scholarly journals Interactions of the Lysosomotropic Detergent O-Methyl-Serine Dodecylamide Hydrochloride (MSDH) with Lipid Bilayer Membranes—Implications for Cell Toxicity

2020 ◽  
Vol 21 (9) ◽  
pp. 3136 ◽  
Author(s):  
Ana-Maria Villamil Giraldo ◽  
Ida Eriksson ◽  
Stefan Wennmalm ◽  
Timmy Fyrner ◽  
Thomas Ederth ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Membrane Lipids ◽  
Apoptotic Cell ◽  
Human Fibroblasts ◽  
Membrane Integrity ◽  
Chemical Properties ◽  
High Ratio ◽  
Lipid Bilayer Membranes ◽  
High Concentration ◽  
Liposome Membrane

O-methyl-serine dodecylamine hydrochloride (MSDH) is a detergent that accumulates selectively in lysosomes, a so-called lysosomotropic detergent, with unexpected chemical properties. At physiological pH, it spontaneously forms vesicles, which disassemble into small aggregates (probably micelles) below pH 6.4. In this study, we characterize the interaction between MSDH and liposomes at different pH and correlate the findings to toxicity in human fibroblasts. We find that the effect of MSDH on lipid membranes is highly pH-dependent. At neutral pH, the partitioning of MSDH into the liposome membrane is immediate and causes the leakage of small fluorophores, unless the ratio between MSDH and lipids is kept low. At pH 5, the partitioning of MSDH into the membrane is kinetically impeded since MSDH is charged and a high ratio between MSDH and the lipids is required to permeabilize the membrane. When transferred to cell culture conditions, the ratio between MSDH and plasma membrane lipids must therefore be low, at physiological pH, to maintain plasma membrane integrity. Transmission electron microscopy suggests that MSDH vesicles are taken up by endocytosis. As the pH of the endosomal compartment progressively drops, MSDH vesicles disassemble, leading to a high concentration of increasingly charged MSDH in small aggregates inside the lysosomes. At sufficiently high MSDH concentrations, the lysosome is permeabilized, the proteolytic content released to the cytosol and apoptotic cell death is induced.

Effects of Neutral Shampoos on Cultures of Human Fibroblasts

1991 ◽  
Vol 19 (1) ◽  
pp. 87-93
Author(s):  
Teresa Cavalletti ◽  
Eva Reali ◽  
Claudia Marangoni ◽  
Stefano Bader ◽  
Serena Traniello
Keyword(s):  
Plasma Membrane ◽  
Human Fibroblasts ◽  
Membrane Integrity ◽  
Neutral Red ◽  
Lactate Dehydrogenase Release ◽  
Fibroblast Cultures ◽  
Cellular Target ◽  
Red Dye ◽  
New Compounds

Criteria used to predict the effect of neutral shampoos on fibroblast cultures were based on assays which were easy to perform, reproducible and adaptable to a large number of substances. The tests were based on the determination of the integrity of the plasma membrane, the rate of protein synthesis, and cell viability. Six different shampoos were tested: four were of the best quality commercially available, while the other two were new compounds. The substances were tested over a wide concentration range and were applied to human fibroblast cultures for various exposure times. Lactate dehydrogenase release into the medium was used as a marker of plasma membrane integrity, the amount of [3H]-labelled protein in the fibroblasts was measured to assess the function of the cell biosynthetic machinery, and the number of damaged cells which did not take up the neutral red dye showed the percentage of cytolysis. The results indicated significant differences between the six shampoos, and a relationship between the biochemical parameters was found. This suggests that these tests on cell functionality may represent reliable markers for monitoring the cellular target damaged by xenobiotic compounds.

Adaptive Responses to the Stress Induced by Hyperthermia or Hydrogen Peroxide in Human Fibroblasts

2003 ◽  
Vol 228 (5) ◽  
pp. 491-498 ◽  
Author(s):  
S. Grasso ◽  
C. Scifo ◽  
V. Cardile ◽  
R. Gulino ◽  
M. Renis
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Ischemia Reperfusion Injury ◽  
Apoptotic Cell ◽  
Ischemia Reperfusion ◽  
Human Fibroblasts ◽  
Membrane Integrity ◽  
Adaptive Responses ◽  
Mitochondrial Potential ◽  
Cell Membrane Integrity

