Redox Active Iron at the Center of Oxidative Stress in Alzheimer Disease

2005 ◽  
Vol 2 (6) ◽  
pp. 479-482 ◽  
Author(s):  
Kazuhiro Honda ◽  
Paula Moreira ◽  
Quan Liu ◽  
Sandra Siedlak ◽  
Xiongwei Zhu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer Disease ◽  
Active Iron ◽  
Redox Active

In vitro study on the effects of iron sucrose, ferric gluconate and iron dextran on redox-active iron and oxidative stress

2011 ◽  
Vol 60 (07) ◽  
pp. 459-465
Author(s):  
Brigitte Sturm ◽  
Hannes Steinkellner ◽  
Nina Ternes ◽  
Hans Goldenberg ◽  
Barbara Scheiber-Mojdehkar
Keyword(s):  
Oxidative Stress ◽  
In Vitro Study ◽  
Iron Sucrose ◽  
Vitro Study ◽  
Iron Dextran ◽  
Active Iron ◽  
Redox Active ◽  
And Oxidative Stress

Oxidative Stress and Vaso-Occlusion in Sickle Cell Disease: Role of Activated Leukocytes and Redox Active Iron.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3165-3165 ◽  
Author(s):  
John D. Belcher ◽  
Hemachandra Mahaseth ◽  
Thomas E. Welch ◽  
Felix Boakye-Agyeman ◽  
Robert P. Hebbel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Sickle Cell Disease ◽  
Blood Cell ◽  
Sickle Cell ◽  
Ambient Air ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Active Iron ◽  
Redox Active ◽  
Hypoxia Reoxygenation

Abstract Sickle cell disease (SCD) is a disease of oxidative stress. We and others have demonstrated increased oxidative stress, inflammation, endothelial cell activation and white blood cell counts in human patients and transgenic murine models of SCD. Leukocytosis in SCD is associated with increases in the incidence of pain crisis, acute chest syndrome, stroke and mortality. We hypothesize that reactive oxygen species (ROS) derived from leukocytes and excess redox active iron promote vascular inflammation and vaso-occlusion. Leukocytes were activated in S+S-Antilles sickle mice compared to normal C57BL/6 control mice as measured by the percentage of leukocytes expressing CD11b on their surface in ambient air (25.4% vs. 19.3%, p<0.05) and after exposure of mice to hypoxia-reoxygenation (31.7% vs. 23.0%, p<0.05). In addition, resting leukocytes from S+S-Antilles mice produce 1.8-fold more H2O2 than normal mice (p<0.05) as measured by Amplex Red (10-acetyl-3,7-dihydroxyphenoxazine) fluorescence. These leukocyte oxidants are especially toxic in the presence of excess redox active iron. Histopathology of the lungs and livers of 10 week old S+S-Antilles and BERK sickle mice showed red blood cell (RBC) congestion compared to normal. In addition, the sickle livers had multiple areas of infarction and inflammatory leukocyte infiltration. The heme contents of S+S-Antilles sickle lungs and livers were increased by 37- and 4.9-fold, respectively, compared to normals (p<0.05 for both organs). Furthermore, there was significantly more chelatable iron that is potentially redox active as measured by Ferene-S in sickle lungs (21.0-fold, p<0.05) and livers (2.4-fold, p<0.05) compared to normals. Thus, these data demonstrate there is an explosive pro-oxidative environment in sickle mice. These excess oxidants lead to NF-kB activation, VCAM-1 and ICAM-1 expression, and increased oxidative injury, as seen histopathologically by nitro-tyrosine and dihydroethidium staining in organs. Hypoxia-reoxygenation, which induces RBC sickling and enhances ROS production in sickle mice, causes an increase in leukocyte rolling (4.4-fold, S+S-Antilles vs. normal, p<0.05) and adhesion (6.5-fold, p<0.05). Hypoxia-reoxygenation induces transient vaso-occlusion in 12% and 24% of the subcutaneous venules of S+S-Antilles and BERK mice respectively. No vessels become static in normal mice (p<0.05 sickle vs. normal). Hypoxia-reoxygenation-induced vaso-occlusion can be inhibited by antibodies to P-selectin, VCAM-1 or ICAM-1. Furthermore, scavenging ROS with the SOD and catalase mimetic, polynitroxyl albumin or the iron chelator Trimidox, inhibited hypoxia-reoxygenation-induced vaso-occlusion (p<0.05). We conclude that oxidative stress derived from activated leukocytes and excess redox active iron plays a critical role in promoting vaso-occlusion and organ injury in SCD. We speculate that iron chelators, leukocyte adhesion molecule blockade and anti-oxidants will modulate vaso-occlusion in patients with SCD.

