Structural differences in ferritins from normal and malignant rat tissues

Linder, Maria C.; Moor, Joan R.; Munro, Hamish N.; Morris, Harold P.

doi:10.1016/0005-2795(75)90284-6

Cited by 33 publications

(10 citation statements)

References 23 publications

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“…Serum and tissue ferritins are not identical in their iron contents or electrophoretic mobilities . A wide range of isoferritins exists in health and disease, with the more basic ferritins predominating in iron overload and the acidic ferritins in malignancy (Richter, 1965;Makino & Konno, 1969;Alpert et nl, 1973;Drysdale & Singer, 1974;Linder et al, 1975) and it is indeed feasible that different isoferritins may have varying degrees of immunosuppressive activity. Nevertheless, the demonstration of an obvious in vitro immunosuppressive effect of ferritin a t concentrations similar to those encountered in the peripheral blood in certain disorders appears to open a new avenue in the search for the causes of impaired cell mediated immunity in malignant diseases.…”

Section: Discussionmentioning

confidence: 99%

Suppressive Effect of Ferritin on in Vitro Lymphocyte Function

et al. 1979

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This study describes the effect of ferritin on lymphocyte function in vitro. Peripheral blood lymphocytes isolated from normal donors were incubated with purified human splenic ferritin, and the mitogenic effect of phytohaemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM) and mixed lymphocyte reaction (MLR) were assessed by the uptake of 3H-thymidine (3H-TdR). Ferritin (0.25--5.0 micrograms/ml culture) caused a marked suppression of PHA nad Con A blastogenesis but had no suppressive effect on PWM-induced transformation. Maximal suppression was obtained at a ferritin concentration of 1 microgram/ml and this was not enhanced by increasing ferritin concentrations. Ferritin also reduced the Con A capping phenomenon in normal lymphocytes from 22% to 6%, suppressed the MLR reaction but had no effect on the ability of normal lymphocytes to form E, EA and EAC rosettes or on in vitro lymphocyte cytoxicity against the K-562 cell line. Visual proof of the suppressive effect of ferritin on mitogen induced blastogenesis was provided by scanning electron microscopy, and direct evidence for the ability of lymphocytes to bind ferritin was obtained from studies with radioiodine labelled ferritin. The above findings indicate that ferritin suppresses certain parameters of T-lymphocyte function in vitro. The relation of the present findings to recognized abnormalities of T-cell function encountered in certain neoplastic disorders associated with high serum ferritin levels is at present unknown.

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Section: Discussionmentioning

confidence: 99%

Suppressive Effect of Ferritin on in Vitro Lymphocyte Function

et al. 1979

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“…It has been estimated that up to 4500 atoms of Fe can be accommodated within a single 24 subunit molecule, although the average Fe content (at least in liver and spleen cells) tends to be about half of that or less [23,24]. Ferritin from non-hepatic tissues, as well as cancers, tend to have a lower iron content [25,26]. The iron content of individual ferritin molecules covers a wide range; some molecules have much and others little or no iron.…”

Section: Ferritin Structure and Formation For Iron Storage And Detmentioning

confidence: 99%

Mobilization of Stored Iron in Mammals: A Review

Linder

2013

Nutrients

105

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From the nutritional standpoint, several aspects of the biochemistry and physiology of iron are unique. In stark contrast to most other elements, most of the iron in mammals is in the blood attached to red blood cell hemoglobin and transporting oxygen to cells for oxidative phosphorylation and other purposes. Controlled and uncontrolled blood loss thus has a major impact on iron availability. Also, in contrast to most other nutrients, iron is poorly absorbed and poorly excreted. Moreover, amounts absorbed (~1 mg/day in adults) are much less than the total iron (~20 mg/day) cycling into and out of hemoglobin, involving bone marrow erythropoiesis and reticuloendothelial cell degradation of aged red cells. In the face of uncertainties in iron bioavailability, the mammalian organism has evolved a complex system to retain and store iron not immediately in use, and to make that iron available when and where it is needed. Iron is stored innocuously in the large hollow protein, ferritin, particularly in cells of the liver, spleen and bone marrow. Our current understanding of the molecular, cellular and physiological mechanisms by which this stored iron in ferritin is mobilized and distributed—within the cell or to other organs—is the subject of this review.

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“…Liver neoplastic cells have been shown not to be altered in their uptake of iron (29). Presumably, therefore, a defect in structure or expression of ferritin, which is essential for iron metabolism (30)(31)(32)(33)(34)(35), may be involved.…”

Section: Toxicologic Pathologymentioning

confidence: 99%

Abnormalities in Liver Iron Accumulation During N-2-Fluorenylacetamide Hepatocarcinogenesis that are Dependent or Independent of Continued Carcinogen Action

1984

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The characteristics of liver iron accumulation were studied during N-2-fluorenylacetamide (FAA)-induced hepatocarcinogenesis in rats. After injection of iron-dextran i n control rats, hepatocytes accumulated stainable iron evenly through.out hepatic lobules. During the feeding of FAA, iron accumulation was reduced in the midzonal and centriiobular regions. After FAA removal, hepatocytes in these regions again accumulated high amounts of iron. Hepatocellular altered foci induced by FAA displayed rather uniform (> 94%) iron-exclusion during FAA feeding. After FAA removal, however, iron-exc'lusion was lost i n a fraction of the foci, while others (40-64%) remained resistant to iron accumulation. A large majority of liver neoplasms (> 93%) displayed resistance to cellular iron accumulation both during FAA feeding and after removal of FAA. Thus, iron-exclusion by liver neoplasms i s carcinogen-independent and irreversible, in contrast with that of normal hepatocytes which is completely carcinogen-dependent and reversible. Altered foci appear to represent two populations: one is characterized by reversible iron-exclusion whereas the other, like neoplasms, possesses permanent iron-exclusion.

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Structural differences in ferritins from normal and malignant rat tissues

Cited by 33 publications

References 23 publications

Suppressive Effect of Ferritin on in Vitro Lymphocyte Function

Suppressive Effect of Ferritin on in Vitro Lymphocyte Function

Mobilization of Stored Iron in Mammals: A Review

Abnormalities in Liver Iron Accumulation During N-2-Fluorenylacetamide Hepatocarcinogenesis that are Dependent or Independent of Continued Carcinogen Action

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