scholarly journals Nonheme iron in sickle erythrocyte membranes: association with phospholipids and potential role in lipid peroxidation

Blood ◽  
1988 ◽  
Vol 72 (4) ◽  
pp. 1278-1285
Author(s):  
SA Kuross ◽  
RP Hebbel
Keyword(s):  
Lipid Peroxidation ◽  
Adenosine Diphosphate ◽  
Heme Iron ◽  
Nonheme Iron ◽  
Erythrocyte Membranes ◽  
Colored Complex ◽  
Sickle Erythrocyte ◽  
Rbc Membrane ◽  
Tenfold Excess ◽  
Additional Support

Previous studies documented the abnormal association of heme and heme proteins with the sickle RBC membrane. We have now examined RBC ghosts and inside-out membranes (IOM) for the presence of nonheme iron as detected by its formation of a colored complex with ferrozine. Sickle ghosts have 33.8 +/- 18.2 nmol nonheme iron/mg membrane protein, and sickle IOM have 4.3 +/- 3.0 nmol/mg. In contrast, normal RBC ghosts and IOM have no detectable nonheme iron. The combination of heme and nonheme iron in sickle IOM averages nine times the amount of membrane- associated iron in normal IOM. Kinetics of the ferrozine reaction show that some of this nonheme iron on IOM reacts slowly and is probably in the form of ferritin, but most (72% +/- 18%) reacts rapidly and is in the form of some other biologic chelate. The latter iron compartment is removed by deferoxamine and by treatment of IOM with phospholipase D, which suggests that it represents an abnormal association of iron with polar head groups of aminophospholipids. The biologic feasibility of such a chelate was demonstrated by using an admixture of iron with model liposomes. Even in the presence of tenfold excess adenosine diphosphate, iron partitions readily into phosphatidylserine liposomes; there is no detectable association with phosphatidylcholine liposomes. To examine the bioavailability of membrane iron, we admixed membranes and t-butylhydroperoxide and found that sickle membranes show a tenfold greater peroxidation response than do normal membranes. This is not due simply to a deficiency of vitamin E, and this is profoundly inhibited by deferoxamine. Thus, while thiol oxidation in sickle membranes previously was shown to correlate with heme iron, the present data suggest that lipid peroxidation is related to nonheme iron. In control studies, we did not find this pathologic association of nonferritin, nonheme iron with IOM prepared from sickle trait, high-reticulocyte, postsplenectomy, or iron-overloaded individuals. These data provide additional support for the concept that iron decompartmentalization is a characteristic of sickle RBCs.

scholarly journals Nonheme iron in sickle erythrocyte membranes: association with phospholipids and potential role in lipid peroxidation

Blood ◽  
1988 ◽  
Vol 72 (4) ◽  
pp. 1278-1285 ◽  
Author(s):  
SA Kuross ◽  
RP Hebbel
Keyword(s):  
Lipid Peroxidation ◽  
Adenosine Diphosphate ◽  
Heme Iron ◽  
Nonheme Iron ◽  
Erythrocyte Membranes ◽  
Colored Complex ◽  
Sickle Erythrocyte ◽  
Rbc Membrane ◽  
Tenfold Excess ◽  
Additional Support

Abstract Previous studies documented the abnormal association of heme and heme proteins with the sickle RBC membrane. We have now examined RBC ghosts and inside-out membranes (IOM) for the presence of nonheme iron as detected by its formation of a colored complex with ferrozine. Sickle ghosts have 33.8 +/- 18.2 nmol nonheme iron/mg membrane protein, and sickle IOM have 4.3 +/- 3.0 nmol/mg. In contrast, normal RBC ghosts and IOM have no detectable nonheme iron. The combination of heme and nonheme iron in sickle IOM averages nine times the amount of membrane- associated iron in normal IOM. Kinetics of the ferrozine reaction show that some of this nonheme iron on IOM reacts slowly and is probably in the form of ferritin, but most (72% +/- 18%) reacts rapidly and is in the form of some other biologic chelate. The latter iron compartment is removed by deferoxamine and by treatment of IOM with phospholipase D, which suggests that it represents an abnormal association of iron with polar head groups of aminophospholipids. The biologic feasibility of such a chelate was demonstrated by using an admixture of iron with model liposomes. Even in the presence of tenfold excess adenosine diphosphate, iron partitions readily into phosphatidylserine liposomes; there is no detectable association with phosphatidylcholine liposomes. To examine the bioavailability of membrane iron, we admixed membranes and t-butylhydroperoxide and found that sickle membranes show a tenfold greater peroxidation response than do normal membranes. This is not due simply to a deficiency of vitamin E, and this is profoundly inhibited by deferoxamine. Thus, while thiol oxidation in sickle membranes previously was shown to correlate with heme iron, the present data suggest that lipid peroxidation is related to nonheme iron. In control studies, we did not find this pathologic association of nonferritin, nonheme iron with IOM prepared from sickle trait, high-reticulocyte, postsplenectomy, or iron-overloaded individuals. These data provide additional support for the concept that iron decompartmentalization is a characteristic of sickle RBCs.