Lysosomal Redox-Active Iron Is Important for Oxidative Stress-Induced DNA Damage

2004 ◽  
Vol 1019 (1) ◽  
pp. 285-288 ◽  
Author(s):  
TINO KURZ ◽  
ALAN LEAKE ◽  
THOMAS ZGLINICKI ◽  
ULF T. BRUNK
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Active Iron ◽  
Redox Active

scholarly journals Vitamin E Attenuates Oxidative Stress Induced by Intravenous Iron in Patients on Hemodialysis

2000 ◽  
Vol 11 (3) ◽  
pp. 539-549
Author(s):  
JOHANNES M. ROOB ◽  
GHOLAMALI KHOSCHSORUR ◽  
ANDREAS TIRAN ◽  
JÖRG H. HORINA ◽  
HERWIG HOLZER ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Vitamin E ◽  
Oral Dose ◽  
Single Oral Dose ◽  
Intravenous Iron ◽  
Hemodialysis Session ◽  
Active Iron ◽  
Redox Active ◽  
Vitamin E Supplementation

Abstract. Intravenous iron application to anemic patients on hemodialysis leads to an “oversaturation” of transferrin. As a result, non-transferrin-bound, redox-active iron might induce lipid peroxidation. To test the hypothesis that vitamin E attenuates lipid peroxidation in patients receiving 100 mg of iron(II) hydroxide sucrose complex intravenously during a hemodialysis session, 22 patients were investigated in a randomized cross-over design, either with or without a single oral dose of 1200 IU of all-rac-α-tocopheryl acetate taken 6 h before the hemodialysis session. Blood was drawn before and 30, 60, 90, 135, and 180 min after the start of the iron infusion, and areas under the curve (AUC0-180 min) of ratios of plasma malondialdehyde (MDA) to cholesterol and plasma total peroxides to cholesterol (two markers of lipid peroxidation) were determined as the outcome variables. At baseline of the session without vitamin E supplementation, plasma α-tocopherol concentrations (27.6 ± 1.8 μmol/L) and ratios of α-tocopherol to cholesterol (5.88 ± 1.09 mmol/mol) were normal, plasma MDA concentrations were above normal (1.20 ± 0.28 μmol/L), and bleomycin-detectable iron (BDI), indicating the presence of redox-active iron, was not detectable. Upon iron infusion, BDI and MDA concentrations increased significantly (P < 0.001). BDI concentrations explained the increase over baseline in MDA concentrations (MDA = 1.29 + 0.075 × BDI). Vitamin E supplementation, leading to a 68% increase in plasma α-tocopherol concentrations, significantly reduced the AUC0-180 min of MDA to cholesterol (P = 0.004) and peroxides to cholesterol (P = 0.002). These data demonstrate that a single oral dose of vitamin E attenuates lipid peroxidation in patients on hemodialysis receiving intravenous iron. Given that intravenous iron is applied repeatedly to patients on hemodialysis, this therapeutic approach may protect against oxidative stress-related degenerative disease in the long term.

Is increased redox-active iron in Alzheimer disease a failure of the copper-binding protein ceruloplasmin?

