp in brain iron homeostasis needs to be investigated. In this study, Cp knockout mice were prepared and the changes in iron content and protein expression related to iron metabolism were detected. The results showed that iron accumulation occurred in multiple tissues and organs of Cp knockout mice, but there was no obvious change in brain tissues. However, Cp deficiency affected the expression of many iron metabolism-related proteins in midbrain, such as DMT1+IRE, heavy chain ferritin (H-ferritin) and light chain ferritin (L-ferritin). Cp deficiency also impaired the behavioral ability of mice, including weakened exercise ability and reduced motor coordination. In vitro cell experiment indicated that the sensitivity of Cp knockout neuron and astrocyte to hypoxia was higher than that of wild type, which means Cp deficiency leads to the damage of cell self-protection. All these results confirm that Cp exerts a protective effect on the brain by regulating iron metabolism.
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