Degradation Of Membrane Phospholipids Research Articles

Thymol application delays the decline of fruit quality in blueberries via regulation of cell wall, energy and membrane lipid metabolism

In this study, we evaluated the potential for exogenous thymol to slow this decline by measuring the effects of thymol application on cell wall, energy, and membrane lipid metabolism. The results showed that thymol application improved the preservation of the total soluble solids, titratable acidity, decay rate, and anthocyanin content, and effectively inhibited the accumulation of O2·-, H2O2, and malondialdehyde in blueberries during storage. Thymol application also effectively maintained fruit firmness, cell wall structure, and energy levels, while delaying the degradation of membrane phospholipids and unsaturated fatty acids during the storage of post-harvest blueberries. Therefore, exogenous thymol can maintain the quality of blueberry fruits by regulating energy and membrane lipid metabolism and reducing cell wall degradation. Thus, thymol-treatment could be a suitable biocontrol agent for maintaining blueberry quality and extending blueberry fruit storage life.

The metabolism of membrane lipid participates in the occurrence of chilling injury in cold-stored banana fruit

Banana fruit is highly vulnerable to chilling injury (CI) during cold storage, which results in quality deterioration and commodity reduction. The purpose of this study was to investigate the membrane lipid metabolism mechanism underlying low temperature-induced CI in banana fruit. Chilling temperature significantly induced CI symptoms in banana fruit, compared to control temperature (22 °C). Using physiological experiments and transcriptomic analyses, we found that chilling temperature (7 °C) increased CI index, malondialdehyde content, and cell membrane permeability. Additionally, chilling temperature upregulated the genes encoding membrane lipid-degrading enzymes, such as lipoxygenase (LOX), phospholipase D (PLD), phospholipase C (PLC), phospholipase A (PLA), and lipase, but downregulated the genes encoding fatty acid desaturase (FAD). Moreover, chilling temperature raised the activities of LOX, PLD, PLC, PLA, and lipase, inhibited FAD activity, lowered contents of unsaturated fatty acids (USFAs) (γ-linolenic acid and linoleic acid), phosphatidylcholine, and phosphatidylinositol, but retained higher contents of saturated fatty acids (SFAs) (stearic acid and palmitic acid), free fatty acids, phosphatidic acid, lysophosphatidic acid, diacylglycerol, a lower USFAs index, and a lower ratio of USFAs to SFAs. Together, these results revealed that chilling temperature-induced chilling injury of bananas were caused by membrane integrity damage and were associated with the enzymatic and genetic manipulation of membrane lipid metabolism. These activities promoted the degradation of membrane phospholipids and USFAs in fresh bananas during cold storage.

Structural, mechanistic, and physiological insights into phospholipase A-mediated membrane phospholipid degradation in Pseudomonas aeruginosa

Cells steadily adapt their membrane glycerophospholipid (GPL) composition to changing environmental and developmental conditions. While the regulation of membrane homeostasis via GPL synthesis in bacteria has been studied in detail, the mechanisms underlying the controlled degradation of endogenous GPLs remain unknown. Thus far, the function of intracellular phospholipases A (PLAs) in GPL remodeling (Lands cycle) in bacteria is not clearly established. Here, we identified the first cytoplasmic membrane-bound phospholipase A1 (PlaF) from Pseudomonas aeruginosa, which might be involved in the Lands cycle. PlaF is an important virulence factor, as the P. aeruginosa ΔplaF mutant showed strongly attenuated virulence in Galleria mellonella and macrophages. We present a 2.0-Å-resolution crystal structure of PlaF, the first structure that reveals homodimerization of a single-pass transmembrane (TM) full-length protein. PlaF dimerization, mediated solely through the intermolecular interactions of TM and juxtamembrane regions, inhibits its activity. The dimerization site and the catalytic sites are linked by an intricate ligand-mediated interaction network, which might explain the product (fatty acid) feedback inhibition observed with the purified PlaF protein. We used molecular dynamics simulations and configurational free energy computations to suggest a model of PlaF activation through a coupled monomerization and tilting of the monomer in the membrane, which constrains the active site cavity into contact with the GPL substrates. Thus, these data show the importance of the PlaF-mediated GPL remodeling pathway for virulence and could pave the way for the development of novel therapeutics targeting PlaF.

