Plasma Membrane Phospholipid Asymmetry

Quinn, Peter J.

doi:10.1007/0-306-47931-1_3

Cited by 59 publications

(38 citation statements)

References 87 publications

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“…The phospholipid component is normally found on the internal/cytosolic side of the membrane in healthy cells. This protein translocation is key for the detection of apoptosis by annexin V. 47 In late stages of apoptosis, the membrane is totally compromised as the cell breaks apart into several vesicles or apoptotic bodies. In the process, membrane blebbing allows formerly impermeant agents, like propidium iodide (PI), to access inner cell compartments.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

The Contrasting Activity of Iodido versus Chlorido Ruthenium and Osmium Arene Azo- and Imino-pyridine Anticancer Complexes: Control of Cell Selectivity, Cross-Resistance, p53 Dependence, and Apoptosis Pathway

2013

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activity of iodido versus chlorido ruthenium and osmium arene azo-and imino-pyridine anticancer complexes : control of cell selectivity, cross-resistance, p53 dependence, and apoptosis pathway. Journal of Medicinal Chemistry, Vol.56 (No.3). pp. 1291-1300. Permanent WRAP url: http://wrap.warwick.ac.uk/53124 Copyright and reuse:The Warwick Research Archive Portal (WRAP) makes the work of researchers of the University of Warwick available open access under the following conditions. Copyright © and all moral rights to the version of the paper presented here belong to the individual author(s) and/or other copyright owners. To the extent reasonable and practicable the material made available in WRAP has been checked for eligibility before being made available.Copies of full items can be used for personal research or study, educational, or not-forprofit purposes without prior permission or charge. Provided that the authors, title and full bibliographic details are credited, a hyperlink and/or URL is given for the original metadata page and the content is not changed in any way. and X  Cl or I, exhibit potent antiproliferative activity toward a range of cancer cells. Not only are the iodido complexes more potent than the chlorido analogues, but they are not crossresistant with the clinical platinum drugs cisplatin and oxaliplatin. They are also more selective for cancer cells versus normal cells (fibroblasts) and show high accumulation in cell membranes. They arrest cell growth in G1 phase in contrast to cisplatin (S phase) with a high incidence of late-stage apoptosis. The iodido complexes retain potency in p53 mutant colon cells. All complexes activate caspase 3. In general, antiproliferative activity is greatly enhanced by low levels of the glutathione synthase inhibitor L-buthionine sulfoxime. The work illustrates how subtle changes to the design of low-spin d 6 metal complexes can lead to major changes in cellular metabolism and to potent complexes with novel mechanisms of anticancer activity. Publisher

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Section: ■ Results and Discussionmentioning

confidence: 99%

The Contrasting Activity of Iodido versus Chlorido Ruthenium and Osmium Arene Azo- and Imino-pyridine Anticancer Complexes: Control of Cell Selectivity, Cross-Resistance, p53 Dependence, and Apoptosis Pathway

2013

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“…The idea that the plasma membrane is relevant in neural transmission is very plausible for the following reason: it has domains with negative charges due to the prevalence of anionic phospholipids [32,33,34] that regulate diverse physiological processes through electrostatic interactions [33,35,36,37,38,39,40], in which the phosphatidic acid plays an important role in the signalling events [41].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Calcium and protons affect the interaction of neurotransmitters and anesthetics with anionic lipid membranes

Pérez-Isidoro¹,

Ruiz‐Suárez²

2016

Biochimica et Biophysica Acta (BBA) - Biomembranes

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We study how zwitterionic and anionic biomembrane models interact with neurotransmitters (NTs) and anesthetics (ATs) in the presence of Ca(2+) and different pH conditions. As NTs we used acetylcholine (ACh), γ-aminobutyric acid (GABA), and l-glutamic acid (LGlu). As ATs, tetracaine (TC), and pentobarbital (PB) were employed. By using differential scanning calorimetry (DSC), we analyzed the changes such molecules produce in the thermal properties of the membranes. We found that calcium and pH play important roles in the interactions of NTs and ATs with the anionic lipid membranes. Changes in pH promote deprotonation of the phosphate groups in anionic phospholipids inducing electrostatic interactions between them and NTs; but if Ca(2+) ions are in the system, these act as bridges. Such interactions impact the physical properties of the membranes in a similar manner that anesthetics do. Beyond the usual biochemical approach, we claim that these effects should be taken into account to understand the excitatory-inhibitory orchestrated balance in the nervous system.

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“…In particular, the outer leaflet of the plasma membrane is rich in phosphatidylcholine and sphingolipids, while the leaflet facing the cytoplasm is rich in phosphatidylethanolamine, phosphatidylserine and other, mostly anionic, phospholipids [82]. An asymmetry in the unsaturation of their fatty-acyl chains runs parallel: the lipids enriched in the outer surface have an abundance of saturated chains, while the inner surface species are characteristically poly-unsaturated [83].…”

Section: Cholesterol Activity In the Two Bilayer Leafletsmentioning

confidence: 99%

Cholesterol homeostasis and the escape tendency (activity) of plasma membrane cholesterol

Lange

Steck

2008

Progress in Lipid Research

143

192

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We review evidence that sterols can form stoichiometric complexes with certain bilayer phospholipids, and sphingomyelin in particular. These complexes appear to be the basis for the formation of condensed and ordered liquid phases, (micro)domains and/or rafts in both artificial and biological membranes. The sterol content of a membrane can exceed the complexing capacity of its phospholipids. The excess, uncomplexed membrane sterol molecules have a relatively high escape tendency, also referred to as fugacity or chemical activity (and, here, simply activity). Cholesterol is also activated when certain membrane intercalating amphipaths displace it from the phospholipid complexes. Active cholesterol projects from the bilayer and is therefore highly susceptible to attack by cholesterol oxidase. Similarly, active cholesterol rapidly exits the plasma membrane to extracellular acceptors such as cyclodextrin and high-density lipoproteins. For the same reason, the pool of cholesterol in the ER (endoplasmic reticulum) increases sharply when cell surface cholesterol is incremented above the physiological set-point; i.e., equivalence with the complexing phospholipids. As a result, the escape tendency of the excess cholesterol not only returns the plasma membrane bilayer to its set point but also serves as a feedback signal to intracellular homeostatic elements to down-regulate cholesterol accretion.

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Plasma Membrane Phospholipid Asymmetry

Cited by 59 publications

References 87 publications

The Contrasting Activity of Iodido versus Chlorido Ruthenium and Osmium Arene Azo- and Imino-pyridine Anticancer Complexes: Control of Cell Selectivity, Cross-Resistance, p53 Dependence, and Apoptosis Pathway

The Contrasting Activity of Iodido versus Chlorido Ruthenium and Osmium Arene Azo- and Imino-pyridine Anticancer Complexes: Control of Cell Selectivity, Cross-Resistance, p53 Dependence, and Apoptosis Pathway

Calcium and protons affect the interaction of neurotransmitters and anesthetics with anionic lipid membranes

Cholesterol homeostasis and the escape tendency (activity) of plasma membrane cholesterol

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