Mechanism of sex difference in rat tissue iron stores

Linder, Maria C.; Moor, Joan R.; Scott, Laura E.; Munro, Hamish N.

doi:10.1016/0304-4165(73)90050-0

Cited by 41 publications

(15 citation statements)

References 13 publications

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“…These results are in keeping with previous data on iron storage in rats [5,10]. The serum ferritin concentration was found to differ significantly between female and male rats.…”

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Iron Content of Rat Serum Ferritin.

et al. 2001

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ABSTRACT. The serum ferritin concentration was significantly higher in female than in male rats, reflecting higher iron stores in females than in males. The mean iron/protein ratio of serum ferritin was 0.018 ± 0.008 (SD) (µg of Fe/µg of protein) in female rats and 0.011 ± 0.011 in male rats, being much lower than that of liver ferritin (0.233 ± 0.014 in females and 0.227 ± 0.020 in males). Iron loading of rats significantly increased serum ferritin concentration, but did not influence the iron content of serum ferritin. These results indicate that rat serum ferritin contains only a small amount of iron independent of body iron stores. KEY WORDS: ferritin iron, rat, serum ferritin.J. Vet. Med. Sci. 63(5): 587-589, 2001 Ferritin is a major iron-storage protein that is composed of 24 subunits of two types, termed H and L, the molecular masses of which are 21 kDa and 20 kDa, respectively [4,8,16]. Ferritin is present not only in cells but also in sera, and the serum ferritin level is positively correlated with body iron stores [1-3, 12, 15, 18]. The major function of tissue ferritin is to detoxify and store intracellular iron [8], and it contains a large amount of iron [5,14,17]. Serum ferritin has been found to have different amounts of iron in some mammals [6,9,13,20,22]. The physiological significance of serum ferritin and its iron remains unclear. Although rat serum ferritin was purified by Halliday et al. [7], its iron has yet to be determined. In the present study, the iron content of rat serum ferritin was measured, and compared with that of serum ferritin from other mammals.Female and male Wistar rats aged 9-12 weeks (Clea Japan, Tokyo, Japan) were used. Male rats were iron-loaded by intraperitoneal injection of iron dextran (100 mg iron/ml; Sigma, St. Louis, MO, U.S.A.) to increase body iron stores. Rats received single doses of 7 mg of iron three times on alternate days. Control rats were injected with an equivalent volume of 0.9% NaCl. Blood samples and livers were collected 2 days after the final administration from the untreated and iron-loaded rats under pentobarbital-induced anesthesia prior to sacrifice. The serum samples and tissues were stored at -25°C until use.Ferritin was purified from rat livers as previously described [19]. Protein was determined according to the method of Lowry et al.[11] using bovine serum albumin as a protein standard. Rabbit antisera to rat liver ferritin were prepared, and antibodies to the ferritin were purified from the antisera by affinity chromatography as described previously [19].Each rat liver was homogenized in a Waring blender for 3 min with 10 volumes of 10 mM Tris containing 0.2 mM Pefabloc SC (Merck, Darmstadt, Germany) as a serine proteinase inhibitor. Each homogenate was divided into two parts; one was used for measuring non-heme iron; and the other was centrifuged at 24,000 × g for 20 min at 4°C, then the supernatant (liver extract) was used for measuring ferritin protein and ferritin iron. Total non-heme iron in liver homogenates was measured as previo...

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“…These results are in keeping with previous data on iron storage in rats [5,10]. The serum ferritin concentration was found to differ significantly between female and male rats.…”

supporting

confidence: 82%

“…*: Significantly different from controls (P<0.01). The iron/protein ratio of liver ferritin was about 0.23 in female and male rats, essentially agreeing with previous data [5,10]. In the present study, the iron content of serum ferritin was found to be much lower than that of tissue ferritin.…”

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confidence: 82%

Iron Content of Rat Serum Ferritin.

et al. 2001

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“…Both male and female rats responded similarly to the same stimuli, although the baseline iron levels of males and females differ (being higher in females) as previously described. 26,27 To induce iron deficiency, animals were maintained on a semi-synthetic irondeficient diet (3 mg/kg wet weight) for 6 weeks before the investigations, as previously described.…”

Section: Animals Diets Treatments and Tissue Collectionmentioning

confidence: 99%

Severe iron deficiency blunts the response of the iron regulatory gene Hamp and pro-inflammatory cytokines to lipopolysaccharide

