H1 helix of colicin U causes phospholipid membrane permeation

2022 ◽  
pp. 183866
Author(s):  
Kamila Riedlová ◽  
Tereza Dolejšová ◽  
Radovan Fišer ◽  
Lukasz Cwiklik
Keyword(s):  
Membrane Permeation ◽  
Phospholipid Membrane

scholarly journals Evaluation of the correlation between porphyrin accumulation in cancer cells and functional positions for application as a drug carrier

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Koshi Nishida ◽  
Toshifumi Tojo ◽  
Takeshi Kondo ◽  
Makoto Yuasa
Keyword(s):  
Cancer Cells ◽  
Drug Carrier ◽  
Bilayer Membrane ◽  
Phospholipid Bilayer ◽  
Membrane Permeation ◽  
Porphyrin Derivatives ◽  
Phospholipid Bilayer Membrane ◽  
Meso Position ◽  
Tumor Accumulation ◽  
Binding Position

AbstractPorphyrin derivatives accumulate selectively in cancer cells and are can be used as carriers of drugs. Until now, the substituents that bind to porphyrins (mainly at the meso-position) have been actively investigated, but the effect of the functional porphyrin positions (β-, meso-position) on tumor accumulation has not been investigated. Therefore, we investigated the correlation between the functional position of substituents and the accumulation of porphyrins in cancer cells using cancer cells. We found that the meso-derivative showed higher accumulation in cancer cells than the β-derivative, and porphyrins with less bulky substituent actively accumulate in cancer cells. When evaluating the intracellular distribution of porphyrin, we found that porphyrin was internalized by endocytosis and direct membrane permeation. As factors involved in these two permeation mechanisms, we evaluated the affinity between porphyrin-protein (endocytosis) and the permeability to the phospholipid bilayer membrane (direct membrane permeation). We found that the binding position of porphyrin affects the factors involved in the transmembrane permeation mechanisms and impacts the accumulation in cancer cells.

scholarly journals Phospholipase A2 inhibitor–loaded micellar nanoparticles attenuate inflammation and mitigate osteoarthritis progression

2021 ◽  
Vol 7 (15) ◽  
pp. eabe6374
Author(s):  
Yulong Wei ◽  
Lesan Yan ◽  
Lijun Luo ◽  
Tao Gui ◽  
Biang Jang ◽  
...  
Keyword(s):  
Clinical Success ◽  
Joint Space ◽  
Therapeutic Agents ◽  
Knee Joints ◽  
Phospholipid Membrane ◽  
Drug Discovery And Development ◽  
Knee Oa ◽  
Clinical Challenge ◽  
Osteoarthritis Progression ◽  
Human And Mouse

Treating osteoarthritis (OA) remains a major clinical challenge. Despite recent advances in drug discovery and development, no disease-modifying drug for knee OA has emerged with any notable clinical success, in part, due to the lack of valid and responsive therapeutic targets and poor drug delivery within knee joints. In this work, we show that the amount of secretory phospholipase A2 (sPLA2) enzyme increases in the articular cartilage in human and mouse OA cartilage tissues. We hypothesize that the inhibition of sPLA2 activity may be an effective treatment strategy for OA. To develop an sPLA2-responsive and nanoparticle (NP)–based interventional platform for OA management, we incorporated an sPLA2 inhibitor (sPLA2i) into the phospholipid membrane of micelles. The engineered sPLA2i-loaded micellar NPs (sPLA2i-NPs) were able to penetrate deep into the cartilage matrix, prolong retention in the joint space, and mitigate OA progression. These findings suggest that sPLA2i-NPs can be promising therapeutic agents for OA treatment.

scholarly journals Phospholipid Membrane Formation Templated by Coacervate Droplets

Langmuir ◽  
2021 ◽  
Author(s):  
Fatma Pir Cakmak ◽  
Allyson M. Marianelli ◽  
Christine D. Keating
Keyword(s):  
Phospholipid Membrane ◽  
Membrane Formation

scholarly journals A Synergic Potential of Antimicrobial Peptides against Pseudomonas syringae pv. actinidiae

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1461
Author(s):  
Nuno Mariz-Ponte ◽  
Laura Regalado ◽  
Emil Gimranov ◽  
Natália Tassi ◽  
Luísa Moura ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Antimicrobial Peptides ◽  
Pseudomonas Syringae ◽  
Pathogenic Bacteria ◽  
High Efficiency ◽  
Bacterial Canker ◽  
Membrane Permeation ◽  
Flow Cytometry Analysis ◽  
Pathogenic Agent ◽  
Peptide Mixtures

Pseudomonas syringae pv. actinidiae (Psa) is the pathogenic agent responsible for the bacterial canker of kiwifruit (BCK) leading to major losses in kiwifruit productions. No effective treatments and measures have yet been found to control this disease. Despite antimicrobial peptides (AMPs) having been successfully used for the control of several pathogenic bacteria, few studies have focused on the use of AMPs against Psa. In this study, the potential of six AMPs (BP100, RW-BP100, CA-M, 3.1, D4E1, and Dhvar-5) to control Psa was investigated. The minimal inhibitory and bactericidal concentrations (MIC and MBC) were determined and membrane damaging capacity was evaluated by flow cytometry analysis. Among the tested AMPs, the higher inhibitory and bactericidal capacity was observed for BP100 and CA-M with MIC of 3.4 and 3.4–6.2 µM, respectively and MBC 3.4–10 µM for both. Flow cytometry assays suggested a faster membrane permeation for peptide 3.1, in comparison with the other AMPs studied. Peptide mixtures were also tested, disclosing the high efficiency of BP100:3.1 at low concentration to reduce Psa viability. These results highlight the potential interest of AMP mixtures against Psa, and 3.1 as an antimicrobial molecule that can improve other treatments in synergic action.

