Plasma peptidylglycine alpha-amidating monooxygenase (PAM) and ceruloplasmin are affected by age and copper status in rats and mice

2007

Biometals

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Copper deficiency lowers brain copper and iron during development. The reduced iron content could be due to hypoferremia. Experiments were conducted to evaluate plasma iron and "ferroxidase" hypotheses by determining copper and iron status of Holtzman albino rats following gestational/ lactational copper deficiency. Copper deficient (Cu−) dams on treatment for 5 weeks, two of gestation and three of lactation, had markedly lower copper content of milk and mammary tissue, and lower milk iron. Newborn pups from Cu− dams had lower copper and iron concentrations. Compared to Cu+ pups, Cu− pups, analyzed between postnatal age (P) 0 and P26, were smaller, anemic, had lower plasma iron, cardiac hypertrophy, and near zero ceruloplasmin activity. Liver copper in Cu+ pups increased then decreased during development and major reductions were evident in Cu− pups. Liver iron in Cu+ pups decreased with age while nursing but increased after eating solid food. Liver iron was lower in Cu− pups at P0 and P13 and normal at P20 and P26. Small intestinal copper decreased with age in Cu+ pups and was lower in Cu− pups. Intestinal iron levels in Cu-pups were higher than Cu+ pups postweaning in some experiments. Reduction in plasma iron in Cu− pups is likely due to a decreased "ferroxidase" function leading to lower placental iron transport, a lower milk iron diet, and partial block in iron uptake from intestine but is not due to failure to mobilize hepatic iron, in contrast to older rats eating diet with adequate iron.

Section: Discussionsupporting

confidence: 57%

Multiple mechanisms account for lower plasma iron in young copper deficient rats

2007

Biometals

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“…Although, in the current studies restriction of copper in mice began only shortly before birth, prior studies with full gestational copper deprivation also failed to show a reduction in brain iron in suckling mouse pups despite severe copper deficiency (Prohaska, 1983). Furthermore, previous comparisons of Cu-rat and mouse dams showed that mouse dams were equally, if not more, copper deficient compared to rats following the same nutritional protocols used in the current studies (Prohaska and Broderius, 2006).…”

Section: Discussionmentioning

confidence: 54%

“…Thus, it is possible that Cu-suckling mammals are iron deficient (Pyatskowit and Prohaska, 2008). Supportive evidence of this idea was the observation that liver iron is lower in Cu-rodents at P3 (Prohaska and Broderius, 2006). Others have also recently shown that fetal liver iron is lower in Cu-rat pups (Andersen et al, 2007).…”

Section: Discussionmentioning

confidence: 93%

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Copper deficient rats and mice both develop anemia but only rats have lower plasma and brain iron levels

Comparative Biochemistry and Physiology Part C: Toxicology &

2008

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Iron homeostasis depends on adequate dietary copper but the mechanisms are unknown. Mice (Mus musculus) and rat (Rattus norvegicus) offspring were compared to determine the effect of dietary copper deficiency (Cu-) on iron status of plasma, liver, brain and intestine. Holtzman rat and Hsd:ICR (CD-1) outbred albino mouse dams were fed a Cu-diet and drank deionized water or Cu supplemented water. Offspring were sampled at time points between postnatal ages 13 and 32. Curat and mouse pups were both anemic, but only rat pups had lower plasma and brain iron levels. Plasma iron was lower throughout the suckling period in Cu-rats but not Cu-mice. Cu-mice derived from dams restricted of Cu only during lactation were also severely anemic without hypoferremia. Intestinal metal analysis confirmed that Cu-pups had major reductions in intestinal concentration of Cu, increased Fe, and normal Zn. However, whole mouse (less the intestine) analysis demonstrated normal content of Fe indicating that the limitation in iron transport by intestinal hephaestin had no consequence to total iron reserves of the mouse. Further research will be needed to determine the reason Cu-mice were anemic since the "ferroxidase" hypothesis does not explain this phenotype.

“…Copper (Cu) is one of these micronutrients that is essential for all biological systems and serves as a cofactor for many mammalian enzymes (Prohaska, 2006). Ewes grazing on pastures low in Cu delivered lambs suffering from neonatal ataxia (Bennetts and Chapman, 1937).…”

Section: Introductionmentioning

confidence: 99%

Rodent brain and heart catecholamine levels are altered by different models of copper deficiency

Comparative Biochemistry and Physiology Part C: Toxicology &

2007

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Limiting dopamine β-monooxygenase results in lower norepinephrine (NE) and higher dopamine (DA) concentrations in copper-deficient (Cu−) tissues compared to copper-adequate (Cu+) tissues. Mice and rat offspring were compared to determine the effect of differences in dietary copper (Cu) deficiency started during gestation or lactation on catecholamine, NE and DA, content in brain and heart. Holtzman rat and Hsd:ICR (CD-1) outbred albino mouse dams were fed a Cu-diet and drank deionized water or Cu supplemented water. Offspring were sampled at time points between postnatal ages 12 and 27. For both rat and mouse Cu-tissue, NE and DA changes were greater at later ages. Though Cu restriction began earlier in rats than mice in the gestational model, brain NE reduction was more severe in Cu-mice than Cu-rats. Cardiac NE reduction was similar in Cu-rodents in the gestation models. In the lactation model, mouse catecholamines were altered more than rat catecholamines. Furthermore, following lactational Cu deficiency Cu-mice were anemic and exhibited cardiac hypertrophy, Cu-rats displayed neither phenotype. Within a species, changes were more severe and proportional to the length of Cu deprivation. Lactational Cu deficiency in mice had greater consequences than in rats.