Darshan¹,

Frazer²,

Wilkins³

et al. 2010

Haematologica

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BackgroundExpression of the key iron regulatory hormone hepcidin is increased by some stimuli (iron loading, inflammation) but decreased by others (increased erythropoiesis, iron deficiency). We investigated the response of hepcidin to increased erythropoiesis and iron deficiency in the presence of an acute inflammation to assess the relative strengths of these stimuli. Design and MethodsSprague-Dawley rats were maintained on control or iron-deficient diets and treated with lipopolysaccharide to induce inflammation or phenylhydrazine to stimulate erythropoiesis. The levels of Hamp, IL-6 and a2m mRNA were determined by qualitative real-time polymerase chain reaction and those of serum interleukin-6 and tumor necrosis factor-a were measured by enzyme-linked immunosorbent assay. Cultured RAW264.7 and HuH7 cells were used in associated studies. ResultsThe increase in hepatic hepcidin levels induced by lipopolysaccharide was not affected by phenylhydrazine treatment but was blunted by iron deficiency. Lipopolysaccharide-treated iron-deficient animals also showed lower liver a2m mRNA and reduced serum interleukin-6 and tumor necrosis factor-a, suggesting a more generalized effect of iron deficiency. Similarly, RAW 264.7 cells treated with iron chelators and then stimulated with lipopolysaccharide showed lower IL-6 mRNA than cells treated with lipopolysaccharide alone. Huh7 cells treated with an iron chelator showed a blunted hepcidin response to interleukin-6, suggesting that the response of hepatic parenchymal cells to inflammatory cytokines may also be iron-dependent. ConclusionsIn any one physiological situation, net hepcidin levels are determined by the relative strengths of competing stimuli. The ability of severe iron deficiency to blunt the response to lipopolysaccharide of both hepcidin and other markers of inflammation suggests that adequate iron levels are necessary for a full acute phase response.Key words: hepcidin, a2m, erythropoiesis, iron, inflammation. Hamp and pro-inflammatory cytokines to lipopolysaccharide. Haematologica 2010;95(10):1660-1667. doi:10.3324/haematol.2010 This is an open-access paper. Citation: Darshan D, Frazer DM, Wilkins SJ, and Anderson GJ. Severe iron deficiency blunts the response of the iron regulatory gene Severe iron deficiency blunts the response of the iron regulatory gene

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“…tissue (4) and the role of liver xanthine dehydrogenase in the liberation of iron from liver ferritin stores (5). Wistar (WT) rats, meanwhile, have been used in iron-deficient anemic models (6,7).…”

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Differences in the Effect of Iron-Deficient Diet on Tissue Weight, Hemoglobin Concentration and Serum Triglycerides in Fischer-344, Sprague-Dawley and Wistar Rats.

Kasaoka

Yamagishi

Kitano

1999

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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SummaryThis study was designed to examine the diferences in the effect of an iron-deficient diet on iron metabolism in Fischer-344 (FC), Sprague-Dawley (SD) and Wistar (WT) rats based on hemoglobin (Hb), hematocrit (Hct), serum iron levels, growth rate and organ weight. Hb concentration was higher in FC rats (14mg/100mL) on the initial day than in SD (10) and WT (10) rats. Although the Hb level was significantly decreased in FC rats fed an iron-deficient (ID, 8mg/kg) diet for 33d compared to the FC rats fed an iron-adequate (IA, 50mg/kg) diet, the relative concentration of Hb was high in FC rats fed the ID diet as compared to the SD and WT rats fed the same diet. A similar relationship was detected between Hct and serum iron concentrations. Although serum triglycerides (TG) were significantly increased in each rat strain fed the ID diet as compared to the IA diet, the percentage of the value for the IA diet was lowest in FC rats (119%) fed the ID diet as compared to the SD (328) and WT (394) rats fed the same diet. Retroperitoneal fat pad was decreased in FC, SD and WT rats fed the ID diet as compared to the IA diet. SD rats were particularly sensitive to the reduction of retroperitoneal fat pad. The results suggested that rat strains responded differently to dietary iron inadequacy, and that FC rats were less sensitive to an iron-deficient diet as compared to the SD and WT rats. Key Words anemia, growth, iron-deficiency, rats, strain Concerning iron supplementation programs, a supplement every 3d is more efficient than daily supplementation. This finding was based on results in a Sprague-Dawley (SD) rat model of anemia (1). Some studies have used SD rats to examine the iron metabolism in iron-deficient anemia (1-3), while Fischer-344 (FC) rats have been used in studies of iron metabolism connected with iron stores in rat

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Mechanism of sex difference in rat tissue iron stores

Cited by 41 publications

References 13 publications

Iron Content of Rat Serum Ferritin.

Iron Content of Rat Serum Ferritin.

Severe iron deficiency blunts the response of the iron regulatory gene Hamp and pro-inflammatory cytokines to lipopolysaccharide

Differences in the Effect of Iron-Deficient Diet on Tissue Weight, Hemoglobin Concentration and Serum Triglycerides in Fischer-344, Sprague-Dawley and Wistar Rats.

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