Polyethylene-based packaging material loaded with nano-Ag/TiO2 delays quality deterioration of Agaricus bisporus via membrane lipid metabolism regulation

Agaricus bisporus is prone to deteriorate after harvest. In this study, polyethylene-based packaging material loaded with nano-Ag/TiO2 (Nano-PM) was used for the preservation of A. bisporus, and compared with the polyethylene packaging material. The samples were stored at 4 ± 1 ℃ and a relative humidity of 90 % for ten days. Membrane lipid metabolism was taken as a breakthrough point in this study. The cell membrane phenotype and ultrastructure were documented. The changes of key enzyme activities, phospholipids and fatty acids in membrane lipid metabolism were also studied. The results showed that at the end of storage, the electrolyte leakage of the mushrooms in Nano-PM was 19 %, which was lower than that of the control groups (27 %). Nano-PM delayed the decrease of cell membrane fluidity, maintained a good cell structure, also maintained the ascorbic acid (AsA) content, kept glutathione (GSH) and proline at high levels. Furthermore, the phospholipase D (PLD), lipase (LPS) and lipoxygenase (LOX) activities of the mushrooms in Nano-PM were reduced by 16 %, 25 % and 10 % compared with those in control groups. Nano-PM also alleviated the degradation of cell membrane phospholipids and maintained a higher relative content of unsaturated fatty acids. Generally, Nano-PM can delay quality deterioration of A. bisporus by regulating membrane lipid metabolism.

Evidence of altered metabolism of cellular membranes in bipolar disorder comorbid with post-traumatic stress disorder

In proton magnetic resonance spectroscopy (¹H MRS) studies, aberrant levels of choline-containing compounds that include glycerophosphocholine plus phosphocholine (GPC+PC), can signify alterations in the metabolism of cellular membrane phospholipids (MPLs) from a healthy baseline. In a recent ¹H MRS study, we reported increased GPC+PC in cortical and subcortical areas of adult patients with bipolar disorder I (BP-I). Post-traumatic stress disorder (PTSD) can worsen the severity of BP-I, but it is unclear whether the effect of a PTSD comorbidity in BP-I is associated with altered MPL metabolism. The purpose of this study was to re-investigate the ¹H MRS data to determine whether the regional extent of elevated GPC+PC was greater in BP-I patients with PTSD (BP-I/wPTSD) compared to BP-I without comorbid PTSD (BP-I/woPTSD) patients and healthy controls. GPC+PC levels from four brain areas [the anterior cingulate cortex (ACC), anterior-dorsal ACC, caudate, and putamen] were measured in 14 BP-I/wPTSD, 36 BP-I/woPTSD, and 44 healthy controls using a multi-voxel 1H MRS approach on a 3 Tesla system with high spatial resolution and absolute quantification. Results show a significant increase in GPC+PC levels from the caudate and putamen of BP-I/wPTSD patients compared to healthy controls (P<0.05) and in the putamen compared to BP-I/woPTSD patients (P<0.05). These findings are consistent with evidence of elevated degradation of MPLs in the neuropil that is more pronounced in BP-I patients with comorbid PTSD.

PuMYB21/PuMYB54 coordinate to activate PuPLD\u03b21 transcription during peel browning of cold-stored \u201cNanguo\u201d pears

