title: Age-dependent expression of hephaestin in the brain of ceruloplasmin-deficient mice.
abstract: 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.
authors.affiliation: Laboratory of Molecular Iron Metabolism, College of Life Science, Hebei Normal University, Shijiazhuang 050016, Hebei Province, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Cui
authors.forename: Xiang-Lin
authors.initials: XL
authors.lastname: Duan
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Anderson
authors.forename: Ya-Tiao
authors.initials: YT
authors.lastname: Qiao
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
authors.forename: Zhong-Ming
authors.initials: ZM
authors.lastname: Qian
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Yoshida
authors.forename: Shin'ichi
authors.initials: S
authors.lastname: Takeda
authors.forename: Pei
authors.initials: P
authors.lastname: Guo
authors.forename: Zhen-Ling
authors.initials: ZL
authors.lastname: Yang
authors.forename: Yan-Zhong
authors.initials: YZ
authors.lastname: Chang
mesh_terms: 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
chemical_list: C117324:Heph protein, mouse; D008565:Membrane Proteins; D002570:Ceruloplasmin