Alzheimer amyloid β‐peptides exhibit ionophore‐like properties in human erythrocytes

Engström, Iva; Ronquist, Gunnar; Pettersson, Linnéa; Waldenström, Anders

doi:10.1111/j.1365-2362.1995.tb01732.x

Cited by 60 publications

(48 citation statements)

References 32 publications

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“…Amyloid peptides may affect function and integrity of erythrocytes [23][24][25][26][27][28][29][30][31][32]. Whether or not amyloid peptides trigger suicidal death of erythrocytes, however, remained elusive.…”

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confidence: 99%

Amyloid Induced Suicidal Erythrocyte Death

Nicolay

Gatz

Liebig

et al. 2007

Cell Physiol Biochem

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Amyloid peptides are known to induce apoptosis in a wide variety of cells. Erythrocytes may similarly undergo suicidal death or eryptosis, which is characterized by scrambling of the cell membrane with subsequent exposure of phosphatidylserine (PS) at the cell surface. Eryptosis is triggered by increase of cytosolic Ca²⁺ activity and by activation of acid sphingomyelinase with subsequent formation of ceramide. Triggers of eryptosis include energy depletion and isosmotic cell shrinkage (replacement of extracellular Cl^- by impermeable gluconate for 24 h). The present study explored whether amyloid peptide Aβ _1-42 could trigger eryptosis and to possibly identify underlying mechanisms. Erythrocytes from healthy volunteers were exposed to amyloid and PS-exposure (annexin V binding), cell volume (forward scatter), cytosolic Ca²⁺ activity (Fluo3 fluorescence) and ceramide formation (anti-ceramide antibody) were determined by FACS analysis. Exposure of erythrocytes to the amyloid peptide Aβ _1-42 (? 0.5 µM) for 24 h significantly triggered annexin V binding, an effect mimicked to a lesser extent by the amyloid peptide Aβ _1-40 (1 µM). Aβ _1-42 (? 1.0 µM) further significantly decreased forward scatter of erythrocytes. The effect of Aβ _1-42 (? 0.5 µM) on erythrocyte annexin V binding was paralleled by formation of ceramide but not by significant increase of cytosolic Ca²⁺ activity. The presence of Aβ _1-42 further significantly enhanced the eryptosis following Cl^- depletion but not of glucose depletion for 24 hours. The present observations disclose a novel action of Aβ _1-42, which may well contribute to the pathophysiological effects of amyloid peptides, such as vascular complications in Alzheimer''s disease.

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Section: +mentioning

confidence: 99%

Amyloid Induced Suicidal Erythrocyte Death

Nicolay

Gatz

Liebig

et al. 2007

Cell Physiol Biochem

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“…Nonphysiologic fragments of A␤ such as A␤25-35 have been demonstrated to possess many of the cytotoxic, amyloidogenic, and membrane-disrupting properties of fulllength A␤ (20,21). Other studies demonstrate that A␤ exhibits ionophore-like activity to induce calcium influx into erythrocytes (22), neurons (23), and neuron-like cells (24).…”

Section: Introductionmentioning

confidence: 99%

Alzheimer amyloid aβ1-42 channels: Effects of solvent, pH, and congo red

1999

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Substantial genetic and biochemical evidence implicates amyloid peptides (Abeta) in the etiology of Alzheimer's Disease (AD). Recent evidence indicates that Abeta1-42 is the predominant species in the hallmark senile amyloid plaque of AD. Furthermore, Abeta1-42 forms aggregates inside lysosomes of cultured neurons leading to lysosomal disruption and cell death. We report here that Abeta1-42 forms slightly cation selective, voltage-independent ion channels with multiple conductance levels at neurotoxic concentrations in planar bilayer membranes. The channels show substantial irregularity of activity, and the size of conductances and the length of open lifetimes depend on solvent history. Formation of channels requires anionic lipids, is enhanced in acidic solutions, and is inhibited by Congo Red. These properties suggest that the channels are formed by aggregates of Abeta1-42. In addition, the channels are reversibly blocked by zinc in a voltage-independent manner. The properties of these channels would likely render them neurotoxic to relevant neurons in vivo. These results are consistent with the channel hypothesis of Abeta neurotoxicity.

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“…Also accumulation of Aβ(1-42) can induce neurotoxicity by binding to the nicotinic acetylcholine receptor (Wang et al, 2000), forming calcium and potassium channels in cell membranes (Arispe et al, 1993;Etcheberrigaray et al, 1994;Engstrom et al, 1995), decreasing glucose transport across brain endothelial cells (Blanc et al, 1997), and actuating the release of chemokines (Fiala et al, 1998) and cytokines (Akama and Van Eldik, 2000).…”

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confidence: 99%