title: Serum ceruloplasmin protein expression and activity increases in iron-deficient rats and is further enhanced by higher dietary copper intake.
abstract: Increases in serum and liver copper content are noted during iron deficiency in mammals, suggesting that copper-dependent processes participate during iron deprivation. One point of intersection between the 2 metals is the liver-derived, multicopper ferroxidase ceruloplasmin (Cp) that is important for iron release from certain tissues. The current study sought to explore Cp expression and activity during physiologic states in which hepatic copper loading occurs (eg, iron deficiency). Weanling rats were fed control or low iron diets containing low, normal, or high copper for ∼ 5 weeks, and parameters of iron homeostasis were measured. Liver copper increased in control and iron-deficient rats fed extra copper. Hepatic Cp mRNA levels did not change; however, serum Cp protein was higher during iron deprivation and with higher copper consumption. In-gel and spectrophotometric ferroxidase and amine oxidase assays demonstrated that Cp activity was enhanced when hepatic copper loading occurred. Interestingly, liver copper levels strongly correlated with Cp protein expression and activity. These observations support the possibility that liver copper loading increases metallation of the Cp protein, leading to increased production of the holo enzyme. Moreover, this phenomenon may play an important role in the compensatory response to maintain iron homeostasis during iron deficiency.
authors.affiliation: Department of Food Science & Human Nutrition, University of Florida, Gainesville, FL, USA.
authors.forename: Perungavur N
authors.initials: PN
authors.lastname: Ranganathan
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.forename: Lingli
authors.initials: L
authors.lastname: Jiang
authors.forename: Changae
authors.initials: C
authors.lastname: Kim
authors.forename: James F
authors.initials: JF
authors.lastname: Collins
mesh_terms: D000818:Animals; D001774:Blood Chemical Analysis; D002570:Ceruloplasmin / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D003300:Copper / Q000032:analysis / Q000097:blood / Q000494:pharmacology*; D004032:Diet; D004435:Eating / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D007501:Iron / Q000032:analysis / Q000097:blood; D000090463:Iron Deficiencies; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044967:Serum / Q000201:enzymology / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D003300:Copper; D007501:Iron; D002570:Ceruloplasmin