Effect of Sterols on β-Amyloid Peptide (AβP 1–40) Channel Formation and their Properties in Planar Lipid Membranes

Micelli, S.; Meleleo, Daniela; Picciarelli, V.; Gallucci, E.

doi:10.1016/s0006-3495(04)74281-2

Cited by 72 publications

(76 citation statements)

References 39 publications

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“…Thus, it would seem that digitoxin channels are more like the classical channel former alamethacin, which assembles as a multimeric ''barrel stave'' structure for which the ion selectivity is independent of phospholipid composition (24,25). Many other types of sterols are altogether electrically silent (27), further supporting the structural specificity of the digitoxin channel.…”

Section: Discussionmentioning

confidence: 97%

Heart failure drug digitoxin induces calcium uptake into cells by forming transmembrane calcium channels

Arispe

Díaz

Šimáková

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Digitoxin and other cardiac glycosides are important, centuries-old drugs for treating congestive heart failure. However, the mechanism of action of these compounds is still being elucidated. Calcium is known to potentiate the toxicity of these drugs, and we have hypothesized that digitoxin might mediate calcium entry into cells. We report here that digitoxin molecules mediate calcium entry into intact cells. Multimers of digitoxin molecules also are able to form calcium channels in pure planar phospholipid bilayers. These digitoxin channels are blocked by Al 3؉ and La 3؉ but not by Mg 2؉ or the classical L-type calcium channel blocker, nitrendipine. In bilayers, we find that the chemistry of the lipid affects the kinetics of the digitoxin channel activity, but not the cation selectivity. Antibodies against digitoxin promptly neutralize digitoxin channels in both cells and bilayers. We propose that these digitoxin calcium channels may be part of the mechanism by which digitoxin and other active cardiac glycosides, such as digoxin, exert system-wide actions at and above the therapeutic concentration range.cardiac glycoside ͉ cytotoxicity

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Section: Discussionmentioning

confidence: 97%

Heart failure drug digitoxin induces calcium uptake into cells by forming transmembrane calcium channels

Arispe

Díaz

Šimáková

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…PLMs made up of DOPS:DOPE:POPC (27:27:18, w:w:w) in 1% n-decane (Fluka) were formed as previously described [18,22]. The channel current was monitored in different salt solutions, i.e.…”

Section: Single Channel Measurementmentioning

confidence: 99%

Studies on the Effect of Salts on the Channel Activity of Kissper, a Kiwi Fruit Peptide

Meleleo¹

2012

TONUTRAJ

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Fruits and vegetables are known to possess health benefits: indeed, they contain a large number of bioactive molecules with a positive impact on human health. Dietary proteins possess specific biological properties which make these components potential ingredients of functional or health-promoting foods. Many of these properties are attributed to physiologically-active peptides encrypted in protein molecules.Kissper, a 39-residue peptide isolated from kiwi fruit (Actinidia deliciosa), derives from the processing of kiwellin, a well-represented novel allergenic protein present in the edible part of the fruit. Kissper has six cysteine residues forming three disulfide bridges. This cysteine pattern is similar, but not identical, to those observed in some plant and animal proteins, including toxins involved in defence mechanisms. We show that kissper forms ion channels in DOPS:DOPE:POPC PLMs in different media, such as KCl, potassium gluconate, potassium citrate and potassium phosphate monobasic. Kissper's channels show a strong voltage dependence in all media used, and an estimated pore diameter in the range from 1.9 to 7.6 Å in KCl medium. Finally, kissper's pores shift selectivity from anions to neutral to cations, depending on the nature of the salt solutions. Therefore we propose the kissper as a novel nutraceutical component of kiwi fruit that may have a positive impact on human health due to its channel-like pathways which modulate membrane permeability. The kissper action might promote the adsorption of substances, in particular, within the gastrointestinal tract, helping digestion, preventing constipation and harmful accumulation of metabolites.

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“…Micelli et al (2004) had prepared three different compositions of two-component model membranes in order to investigate the effect of membrane composition on the interaction and self-assembly of the Ab peptide during pore formation in planar lipid membranes. Of further interest was the observation that the incorporation/insertion of the Ab-peptide into the membrane was not only influenced by membrane structure but also the surface potential of the membrane.…”

Section: Lipid Modulation Of Amyloid Beta Aggregation and Neurotoxicitymentioning

confidence: 99%

Using model membranes for the study of amyloid beta:lipid interactions and neurotoxicity

Vestergaard

Hamada

Takagi

2008

Biotech & Bioengineering

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One of the major tasks in understanding the etiopathogenesis of amyloid beta-induced neurotoxicity of Alzheimer's disease (AD), is in fully capturing the large number of the biochemical processes that influence each other during the course of the disease, in vivo. Model membranes possess, as their main strength, the ability to enable the researcher to manipulate a 'biological' microvesicle under a controlled environment. This review narrowly focuses on discussing the exploitation of model membranes for improved understanding of some of the mechanisms governing AD's amyloid beta-induced neurotoxicity. Amyloid beta (Ab) is cleaved from a membranelocated amyloid precursor protein by membrane-located enzymes. The relative spatial localization of the involved biomolecules within the membrane bilayer is crucial in influencing Ab production, its aggregation on the membrane surface or insertion into the membrane, and fibril formation: all important processes in causing neurotoxicity. The lipid composition of the bilayer is similarly important. The review also attempts to highlight current and future challenges in using model membranes for studying biochemical processes.

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Effect of Sterols on β-Amyloid Peptide (AβP 1–40) Channel Formation and their Properties in Planar Lipid Membranes

Cited by 72 publications

References 39 publications

Heart failure drug digitoxin induces calcium uptake into cells by forming transmembrane calcium channels

Heart failure drug digitoxin induces calcium uptake into cells by forming transmembrane calcium channels

Studies on the Effect of Salts on the Channel Activity of Kissper, a Kiwi Fruit Peptide

Using model membranes for the study of amyloid beta:lipid interactions and neurotoxicity

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