The effect of lipid oxidation on the water permeability of phospholipids bilayers

Lis, Mateusz; Wizert, Alicja; Przybyło, Magdalena; Langner, Marek; Świątek, Jerzy; Jungwirth, Pavel; Ćwiklik, Łukasz

doi:10.1039/c1cp21009b

Cited by 90 publications

(154 citation statements)

References 53 publications

Supporting

Mentioning

134

Contrasting

Order By: Relevance

“…Sensitization involves both impaired detoxification of lipid peroxides, due to reduced expression of GPX4, and generation of hydrogen peroxide, via NOX4. A major consequence of lipid peroxidation is loss of impermeability to water (Lis et al., 2011, Wong-Ekkabut et al., 2007), providing an explanation for the characteristic cell swelling and rupture we observe.…”

Section: Discussionmentioning

confidence: 99%

Oncogene-Selective Sensitivity to Synchronous Cell Death following Modulation of the Amino Acid Nutrient Cystine

et al. 2017

View full text Add to dashboard Cite

SummaryCancer cells reprogram their metabolism, altering both uptake and utilization of extracellular nutrients. We individually depleted amino acid nutrients from isogenic cells expressing commonly activated oncogenes to identify correspondences between nutrient supply and viability. In HME (human mammary epithelial) cells, deprivation of cystine led to increased cell death in cells expressing an activated epidermal growth factor receptor (EGFR) mutant. Cell death occurred via synchronous ferroptosis, with generation of reactive oxygen species (ROS). Hydrogen peroxide promoted cell death, as both catalase and inhibition of NADPH oxidase 4 (NOX4) blocked ferroptosis. Blockade of EGFR or mitogen-activated protein kinase (MAPK) signaling similarly protected cells from ferroptosis, whereas treatment of xenografts derived from EGFR mutant non-small-cell lung cancer (NSCLC) with a cystine-depleting enzyme inhibited tumor growth in mice. Collectively, our results identify a potentially exploitable sensitization of some EGFR/MAPK-driven tumors to ferroptosis following cystine depletion.

show abstract

Section: Discussionmentioning

confidence: 99%

Oncogene-Selective Sensitivity to Synchronous Cell Death following Modulation of the Amino Acid Nutrient Cystine

et al. 2017

View full text Add to dashboard Cite

show abstract

“…4 Permeability also increases by an order of magnitude as the concentration of oxidized lipids increases. 17,18 Moreover, permeability increases by two orders of magnitude when a pore spans the bilayer (Table 2). When the concentration of α-toc inside the bilayer increases, water permeability decreases and pore formation becomes inhibited (Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…4,11,15,16 This reversal causes major changes in bilayer properties such as increase of area per lipid, bilayer thinning, decrease of lipid tail order parameter, and increase in water permeability. 4,12,[15][16][17][18] Recently, we performed MD simulations of lipid bilayers with oxidized lipids at high concentrations. Two major oxidized lipid species including hydroperoxide and aldehyde were studied.…”

mentioning

confidence: 99%

Alpha-tocopherol inhibits pore formation in oxidized bilayers

Boonnoy

Karttunen

Wong-ekkabut

2017

Phys. Chem. Chem. Phys.