scholarly journals Analysis of extracellular vesicle mRNA derived from plasma using the nCounter platform

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jillian W. P. Bracht ◽  
Ana Gimenez-Capitan ◽  
Chung-Ying Huang ◽  
Nicolas Potie ◽  
Carlos Pedraz-Valdunciel ◽  
...  
Keyword(s):  
Genomic Dna ◽  
Rna Extraction ◽  
Membrane Vesicles ◽  
Gene Signature ◽  
Extracellular Vesicle ◽  
Probe Design ◽  
Phospholipid Membrane ◽  
Lower Plasma ◽  
Mrna Targets ◽  
Dnase Treatment

AbstractExtracellular vesicles (EVs) are double-layered phospholipid membrane vesicles that are released by most cells and can mediate intercellular communication through their RNA cargo. In this study, we tested if the NanoString nCounter platform can be used for the analysis of EV-mRNA. We developed and optimized a methodology for EV enrichment, EV-RNA extraction and nCounter analysis. Then, we demonstrated the validity of our workflow by analyzing EV-RNA profiles from the plasma of 19 cancer patients and 10 controls and developing a gene signature to differentiate cancer versus control samples. TRI reagent outperformed automated RNA extraction and, although lower plasma input is feasible, 500 μL provided highest total counts and number of transcripts detected. A 10-cycle pre-amplification followed by DNase treatment yielded reproducible mRNA target detection. However, appropriate probe design to prevent genomic DNA binding is preferred. A gene signature, created using a bioinformatic algorithm, was able to distinguish between control and cancer EV-mRNA profiles with an area under the ROC curve of 0.99. Hence, the nCounter platform can be used to detect mRNA targets and develop gene signatures from plasma-derived EVs.

The Orientation of Cytochrome c Oxidase in Coupled Phospholipid Membrane Vesicles—A Spin-Label Study

1975 ◽  
Vol 53 (3) ◽  
pp. 364-370 ◽  
Author(s):  
J. A. Kornblatt ◽  
W. L. Chen ◽  
J. C. Hsia ◽  
G. R. Williams
Keyword(s):  
Molecular Weight ◽  
Binding Site ◽  
Cytochrome Oxidase ◽  
Spin Label ◽  
Resonance Spectrum ◽  
Membrane Vesicles ◽  
Phospholipid Membrane ◽  
Vesicle Membrane ◽  
Exterior Surface ◽  
Label Study

Cytochrome oxidase, an enzyme containing six different subunits, has been shown to span the inner mitochrondrial membrane. The arrangement of the subunits within the membrane is unknown. We have specifically labeled the 25 000 molecular weight subunit with a spin-label derivative of N-ethylmaleimide, 3-maleimido-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl (NEM-SL(5)). NEM-SL(5)-labeled cytochrome oxidase can be incorporated into phospholipid membranes to form coupled vesicles of the Hinkle, Kim &Racker ((1972) J. Biol. Chem. 247, 1338–1339) type. The resonance spectrum of NEM-SL(5) is similar in both soluble and vesicular cytochrome oxidase. Since ascorbate has been shown to reduce only spin label that is exposed to the exterior surface of a closed vesicle, we have used ascorbate to determine the NEM-SL(5)-binding site in the coupled vesicles. NEM-SL(5)-labeled cytochrome oxidase vesicles are reduced by 10 mM ascorbate with [Formula: see text] of 1 min at 22 °C. The rate of reduction is relatively independent of temperature. We conclude that (1) cytochrome oxidase is unidirectionally or preferentially oriented in the vesicle membrane, and (2) the NEM-SL(5)-binding site on the 25 000 molecular weight subunit is exposed to the external aqueous medium.

scholarly journals Familial Parkinson's Disease Mutant E46K α-Synuclein Localizes to Membranous Structures, Forms Aggregates, and Induces Toxicity in Yeast Models

2011 ◽  
Vol 2011 ◽  
pp. 1-14 ◽  
Author(s):  
Michael Fiske ◽  
Michael White ◽  
Stephanie Valtierra ◽  
Sara Herrera ◽  
Keith Solvang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Plasma Membrane ◽  
Mutant Form ◽  
Phospholipid Membrane ◽  
Endomembrane System ◽  
Wild Type ◽  
Significant Toxicity ◽  
Familial Parkinson’S Disease

In Parkinson’s disease (PD), midbrain dopaminergic neuronal death is linked to the accumulation of aggregated α-synuclein. The familial PD mutant form of α-synuclein, E46K, has not been thoroughly evaluated yet in an organismal model system. Here, we report that E46K resembled wild-type (WT) α-synuclein in Saccharomyces cerevisiae in that it predominantly localized to the plasma membrane, and it did not induce significant toxicity or accumulation. In contrast, in Schizosaccharomyces pombe, E46K did not associate with the plasma membrane. Instead, in one strain, it extensively aggregated in the cytoplasm and was as toxic as WT. Remarkably, in another strain, E46K extensively associated with the endomembrane system and was more toxic than WT. Our studies recapitulate and extend aggregation and phospholipid membrane association properties of E46K previously observed in vitro and cell culture. Furthermore, it supports the notion that E46K generates toxicity partly due to increased association with endomembrane systems within cells.

scholarly journals Study on cholesterol distribution in a phospholipid membrane : II

2000 ◽  
Vol 40 (supplement) ◽  
pp. S85
Author(s):  
T. Adachi ◽  
M. Furusaka ◽  
T. Otomo ◽  
I. Hatta
Keyword(s):  
Phospholipid Membrane
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