Refrigeration is commonly used to extend the storage life of “Nanguo” pears, but fruit in long-term refrigeration is prone to peel browning, which is related to membrane lipid degradation. To determine the mechanism of membrane lipid degradation, we identified two R2R3-MYB transcription factors (TFs), PuMYB21 and PuMYB54, from “Nanguo” pears, which were notably expressed in response to cold stress and during the peel-browning process. The results from yeast one-hybrid, electrophoretic mobility shift, and transient expression assays indicated that both PuMYB21 and PuMYB54 directly bind to the promoter of PuPLDβ1 (a key enzyme catalyzing the hydrolysis of membrane phospholipids) and activate its expression, which probably enhances the degradation of membrane phospholipids and eventually results in peel browning. Moreover, the overexpression of PuMYB21 and PuMYB54 can greatly activate the transcription of endogenous PuPLDβ1 in both “Nanguo” pear fruits and calli, and their silencing can inhibit its transcription. Furthermore, yeast two-hybrid, bimolecular fluorescence complementation, and pull-down assays verified that PuMYB21 interacts with PuMYB54 to enhance the expression of PuPLDβ1. In summary, we demonstrate that PuMYB21 and PuMYB54 may have roles in membrane lipid metabolism by directly binding to the downstream structural gene PuPLDβ1 during the low temperature-induced peel browning of “Nanguo” pears.

Aging-Related and Gender Specific Albumin Misfolding in Alzheimer's Disease.

Aging-related protein misfolding and aggregation may play critical roles in the pathogenesis of numerous diseases. In the brain, extracellular aggregated amyloid-β (Aβ) is closely related to the death of neurons in individuals with Alzheimer’s disease (AD). Albumin-Aβ binding is important in preventing Aβ fibril aggregation. However, because albumin is the most abundant and important antioxidant in the circulation, aging-related oxidative stress could have a significant effect on the molecular conformation and binding capacities of albumin. To investigate the link between misfolded albumin and AD, we developed fluorescent assays to determine the effects of misfolded albumin on membrane integrity in the presence of a lipolytic, inflammatory response-like enzyme, secretory phospholipase A2 (sPLA2). We found that misfolded albumin increased degradation of phospholipids in highly fluid bilayer membranes in the presence of sPLA2 due to hydrophobic effects of misfolded albumin. High amounts of misfolded albumin were present in sera of elderly (average 74 years) versus young (average 24 years) subjects (p < 0.0001). Albumin in cerebrospinal fluid (CSF) of elderly subjects, though present in small concentrations, had a 2- to 3-fold increased capacity to promote sPLA2-catalyzed membrane phospholipid degradation as compared with the same amount of albumin in serum (p < 0.0001). In addition, the fatty acid binding capacity of albumin in CSF from female subjects was considerably lower than values obtained for men, especially for individuals diagnosed with AD (p = 0.0006). This study suggests that inflammation, misfolded albumin and/or other dysfunctional proteins, and changes in membrane fluidity could alter cell membrane integrity and homeostasis and contribute to the pathogenesis of aging-related dementia and AD.

Influence of the endocannabinoid system on memory processes

The endocannabinoid system (ECS) is a lipid signaling system, which consists of the endocannabinoids (EC) anandamide (AEA) and 2-arachidonylglycerol (2-AG), the cannabinoid receptors (CB1 and CB2), and the enzymes that regulate their production and degradation. AEA and 2-AG are lipid compounds derived presynaptically from the degradation of membrane phospholipids and act as key modulators on synaptic transmission. This article presents accumulated data on the mechanisms by which ECS affects learning and memory. Substances that modulate the activity of ECS have impact on different phases of memory formation through direct and indirect influences. Studies show contradictory results on the role of the ECS in learning and memory processes.

Reactive Oxygen Species as Potential Drivers of the Seed Aging Process.

Seeds are an important life cycle stage because they guarantee plant survival in unfavorable environmental conditions and the transfer of genetic information from parents to offspring. However, similar to every organ, seeds undergo aging processes that limit their viability and ultimately cause the loss of their basic property, i.e., the ability to germinate. Seed aging is a vital economic and scientific issue that is related to seed resistance to an array of factors, both internal (genetic, structural, and physiological) and external (mainly storage conditions: temperature and humidity). Reactive oxygen species (ROS) are believed to initiate seed aging via the degradation of cell membrane phospholipids and the structural and functional deterioration of proteins and genetic material. Researchers investigating seed aging claim that the effective protection of genetic resources requires an understanding of the reasons for senescence of seeds with variable sensitivity to drying and long-term storage. Genomic integrity considerably affects seed viability and vigor. The deterioration of nucleic acids inhibits transcription and translation and exacerbates reductions in the activity of antioxidant system enzymes. All of these factors significantly limit seed viability.