View full text Add to dashboard Cite

ABSTRACT:In biological membranes, alpha-tocopherols (α-toc; vitamin E) protect polyunsaturated lipids from free radicals. Although the interactions of α-toc with nonoxidized lipid bilayers have been studied, their on oxidized bilayers remain unknown. In this study, atomistic molecular dynamics (MD) simulations of oxidized lipid bilayers were performed with varying concentrations of α-toc. Bilayers with 1-palmitoyl-2-lauroyl-sn-glycero-3-phosphocholine (PLPC) lipids and its aldehyde derivatives at 1:1 ratio were studied. Our simulations show that oxidized lipids self-assemble into aggregates with a water pore rapidly developing across the lipid bilayer. The free energy of transporting an α-toc molecule in a lipid bilayer suggests that α-tocs can passively adsorb into the bilayer. When α-toc molecules were present at low concentrations in bilayers containing oxidized lipids, the formation of water pores was slowed down. At high α-toc concentrations, no pores were observed. Based on the simulations, we propose that the mechanism of how α-toc inhibits pore formation in bilayers with oxidized lipids is the following: α-tocs trap the polar groups of the oxidized lipids at the membrane-water interface resulting in a decreased probability for the oxidized lipids to reach contact with the two leaflets and initiate pore formation. This demonstrates that α-toc molecules not only protect the bilayer from oxidation but also help to stabilize the bilayer after lipid peroxidation occurs. These results will help in designing more efficient molecules to protect membranes from oxidative stress.Biological membranes serve as a partition between cells and their environment. Under oxidative stress, unsaturated lipids present in cell membranes may become exposed to attacks by free radicals, that is, oxidation. Oxidation transforms some of the membrane lipids to oxidized ones such as hydroperoxide and aldehyde lipids. 1,2It has also been suggested that internal, that is intra-leaflet, oxidation may be important in altering bilayer properties. 3Lipid peroxidation is an important mechanism of cell membrane damage. [4][5][6] Previous experiments and computer simulations 4,[7][8][9][10][11][12][13][14] have demonstrated how oxidized lipids disturb and deform bilayers. The polar chains in oxidized lipids are energetically unfavorable to stay in the bilayer's interior resulting in the reversal of the polar lipid chain to the bilayer interface. 4,11,15,16 This reversal causes major changes in bilayer properties such as increase of area per lipid, bilayer thinning, decrease of lipid tail order parameter, and increase in water permeability. 4,12,[15][16][17][18] Recently, we performed MD simulations of lipid bilayers with oxidized lipids at high concentrations. Two major oxidized lipid species including hydroperoxide and aldehyde were studied. The results showed that only aldehyde lipids were able to induce pore formation across a PLPC lipid bilayer and cause significant bilayer deformation. 13,15α-toc is well-known as an efficient antioxidant ...

show abstract

“…The reorientation of the sn-2 tail of POVPC results in a mean tilt angle of 73 with a standard deviation of 23 , corresponding to a high probability of the oxidized tail assuming orientations that are nearly perpendicular to the bilayer normal and parallel to the lipid/water interface. There is, however, some overlap between the sn-2 angle distributions of POPC and POVPC, indicating a small probability for POVPC to assume some of the usual sn-2 tail orientations.…”

Section: Simulation Resultsmentioning

confidence: 99%

“…This provides a potential for increased water penetration mediated by well-hydrated polar and anionic moieties moving between the aqueous interface and the membrane core. We thus provide a possible mechanistic basis for the increase in water penetration that has reportedly accompanied bilayer incorporation of several types of oxidized lipids (22,(72)(73)(74)(75).…”

Section: Comparative Analysis Of Pgpc and Povpc: Computational Studiesmentioning

confidence: 99%

Molecular-Scale Biophysical Modulation of an Endothelial Membrane by Oxidized Phospholipids

Ayee

LeMaster

Shentu

et al. 2017

Biophysical Journal

View full text Add to dashboard Cite

The influence of two bioactive oxidized phospholipids on model bilayer properties, membrane packing, and endothelial cell biomechanics was investigated computationally and experimentally. The truncated tail phospholipids, 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) and 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC), are two major oxidation products of the unsaturated phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycero-phosphocholine. A combination of coarse-grained molecular dynamics simulations, Laurdan multiphoton imaging, and atomic force microscopy microindentation experiments was used to determine the impact of POVPC and PGPC on the structure of a multicomponent phospholipid bilayer and to assess the consequences of their incorporation on membrane packing and endothelial cell stiffness. Molecular simulations predicted differential bilayer perturbation effects of the two oxidized phospholipids based on the chemical identities of their truncated tails, including decreased bilayer packing, decreased bilayer bending modulus, and increased water penetration. Disruption of lipid order was consistent with Laurdan imaging results indicating that POVPC and PGPC decrease the lipid packing of both ordered and disordered membrane domains. Computational predictions of a larger membrane perturbation effect by PGPC correspond to greater stiffness of PGPC-treated endothelial cells observed by measuring cellular elastic moduli using atomic force microscopy. Our results suggest that disruptions in membrane structure by oxidized phospholipids play a role in the regulation of overall endothelial cell stiffness.

show abstract

The effect of lipid oxidation on the water permeability of phospholipids bilayers

Cited by 90 publications

References 53 publications

Oncogene-Selective Sensitivity to Synchronous Cell Death following Modulation of the Amino Acid Nutrient Cystine

Oncogene-Selective Sensitivity to Synchronous Cell Death following Modulation of the Amino Acid Nutrient Cystine

Alpha-tocopherol inhibits pore formation in oxidized bilayers

Molecular-Scale Biophysical Modulation of an Endothelial Membrane by Oxidized Phospholipids

Contact Info

Product

Resources

About