Age-dependent expression of hephaestin in the brain of ceruloplasmin-deficient mice.
Aceruloplasminemia is an autosomal recessive disorder caused by mutations in the ceruloplasmin (CP) gene. It is characterized by iron accumulation in the brain and in visceral organs. However, little is known about the mechanism of iron transport in these regions. Adult CP null (CP(-/-)) mice show increased iron deposition in several regions of brain, such as the cerebellum and brainstem. In this study, we investigated the expression of the ceruloplasmin homolog hephaestin (Heph) in the brain of CP(-/-) mice as a function of age. In the cerebral cortex and caudate putamen of 80-week-old CP(-/-) mice, the expression of Heph increased significantly whilst iron levels remain normal [Patel BN, Dunn RJ, Jeong SY, Zhu Q, Julien JP, David S. Ceruloplasmin regulates iron levels in the CNS and prevents free radical injury. J Neurosci 2002;22(15):6578-6], indicating that Heph might compensate for the loss of CP. In contrast, the substantia nigra and cerebellum of 80-week-old CP(-/-) mice accumulate iron but do not express high levels or significant decrease of Heph, suggesting that Heph does not replace CP in these regions. These data suggest that Heph may compensate for the loss of CP in a region-specific manner.
Cui
Rui
R
Laboratory of Molecular Iron Metabolism, College of Life Science, Hebei Normal University, Shijiazhuang 050016, Hebei Province, China.
Duan
Xiang-Lin
XL
Anderson
Gregory J
GJ
Qiao
Ya-Tiao
YT
Yu
Peng
P
Qian
Zhong-Ming
ZM
Yoshida
Kunihiro
K
Takeda
Shin'ichi
S
Guo
Pei
P
Yang
Zhen-Ling
ZL
Chang
Yan-Zhong
YZ
D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002570:Ceruloplasmin / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D004805:Ependyma / Q000378:metabolism / Q000473:pathology; D017353:Gene Deletion; D005838:Genotype; D007150:Immunohistochemistry; D019190:Iron Overload / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype
C117324:Heph protein, mouse; D008565:Membrane Proteins; D002570:Ceruloplasmin