The Molecular Pathobiology of Cell Membrane Iron: The Sickle Red Cell as a Model

Browne, Paul; Shalev, Oded; Hebbel, Robert P.

doi:10.1016/s0891-5849(97)00391-2

Cited by 85 publications

(57 citation statements)

References 60 publications

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“…Oxidized hemoglobin forms which are unstable and easily denatured are found deposited together with free heme and iron on the cytosolic face of the erythrocyte membrane [6].…”

Section: Introductionmentioning

confidence: 99%

Up-regulation of α1-microglobulin by hemoglobin and reactive oxygen species in hepatoma and blood cell lines

Olsson

Maria

Olofsson

et al. 2007

Free Radical Biology and Medicine

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“…Oxidized hemoglobin forms which are unstable and easily denatured are found deposited together with free heme and iron on the cytosolic face of the erythrocyte membrane [6].…”

Section: Introductionmentioning

confidence: 99%

Up-regulation of α1-microglobulin by hemoglobin and reactive oxygen species in hepatoma and blood cell lines

Olsson

Maria

Olofsson

et al. 2007

Free Radical Biology and Medicine

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“…SS RBCs produce membrane-associated hemin secondary to repeated formation of sickle hemoglobin polymers. This hemin (free ferriprotoporphyrin IX (FP) moieties) in oxyhemoglobin is oxidized from the Fe(II) state to the Fe(III) state with the consequent production of a half-molar equivalent of H 2 O 2 -a potentially toxic molecule [10,11]. Alternative detoxication pathways, including the binding to FP-binding proteins, reaction with glutathione, and FP degradation, may also contribute to FP detoxification [12].…”

Section: Introductionmentioning

confidence: 99%

Spectrin's E2/E3 ubiquitin conjugating/ligating activity is diminished in sickle cells

2005

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Erythrocyte spectrin contains E2/E3 ubiquitin conjugating/ligating activity in its a subunit. Ankyrin is a target of spectrin's E2/E3 ubiquitin conjugating/ligating activity in vitro and in vivo. We compare the ubiquitination levels of ankyrin mediated by control and sickle cell spectrin using a biotinylated ubiquitin cell-free assay. Sickle cell spectrin has diminished ability to transfer ubiquitin from an intermediate spectrin-ubiquitin thioester adduct (a 0 spectrin) to ankyrin, which may be due to glutathiolation of spectrin's E2 and/ or E3 active site cysteines. There is also a diminished ability of the sickle cell ankyrin to serve as target of spectrin's E2/E3 activity, probably due to oxidative damage to ankyrin. A direct correlation exists between the a 0 /a spectrin ratio and spectrin's ability to ubiquitinate ankyrin. There is also an inverse correlation between severity of the disease and the a 0 /a spectrin ratio in SS erythrocytes. These results suggest that reduced spectrin E2/ E3 activity is an important determinant of sickle cell severity. Am. J. Hematol. 79:89-96, 2005.

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“…We showed similar oxidantinitiated conversion of the chromophore in BODIPY 581/591-PC from red-to-green fluorescing forms using spectrofluometric, flow cytometric, and confocal microscope-based assays. FP-FeIII was needed to catalyze t-BHP-mediated oxidation in pure lipid or detergent systems; however, in intact RBCs, hemoglobin or a hemoglobin breakdown product catalyzed the oxidation events (57). HPLC analysis confirmed the production of lipid hydroperoxides during t-BHP treatment of ghosts.…”

Section: Discussionmentioning

confidence: 92%

A phosphatidylcholine‐BODIPY 581/591 conjugate allows mapping of oxidative stress in P. falciparum‐infected erythrocytes

Klonis

Suarna

et al. 2009

Cytometry Pt A

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The chromophore, BODIPY 581/591, has an extended conjugated system that reacts with oxygen centered-radicals leading to changes in its spectral characteristics. Fatty acid-conjugated BODIPY 581/591 transfers readily between membrane bilayers and can be used as a sensor of oxidative stress in cell populations. We report here the use of a phosphatidylcholine (PC) derivative of BODIPY 581/591, which transfers much less rapidly between membranes. This allows the analysis of oxidative stress in individual cells and in different compartments within cells. Quantitative imaging and flow cytometry were used to measure the ratio of fully conjugated to oxidized probe in model systems and in Plasmodium falciparum-infected erythrocytes. We observed an increase in the oxidation of the parasite-associated BODIPY 581/591-PC as the intraerythrocytic parasite matures. By contrast, BODIPY 581/591-PC associated with the erythrocyte membrane experiences a low level of oxidation even in the later stages of parasite development. Treatment with a pro-oxidant compound caused increased oxidation of the probe in the parasite compartment, but less so in the host cell membrane. Conversely, treatment with ferricyanide increases oxidation of the probe in the erythrocyte cell membrane but does not inhibit parasite growth. Chromatographic analysis of the lipids in infected erythrocytes shows no evidence for loss of a-tocopherol or the accumulation of lipid hydroperoxides indicating that, despite the increased oxidative stress, the parasite membranes remain protected from substantial lipid oxidation. We have established BODIPY 581/591-PC as a useful probe of the spatial distribution of oxidative stress in P. falciparum-infected erythrocytes; however, the probe appears to be more sensitive to oxidative damage than endogenous lipids. ' 2009 International Society for Advancement of Cytometry Key terms malaria; Plasmodium falciparum; oxidative stress; BODIPY 581/591-PC; lipid oxidation OXIDATIVE damage to protein and membrane components plays important roles in various diseases and in the aging process (1), and a number of methods have been developed for measuring oxidative stress in cellular systems. In some studies, the levels of oxidized lipids and proteins have been measured directly (2,3). In other studies, secondary reaction products, such as malondialdehyde, have been used as a surrogate measure of lipid oxidation (4). These approaches offer useful insights into oxidative events; however, they usually require physical disruption of the system under investigation.Recently, fluorescence-based probes of oxidative stress have gained popularity as relatively nonperturbing sensors of cellular stresses (5-7). The fatty acid (FA) analogue, cis-paranaric acid (8), has been used as an oxidant-sensitive fluorophore; however, its fluorescence in the UV range is a disadvantage in some applications. BODIPY 581/591 is an alternative probe that can be excited in the visible range and

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The Molecular Pathobiology of Cell Membrane Iron: The Sickle Red Cell as a Model

Cited by 85 publications

References 60 publications

Up-regulation of α1-microglobulin by hemoglobin and reactive oxygen species in hepatoma and blood cell lines

Up-regulation of α1-microglobulin by hemoglobin and reactive oxygen species in hepatoma and blood cell lines

Spectrin's E2/E3 ubiquitin conjugating/ligating activity is diminished in sickle cells

A phosphatidylcholine‐BODIPY 581/591 conjugate allows mapping of oxidative stress in P. falciparum‐infected erythrocytes

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