Contribution of redox-active iron and copper to oxidative damage in Alzheimer disease

2004 ◽  
Vol 3 (3) ◽  
pp. 319-326 ◽  
Author(s):  
Rudy J Castellani ◽  
Kazuhiro Honda ◽  
Xiongwei Zhu ◽  
Adam D Cash ◽  
Akihiko Nunomura ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Oxidative Damage ◽  
Active Iron ◽  
Redox Active

scholarly journals Relocalized redox-active lysosomal iron is an important mediator of oxidative-stress-induced DNA damage

2004 ◽  
Vol 378 (3) ◽  
pp. 1039-1045 ◽  
Author(s):  
Tino KURZ ◽  
Alan LEAKE ◽  
Thomas von ZGLINICKI ◽  
Ulf T. BRUNK
Keyword(s):  
Dna Damage ◽  
Free Radical ◽  
Oxidative Damage ◽  
Nuclear Dna ◽  
Membrane Integrity ◽  
Lysosomal Hydrolases ◽  
Free Radical Biol ◽  
Active Iron ◽  
Vacuolar Compartment ◽  
Redox Active

Oxidative damage to nuclear DNA is known to involve site-specific Fenton-type chemistry catalysed by redox-active iron or copper in the immediate vicinity of DNA. However, the presence of transition metals in the nucleus has not been shown convincingly. Recently, it was proposed that a major part of the cellular pool of loose iron is confined within the acidic vacuolar compartment [Yu, Persson, Eaton and Brunk (2003) Free Radical Biol. Med. 34, 1243–1252; Persson, Yu, Tirosh, Eaton and Brunk (2003) Free Radical Biol. Med. 34, 1295–1305]. Consequently, rupture of secondary lysosomes, as well as subsequent relocation of labile iron to the nucleus, could be an important intermediary step in the generation of oxidative damage to DNA. To test this concept we employed the potent iron chelator DFO (desferrioxamine) conjugated with starch to form an HMM-DFO (high-molecular-mass DFO complex). The HMM-DFO complex will enter cells only via fluid-phase endocytosis and remain within the acidic vacuolar compartment, thereby chelating redox-active iron exclusively inside the endosomal/lysosomal compartment. Both free DFO and HMM-DFO equally protected lysosomal-membrane integrity against H2O2-induced oxidative disruption. More importantly, both forms of DFO prevented H2O2-induced strand breaks in nuclear DNA, including telomeres. To exclude the possibility that lysosomal hydrolases, rather than iron, caused the observed DNA damage, limited lysosomal rupture was induced using the lysosomotropic detergent O-methyl-serine dodecylamine hydrochloride; subsequently, hardly any DNA damage was found. These observations suggest that rapid oxidative damage to cellular DNA is minimal in the absence of redox-active iron and that oxidant-mediated DNA damage, observed in normal cells, is mainly derived from intralysosomal iron translocated to the nucleus after lysosomal rupture.

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

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

Release of free, redox-active iron in the liver and DNA oxidative damage following phenylhydrazine intoxication

1997 ◽  
Vol 53 (11) ◽  
pp. 1743-1751 ◽  
Author(s):  
Marco Ferrali ◽  
Cinzia Signorini ◽  
Lidia Sugherini ◽  
Alfonso Pompella ◽  
Maura Lodovici ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Dna Oxidative Damage ◽  
Active Iron ◽  
Redox Active

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 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

scholarly journals Iron-Mediated Lysosomal Membrane Permeabilization in Ethanol-Induced Hepatic Oxidative Damage and Apoptosis: Protective Effects of Quercetin

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Yanyan Li ◽  
Man Chen ◽  
Yanyan Xu ◽  
Xiao Yu ◽  
Ting Xiong ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Membrane Permeabilization ◽  
Lysosomal Membrane ◽  
Protective Effects ◽  
Lysosomal Membrane Permeabilization ◽  
Active Iron ◽  
Redox Active ◽  
Chronic Ethanol Consumption ◽  
Continuous Decomposition ◽  
Alcoholic Liver Diseases