Increased severity of alcoholic liver injury in female rats: role of oxidative stress, endotoxin, and chemokines

2001 ◽  
Vol 281 (6) ◽  
pp. G1348-G1356 ◽  
Author(s):  
Amin A. Nanji ◽  
Kalle Jokelainen ◽  
Maryam Fotouhinia ◽  
Amir Rahemtulla ◽  
Peter Thomas ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Liver Injury ◽  
Fish Oil ◽  
Nonheme Iron ◽  
Female Rats ◽  
Male Rats ◽  
Mrna Levels ◽  
Alcoholic Liver Injury ◽  
Tnf Α ◽  
Cox 2

Alcoholic liver injury is more severe and rapidly developing in women than men. To evaluate the reason(s) for these gender-related differences, we determined whether pathogenic mechanisms important in alcoholic liver injury in male rats were further upregulated in female rats. Male and age-matched female rats (7/group) were fed ethanol and a diet containing fish oil for 4 wk by intragastric infusion. Dextrose isocalorically replaced ethanol in control rats. We analyzed liver histopathology, lipid peroxidation, cytochrome P-450 (CYP)2E1 activity, nonheme iron, endotoxin, nuclear factor-κB (NF-κB) activation, and mRNA levels of cyclooxygenase-1 (COX-1) and COX-2, tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-2 (MIP-2). Alcohol-induced liver injury was more severe in female vs. male rats. Female rats had higher endotoxin, lipid peroxidation, and nonheme iron levels and increased NF-κB activation and upregulation of the chemokines MCP-1 and MIP-2. CYP2E1 activity and TNF-α and COX-2 levels were similar in male and female rats. Remarkably, female rats fed fish oil and dextrose also showed necrosis and inflammation. Our findings in ethanol-fed rats suggest that increased endotoxemia and lipid peroxidation in females stimulate NF-κB activation and chemokine production, enhancing liver injury. TNF-α and COX-2 upregulation are probably important in causing liver injury but do not explain gender-related differences.

scholarly journals Total and Nonheme Dietary Iron Intake Is Associated with Metabolic Syndrome and Its Components in Chinese Men and Women

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1663 ◽  
Author(s):  
Zhenni Zhu ◽  
Fan Wu ◽  
Ye Lu ◽  
Chunfeng Wu ◽  
Zhengyuan Wang ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Serum Ferritin ◽  
Smoking Status ◽  
Heme Iron ◽  
Nonheme Iron ◽  
Total Iron ◽  
Positive Trend ◽  
Dietary Iron ◽  
Iron Intake ◽  
Men And Women

The causal relationship between serum ferritin and metabolic syndrome (MetS) remains inconclusive. Dietary iron intake increases serum ferritin. The objective of this study was to evaluate associations of total, heme, and nonheme dietary iron intake with MetS and its components in men and women in metropolitan China. Data from 3099 participants in the Shanghai Diet and Health Survey (SDHS) obtained during 2012–2013 were included in this analysis. Dietary intake was assessed by 24-h diet records from 3 consecutive days. Multivariate generalized linear mixed models were used to evaluate the associations of dietary iron intake with MetS and its components. After adjustment for potential confounders as age, sex, income, physical exercise, smoking status, alcohol use, and energy intake, a positive trend was observed across quartiles of total iron intake and risk of MetS (p for trend = 0.022). Compared with the lowest quartile of total iron intake (<12.72 mg/day), the highest quartile (≥21.88 mg/day) had an odds ratio (95% confidence interval), OR (95% CI), of 1.59 (1.15,2.20). In addition, the highest quartile of nonheme iron intake (≥20.10 mg/day) had a 1.44-fold higher risk of MetS compared with the lowest quartile (<11.62 mg/day), and higher risks of MetS components were associated with the third quartiles of total and nonheme iron intake. There was no association between heme iron intake and risk of MetS (p for trend = 0.895). Associations for total and nonheme iron intake with MetS risk were found in men but not in women. Total and nonheme dietary iron intake was found to be positively associated with MetS and its components in the adult population in metropolitan China. This research also revealed a gender difference in the association between dietary iron intake and MetS.

Effect of Cu2+-ascorbic acid on lipid peroxidation, Mg2+-ATPase activity and spectrin of RBC membrane and reversal by erythropoietin

1992 ◽  
Vol 118 (1) ◽  
pp. 23-30 ◽  
Author(s):  
Aindrila Chattopadhyay ◽  
Tapasi Das Choudhury ◽  
Mukul K. Basu ◽  
Asoke G. Datta
Keyword(s):  
Lipid Peroxidation ◽  
Ascorbic Acid ◽  
Atpase Activity ◽  
Rbc Membrane

Further investigation of methylation on sickle erythrocyte membranes

1983 ◽  
Vol 30 (3) ◽  
pp. 342-348 ◽  
Author(s):  
Jai-Youl Ro ◽  
Barbara Neilan ◽  
Sangduk Kim
Keyword(s):  
Erythrocyte Membranes ◽  
Sickle Erythrocyte