Perturbation of oxidant/antioxidant cellular balance, induced by cellular metabolism and by exogenous sources, causes deleterious effects to proteins, lipids, and nucleic acids, leading to a condition named “oxidative stress” that is involved in several diseases, such as cancer, ischemia-reperfusion injury, and neurodegenerative disorders. Among the exogenous agents, both H2O2 and hyperthermia have been implicated in oxidative stress promotion linked with the activation of apoptotic or necrotic mechanisms of cell death. The goal of this work was to better understand the involvement of some stress-related proteins in adaptive responses mounted by human fibroblasts versus the oxidative stress differently induced by 42°C hyperthermia or H2O2. The research was developed, switching off inducible nitric oxide synthase (iNOS) expression through antisense oligonucleotide transfection by studying the possible coregulation in the expression of HSP32 (also named HO-1), HSP70, and iNOS and their involvement in the induction of DNA damage. Several biochemical parameters, such as cell viability (MTT assay), cell membrane integrity (lactate dehydrogenase release), reactive oxygen species formation, glutathione levels, immunocytochemistry analysis of iNOS, HSP70, and HO-1 levels, genomic DNA fragmentation (HALO/COMET assay), and transmembrane mitochondrial potential (ΔΨ) were examined. Cells were collected immediately at the end of the stress-inducing treatment. The results, confirming the pleiotropic function of i-NOS, indicate that: (i) HO-1/HSP32, HSP70, and iNOS are finely tuned in their expression to contribute all together, in human fibroblasts, in ameliorating the resistance to oxidative stress damage; (ii) ROS exposure, at least in hyperthermia, in human fibroblasts contributes to growth arrest more than to apoptosis activation; and (iii) mitochondrial dysfunction, in presence of iNOS inhibition seems to be clearly involved in apoptotic cell death of human fibroblasts after H2O2 treatment, but not after hyperthermia.

scholarly journals Ultrastructural Alterations of Erwinia carotovora subsp. atroseptica Caused by Treatment with Aluminum Chloride and Sodium Metabisulfite

2004 ◽  
Vol 70 (11) ◽  
pp. 6800-6808 ◽  
Author(s):  
Elian-Simplice Yaganza ◽  
Danny Rioux ◽  
Marie Simard ◽  
Joseph Arul ◽  
Russell J. Tweddell
Keyword(s):  
Plasma Membrane ◽  
Aluminum Chloride ◽  
Prolonged Exposure ◽  
Membrane Damage ◽  
Membrane Integrity ◽  
Erwinia Carotovora ◽  
Cellular Membrane ◽  
Ultrastructural Changes ◽  
Sodium Metabisulfite ◽  
High Concentration

ABSTRACT Aluminum and bisulfite salts inhibit the growth of several fungi and bacteria, and their application effectively controls potato soft rot caused by Erwinia carotovora. In an effort to understand their inhibitory action, ultrastructural changes in Erwinia carotovora subsp. atroseptica after exposure (0 to 20 min) to different concentrations (0.05, 0.1, and 0.2 M) of these salts were examined by using transmission electron microscopy. Plasma membrane integrity was evaluated by using the SYTOX Green fluorochrome that penetrates only cells with altered membranes. Bacteria exposed to all aluminum chloride concentrations, especially 0.2 M, exhibited loosening of the cell walls, cell wall rupture, cytoplasmic aggregation, and an absence of extracellular vesicles. Sodium metabisulfite caused mainly a retraction of plasma membrane and cellular voids which were more pronounced with increasing concentration. Bacterial mortality was closely associated with SYTOX stain absorption when bacteria were exposed to either a high concentration (0.2 M) of aluminum chloride or prolonged exposure (20 min) to 0.05 M aluminum chloride or to a pH of 2.5. Bacteria exposed to lower concentrations of aluminum chloride (0.05 and 0.1 M) for 10 min or less, or to metabisulfite at all concentrations, did not exhibit significant stain absorption, suggesting that no membrane damage occurred or it was too weak to allow the penetration of the stain into the cell. While mortality caused by aluminum chloride involves membrane damage and subsequent cytoplasmic aggregation, sulfite exerts its effect intracellularly; it is transported across the membrane by free diffusion of molecular SO2 with little damage to the cellular membrane.

scholarly journals Length of intact plasma membrane determines the diffusion properties of cellular water

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Sato Eida ◽  
Marc Van Cauteren ◽  
Yuka Hotokezaka ◽  
Ikuo Katayama ◽  
Miho Sasaki ◽  
...  
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Molecular Diffusion ◽  
Apoptotic Cell ◽  
Membrane Integrity ◽  
Biological Tissues ◽  
Critical Determinant ◽  
Adc Value ◽  
Cellular Environment ◽  
Potential Biomarker