Iron, in its free ferrous states, can catalyze Fenton reaction to produceOH∙, which is recognized as a crucial role in the pathogenesis of alcoholic liver diseases (ALD). As a result of continuous decomposition of iron-containing compounds, lysosomes contain a pool of redox-active iron. To investigate the important role of intralysosomal iron in alcoholic liver injury and the potential protection of quercetin, male C57BL/6J mice fed by Lieber De Carli diets containing ethanol (30% of total calories) were cotreated by quercetin or deferoxamine (DFO) for 15 weeks and ethanol-incubated mice primary hepatocytes were pretreated with FeCl3, DFO, and bafilomycin A1 at their optimal concentrations and exposure times. Chronic ethanol consumption caused an evident increase in lysosomal redox-active iron accompanying sustained oxidative damage. Iron-mediated ROS could trigger lysosomal membrane permeabilization (LMP) and subsequent mitochondria apoptosis. The hepatotoxicity was attenuated by reducing lysosomal iron while being exacerbated by escalating lysosomal iron. Quercetin substantially alleviated the alcoholic liver oxidative damage and apoptosis by decreasing lysosome iron and ameliorating iron-mediated LMP, which provided a new prospective of the use of quercetin against ALD.

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

Abstract T P351: Unbound Iron and Ceruloplasmin Levels in Cerebrospinal Fluid Are Associated with Development of Deep Cerebral Infarcts Following Subarachnoid Hemorrhage

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Lauren Koffman ◽  
Gabor Toth ◽  
M. Shazam Hussain ◽  
Magdy Selim ◽  
Peter Rasmussen ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Infarcts ◽  
Active Iron ◽  
Redox Active ◽  
Wilcoxon Rank Sum Test ◽  
Radiological Data ◽  
Experimental Subarachnoid Hemorrhage ◽  
Preliminary Study ◽  
Iron Redox

Introduction: Iron-dependent formation of reactive oxygen species has been implicated in the development of vasospasm (VSP) and neuronal injury following experimental subarachnoid hemorrhage (SAH). We report the association between unbound (“free”) iron in CSF of SAH patients and the risk of angiographic vasospasm and cerebral infarcts (CI) on neuroimaging from a recently completed pilot study. Methods: Samples of cerebrospinal fluid (CSF) were obtained on days 1, 3, and 5. A fluorometric assay that relies on an oxidation sensitive probe was used to measure redox active iron (REDOX-Fe). Ceruloplasmin (Cp) concentration and levels of malondialdehyde (MDA), a marker of lipid peroxidation were also measured. We prospectively collected and recorded demographic, clinical, and radiological data. Logistic regression and Wilcoxon Rank Sum test were used. Results: Five of 12 patients developed angiographic VSP (41.6%) and eight developed CI (66.6%). Mean REDOX-Fe was higher in patients with CI (3.96 ± 0.97 Vs. 2.77 ± 0.87 mcg/dl, p 0.07), particularly in patients with deep-seated strokes (4.56 ± 0.67 Vs. 3.35 ± 0.89, p 0.03). Levels of Cp at day 3 were lower in patients with deep strokes (34,092 ± 23,780 Vs. 86,045 ± 34,752 ng/ml, p 0.03). A trend towards higher REDOX-Fe on day 3 in patients who developed VSP (4.52 ± 1.16 Vs. 2.96 ± 0.71, p 0.07), and lower Cp levels on day 5 (45,033 ± 29,079 Vs. 63,044 ± 24,821, p 0.1) was found. Levels of MDA were higher in patients who developed CI (10.36 ± 4.36 Vs. 5.9 ± 4.2 nmol, p 0.08). Conclusions: In this preliminary study we found higher concentrations of redox active iron in CSF of SAH patients who develop deep-seated CI on neuroimaging. Evidence of increased oxidative damage correlated with development of CI. A possible association between non-protein bound iron and angiographic VSP is suggested as well. Ceruloplasmin may exert a protective effect in this setting. Further studies are needed to validate these findings.

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