Food iron absorption in idiopathic hemochromatosis

Blood ◽  
1989 ◽  
Vol 74 (6) ◽  
pp. 2187-2193 ◽  
Author(s):  
SR Lynch ◽  
BS Skikne ◽  
JD Cook
Keyword(s):  
Serum Ferritin ◽  
Iron Absorption ◽  
Iron Status ◽  
Normal Subjects ◽  
Heme Iron ◽  
Nonheme Iron ◽  
Ferritin Concentration ◽  
Normal Volunteers ◽  
Idiopathic Hemochromatosis ◽  
The Relationship

Abstract The relationship between iron status and food iron absorption was evaluated in 75 normal volunteers, 15 patients with idiopathic hemochromatosis, and 22 heterozygotes by using double extrinsic radioiron tags to label independently the nonheme and heme iron components of a hamburger meal. In normal subjects, absorption from each of these pools was inversely correlated with storage iron, as measured by the serum ferritin concentration. In patients with hemochromatosis, absorption of both forms of iron was far greater than would be predicted from the relationship between absorption and serum ferritin observed in normal volunteers. Nevertheless, there was still a modest but statistically significant reduction in absorption of nonheme iron with increasing serum ferritin. This relationship could not be demonstrated in the case of heme iron absorption. In heterozygotes, nonheme iron absorption from a hamburger meal containing no supplementary iron did not differ significantly from that observed in normal volunteers. However, when this meal was both modified to promote bioavailability and supplemented with iron, absorption of nonheme iron was significantly elevated. These studies confirm the presence of excessive nonheme iron absorption even from unfortified meals in patients with idiopathic hemochromatosis and suggest in addition that they are particularly susceptible to iron loading from diets containing a high proportion of heme iron. Impaired regulation of nonheme iron absorption was also observed in heterozygous individuals, but a statistically significant abnormality was demonstrable only when the test meal contained a large highly bioavailable iron supplement.

scholarly journals Comparison of Antioxidants: The Limited Correlation between Various Assays of Antioxidant Activity

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3244
Author(s):  
Katarzyna Naparło ◽  
Mirosław Soszyński ◽  
Grzegorz Bartosz ◽  
Izabela Sadowska-Bartosz
Keyword(s):  
Reactive Oxygen Species ◽  
Lipid Peroxidation ◽  
Antioxidant Activity ◽  
Free Radical ◽  
Experimental System ◽  
Natural Antioxidants ◽  
Egg Yolk ◽  
Erythrocyte Membranes ◽  
Oxygen Species ◽  
Inhibitory Effects

The inhibitory effects a range of synthetic and natural antioxidants on lipid peroxidation of egg yolk and erythrocyte membranes induced by a free radical generator 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH) was compared, with significant differences being found between both systems. When the protection by selected antioxidants against the effects of AAPH on erythrocytes (hemolysis, oxidation of hemoglobin and glutathione (GSH) and generation of reactive oxygen species (ROS)) was studied, most antioxidants were protective, but in some tests (oxidation of hemoglobin and GSH) some acted as prooxidants, inducing oxidation in the absence of AAPH and enhancing the AAPH-induced oxidation. These results demonstrate a diversified action of antioxidants in different systems and point to a need for careful extrapolation of any conclusions drawn from one parameter or experimental system to another.

High specific activity heme-Fe and its application for studying heme-Fe metabolism in Caco-2 cell monolayers

2002 ◽  
Vol 283 (5) ◽  
pp. G1125-G1131 ◽  
Author(s):  
Jennifer R. Follett ◽  
Yasushi A. Suzuki ◽  
Bo Lönnerdal
Keyword(s):  
Iron Absorption ◽  
Specific Activity ◽  
Iron Status ◽  
Basolateral Membrane ◽  
High Specific Activity ◽  
Heme Iron ◽  
Nonheme Iron ◽  
Serum Free Medium ◽  
Factors Affecting ◽  
Cell Monolayers

Heme-Fe is an important source of dietary iron in humans. Caco-2 cells have been used extensively to study human iron absorption with an emphasis on factors affecting nonheme iron absorption. Therefore, we examined several factors known to affect heme iron absorption. Cells grown in bicameral chambers were incubated with high specific activity [59Fe]heme alone or with 1% globin, BSA, or fatty acid-free BSA (BSA-FA) to examine the effect of protein source on absorption. Heme iron absorption was enhanced by globin and inhibited by BSA and BSA-FA. Absorption of heme iron in cells pretreated for 7 days with serum-free medium containing 1, 25, 50, or 100 μM Fe was higher in the 1-μM-Fe pretreatment group than in all other groups ( P < 0.05), showing an effect of iron status. Increased heme concentrations resulted in decreased percent absorbed but increased total heme iron absorption and increased transport rate across the basolateral membrane. Finally, cells treated with 10 μM CdCl2, which induces heme oxygenase, demonstrated higher absorption of [59Fe]heme than control cells ( P < 0.05). Our results from Caco-2 cells are in agreement with human studies and make this a promising model for examining intestinal heme iron absorption.

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