Abstract Molecular diffusion in a boundary-free medium depends only on the molecular size, the temperature and medium viscosity. However, the critical determinant of the molecular diffusion property in inhomogeneous biological tissues has not been identified. Here, using an in vitro system and a high-resolution MR imaging technique, we show that the length of the intact plasma membrane is a major determinant of water diffusion in a controlled cellular environment and that the cell perimeter length (CPL) is sufficient to estimate the apparent diffusion coefficient (ADC) of water in any cellular environment in our experimental system (ADC = −0.21 × CPL + 1.10). We used this finding to further explain the different diffusion kinetics of cells that are dying via apoptotic or non-apoptotic cell death pathways exhibiting characteristic changes in size, nuclear and cytoplasmic architectures and membrane integrity. These results suggest that the ADC value can be used as a potential biomarker for cell death.

Melatonin reduces high levels of lipid peroxidation induced by potassium iodate in porcine thyroid

2019 ◽  
pp. 1-7 ◽  
Author(s):  
Paulina Iwan ◽  
Jan Stepniak ◽  
Malgorzata Karbownik-Lewinska
Keyword(s):  
Lipid Peroxidation ◽  
Oxidative Damage ◽  
Membrane Lipids ◽  
Chemical Properties ◽  
Iodine Concentration ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Protective Effects ◽  
Potassium Iodate ◽  
Hormone Synthesis

Abstract. Iodine is essential for thyroid hormone synthesis. Under normal iodine supply, calculated physiological iodine concentration in the thyroid is approx. 9 mM. Either potassium iodide (KI) or potassium iodate (KIO3) are used in iodine prophylaxis. KI is confirmed as absolutely safe. KIO3 possesses chemical properties suggesting its potential toxicity. Melatonin (N-acetyl-5-methoxytryptamine) is an effective antioxidant and free radical scavenger. Study aims: to evaluate potential protective effects of melatonin against oxidative damage to membrane lipids (lipid peroxidation, LPO) induced by KI or KIO3 in porcine thyroid. Homogenates of twenty four (24) thyroids were incubated in presence of either KI or KIO3 without/with melatonin (5 mM). As melatonin was not effective against KI-induced LPO, in the next step only KIO3 was used. Homogenates were incubated in presence of KIO3 (200; 100; 50; 25; 20; 15; 10; 7.5; 5.0; 2.5; 1.25 mM) without/with melatonin or 17ß-estradiol. Five experiments were performed with different concentrations of melatonin (5.0; 2.5; 1.25; 1.0; 0.625 mM) and one with 17ß-estradiol (1.0 mM). Malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) concentration (LPO index) was measured spectrophotometrically. KIO3 increased LPO with the strongest damaging effect (MDA + 4-HDA level: ≈1.28 nmol/mg protein, p < 0.05) revealed at concentrations of around 15 mM, thus corresponding to physiological iodine concentrations in the thyroid. Melatonin reduced LPO (MDA + 4-HDA levels: from ≈0.97 to ≈0,76 and from ≈0,64 to ≈0,49 nmol/mg protein, p < 0.05) induced by KIO3 at concentrations of 10 mM or 7.5 mM. Conclusion: Melatonin can reduce very strong oxidative damage to membrane lipids caused by KIO3 used in doses resulting in physiological iodine concentrations in the thyroid.

Comparision of DNA fragmentantion and plasma membrane integrity between chilled and frozen semen of bulls

2014 ◽  
Author(s):  
Mello Papa Patricia de ◽  
Carlos Ramires Neto ◽  
Priscilla Nascimento Guasti ◽  
Rosiara Rosaria Dias Maziero ◽  
Yame F R Sancler-Silva ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Membrane Integrity ◽  
Plasma Membrane Integrity ◽  
Frozen Semen

Quercetin in attenuation of ischemic/reperfusion injury: A review

2020 ◽  
Vol 13 ◽  
Author(s):  
Milad Ashrafizadeh ◽  
Saeed Samarghandian ◽  
Kiavash Hushmandi ◽  
Amirhossein Zabolian ◽  
Md Shahinozzaman ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Membrane ◽  
Blood Supply ◽  
Apoptotic Cell ◽  
Ischemia Reperfusion ◽  
Membrane Integrity ◽  
Therapeutic Effects ◽  
Molecular Pathways ◽  
Cell Membrane Integrity ◽  
Cell Membrane Disruption