1999 ◽  
Vol 26 (11-12) ◽  
pp. 1508-1512 ◽  
Author(s):  
Rudy J Castellani ◽  
Mark A Smith ◽  
Akihiko Nunomura ◽  
Peggy L.R Harris ◽  
George Perry
Keyword(s):  
Alzheimer Disease ◽  
Binding Protein ◽  
Copper Binding ◽  
Active Iron ◽  
Redox Active ◽  
Copper Binding Protein

Abstract 343: Induction of Apoptosis in Human Macrophages by 7-ketocholesterol and Iron Ascorbate

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Deborah A Leonard ◽  
Ashley M Scofield ◽  
Robert S Greene
Keyword(s):  
Oxidative Stress ◽  
Synergistic Effects ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Parp Cleavage ◽  
Acute Monocytic Leukemia ◽  
Mrna Levels ◽  
Monocytic Leukemia ◽  
Active Iron ◽  
Redox Active

Inflammation is the new paradigm for the development and progression of atherosclerotic lesions in coronary artery disease. Factors that increase oxidative stress and apoptosis of cells within the lesion contribute to sustaining the inflammatory response. It was hypothesized that redox-active iron and oxysterols, which have both been found in association with atherosclerotic plaques, contribute to oxidative stress and apoptosis by distinct, but overlapping signaling pathways. The human acute monocytic leukemia cell line THP-1 was used as a model system to study the roles of redox-active iron and 7-ketocholesterol in macrophage apoptosis. The ability of both reagents to induce apoptosis in THP-1 macrophages was demonstrated using flow cytometry. The kinetics of poly(ADP-ribose) polymerase (PARP) cleavage as measured by ELISA were also similar. qRT-PCR was used to measure mRNA levels of several pro- and anti-apoptotic genes. While 7-ketocholesterol increased the level of CHOP mRNA (a transcription factor in endoplasmic reticulum (ER)-initiated apoptosis), there was no similar increase in response to iron ascorbate treatment. Expression of other markers of ER stress, like the transcription factors ATF3 and CEBPbeta, was increased by both compounds, but the timing of changes in gene expression was different. TNFalpha regulates both apoptosis and inflammatory cytokine production. Macrophages are major producers of TNFalpha as well as being highly responsive to the cytokine. A comparison of the changes in TNFalpha mRNA and protein levels in response to iron ascorbate and 7-ketocholesterol suggested that while ERK1/2 and NFkB signaling are important in TNFalpha expression, differentially regulated post-transcriptional processes determine the release of TNFalpha by macrophages. These preliminary results suggest that the apoptotic pathways activated by oxysterols and redox-active iron may be different and that these compounds may have additive or synergistic effects on lesion progression.

REDOX-ACTIVE IRON IS ASSOCIATED WITH THE PATHOLOGICAL LESIONS IN ALZHEIMER DISEASE

1997 ◽  
Vol 56 (5) ◽  
pp. 608 ◽  
Author(s):  
Mark A. Smith ◽  
Peggy L.R. Harris ◽  
Lawrence M. Savre ◽  
Georce Perry
Keyword(s):  
Alzheimer Disease ◽  
Pathological Lesions ◽  
Active Iron ◽  
Redox Active

scholarly journals Iron: The Redox-active Center of Oxidative Stress in Alzheimer Disease

2007 ◽  
Vol 32 (10) ◽  
pp. 1640-1645 ◽  
Author(s):  
Rudy J. Castellani ◽  
Paula I. Moreira ◽  
Gang Liu ◽  
Jon Dobson ◽  
George Perry ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer Disease ◽  
Active Center ◽  
Redox Active

scholarly journals Ribosomal RNA in Alzheimer Disease Is Oxidized by Bound Redox-active Iron

2005 ◽  
Vol 280 (22) ◽  
pp. 20978-20986 ◽  
Author(s):  
Kazuhiro Honda ◽  
Mark A. Smith ◽  
Xiongwei Zhu ◽  
Diane Baus ◽  
William C. Merrick ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Ribosomal Rna ◽  
Active Iron ◽  
Redox Active
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