Background: Ischemia/reperfusion (I/R) injury is a serious pathologic event that occurs due to restriction in blood supply to an organ, followed by hypoxia. This condition leads to enhanced levels of pro-inflammatory cytokines such as IL-6 and TNF-, and stimulation of oxidative stress via enhancing reactive oxygen species (ROS) levels. Upon reperfusion, blood supply increases, but it deteriorates condition, and leads to generation of ROS, cell membrane disruption and finally, cell death. Plant derived-natural compounds are well-known due to their excellent antioxidant and anti-inflammatory activities. Quercetin is a flavonoid exclusively found in different vegetables, herbs, and fruits. This naturally occurring compound possesses different pharmacological activities making it appropriate option in disease therapy. Quercetin can also demonstrate therapeutic effects via affecting molecular pathways such as NF-B, PI3K/Akt and so on. Methods: In the present review, we demonstrate that quercetin administration is beneficial in ameliorating I/R injury via reducing ROS levels, inhibition of inflammation, and affecting molecular pathways such as TLR4/NF-B, MAPK and so on. Results and conclusion: Quercetin can improve cell membrane integrity via decreasing lipid peroxidation. Apoptotic cell death is inhibited by quercetin via down-regulation of Bax, and caspases, and upregulation of Bcl-2. Quercetin is able to modulate autophagy (inhibition/induction) in decreasing I/R injury. Nanoparticles have been applied for delivery of quercetin, enhancing its bioavailability and efficacy in alleviation of I/R injury. Noteworthy, clinical trials have also confirmed the capability of quercetin in reducing I/R injury.

scholarly journals Impact of Membrane Lipids on UapA and AzgA Transporter Subcellular Localization and Activity in Aspergillus nidulans

2021 ◽  
Vol 7 (7) ◽  
pp. 514
Author(s):  
Mariangela Dionysopoulou ◽  
George Diallinas
Keyword(s):  
Plasma Membrane ◽  
Subcellular Localization ◽  
Aspergillus Nidulans ◽  
Membrane Lipids ◽  
Membrane Lipid ◽  
Lipid Biosynthesis ◽  
Transport Kinetics ◽  
Negative Effect ◽  
And Function

Recent biochemical and biophysical evidence have established that membrane lipids, namely phospholipids, sphingolipids and sterols, are critical for the function of eukaryotic plasma membrane transporters. Here, we study the effect of selected membrane lipid biosynthesis mutations and of the ergosterol-related antifungal itraconazole on the subcellular localization, stability and transport kinetics of two well-studied purine transporters, UapA and AzgA, in Aspergillus nidulans. We show that genetic reduction in biosynthesis of ergosterol, sphingolipids or phosphoinositides arrest A. nidulans growth after germling formation, but solely blocks in early steps of ergosterol (Erg11) or sphingolipid (BasA) synthesis have a negative effect on plasma membrane (PM) localization and stability of transporters before growth arrest. Surprisingly, the fraction of UapA or AzgA that reaches the PM in lipid biosynthesis mutants is shown to conserve normal apparent transport kinetics. We further show that turnover of UapA, which is the transporter mostly sensitive to membrane lipid content modification, occurs during its trafficking and by enhanced endocytosis, and is partly dependent on autophagy and Hect-type HulARsp5 ubiquitination. Our results point out that the role of specific membrane lipids on transporter biogenesis and function in vivo is complex, combinatorial and transporter-dependent.

scholarly journals Plasma membrane integrity in health and disease: significance and therapeutic potential

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Catarina Dias ◽  
Jesper Nylandsted
Keyword(s):  
Plasma Membrane ◽  
Therapeutic Potential ◽  
Calcium Influx ◽  
Membrane Integrity ◽  
Cell Types ◽  
Physical Parameters ◽  
Membrane Repair ◽  
Plasma Membrane Integrity ◽  
Repair Mechanisms ◽  
And Function

AbstractMaintenance of plasma membrane integrity is essential for normal cell viability and function. Thus, robust membrane repair mechanisms have evolved to counteract the eminent threat of a torn plasma membrane. Different repair mechanisms and the bio-physical parameters required for efficient repair are now emerging from different research groups. However, less is known about when these mechanisms come into play. This review focuses on the existence of membrane disruptions and repair mechanisms in both physiological and pathological conditions, and across multiple cell types, albeit to different degrees. Fundamentally, irrespective of the source of membrane disruption, aberrant calcium influx is the common stimulus that activates the membrane repair response. Inadequate repair responses can tip the balance between physiology and pathology, highlighting the significance of plasma membrane integrity. For example, an over-activated repair response can promote cancer invasion, while the inability to efficiently repair membrane can drive neurodegeneration and muscular dystrophies. The interdisciplinary view explored here emphasises the widespread potential of targeting plasma membrane repair mechanisms for therapeutic purposes.

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