Leptospiral phosphatidylinositol-specific phospholipase C: a novel conserved antigen for the definitive diagnosis of Leptospirosis.

Identification and characterisation of novel antigenic proteins of Leptospira are necessary to unravel the secrets of the Leptospiral disease biology. Besides, the current scenario of Leptospirosis demands the development of advanced diagnostics with the potential of an early and specific diagnosis. This work reports the diagnostic efficacy of a PI-PLC (LA_1375) of Leptospira interrogans serovar Lai strain 56601. Phospholipases are enzymes that catalyse the degradation of membrane phospholipids, with the after effects of pathophysiological consequences through the impairment of cellular signalling mechanisms. The immunoblotting analysis allows to identify the Leptospirosis positive serum samples demonstrated the expression and exposure of the protein to the immune system and confirmed the antigenic nature of the protein. Furthermore, evaluation of diagnostic efficacy of an ELISA to detect antibodies against recombinant PI-PLC has tested in indirect IgM ELISA using the purified 50kDa recombinant protein as the coating antigen. A cut-off value of 0.218at mean + 2SD and a sensitivity value of 100% and a specificity value of 95.65% explored for the rPI-PLC IgM ELISA. The PPV and NPV of ELISA for the Leptospirosis confirmed acute phase samples were 95.87% and 100% respectively. Comparison of the ELISA assay with MAT for the detection of Leptospiral antibodies showed a positive correlation (r value 0.345, p < 0.05), and signified the diagnostic efficacy of rPI-PLC for the definitive diagnosis of the Leptospirosis. In addition, the revealed conservation nature of PI-PLC among different Leptospira species highlights the diagnostic and vaccine candidate potential. Thus, the study emphasises the Leptospiral PI-PLC as a potential antigen still the importance as a novel biomarker candidate for the serodiagnosis and pathogenesis of Leptospirosis have to be investigated.

Phomopsis longanae-induced pericarp browning and disease development of longan fruit can be alleviated or aggravated by regulation of ATP-mediated membrane lipid metabolism

Compared to P. longanae-inoculated longan fruit, DNP-treated P. longanae-inoculated longans displayed higher fruit disease index, pericarp browning index and cell membrane permeability. Moreover, they exhibited higher activities of phospholipase D, lipase and lipoxygenase, lower amounts of phosphatidylcholine, phosphatidylinositol and USFA (unsaturated fatty acids) as well as higher amounts of phosphatidic acid and SFA (saturated fatty acids). Additionally, lower ratio of USFA to SFA and USFA index were shown in DNP-treated P. longanae-inoculated longans. However, ATP-treated P. longanae-inoculated longans exhibited the opposite results. These findings indicated that DNP stimulated longan pericarp browning and disease development caused by P. longanae resulted from the increases in activities of membrane lipids-degrading enzymes, promoting degradation of membrane phospholipids and USFA, and disruption of membrane structural integrity. Whereas, the opposite results observed in ATP-treated P. longanae-inoculated longans were due to the reduction in activities of membrane lipids-degrading enzymes and the maintenance of membrane structural integrity.

Lasiodiplodia theobromae (Pat.) Griff. & Maubl.-induced disease development and pericarp browning of harvested longan fruit in association with membrane lipids metabolism

Effects of Lasiodiplodia theobromae inoculation on disease development, pericarp browning and membrane lipids metabolism of harvested “Fuyan” longan fruit were studied. Compared with control fruit, L. theobromae-inoculated longans showed higher fruit disease index, pericarp browning index and cell membrane permeability, as well as higher activities of phospholipase D, lipase and lipoxygenase. Additionally, there were lower contents of membrane phospholipids but higher content of phosphatidic acid, and lower level of unsaturated fatty acids but higher level of saturated ones with lower ratio of unsaturated fatty acid to saturated fatty acid and lower index of unsaturated fatty acids in pericarp of L. theobromae-inoculated longans. These results suggested that L. theobromae-induced disease development and pericarp browning of harvested longans might be attributed to the damaged cellular membrane structural integrity, induced by the activated membrane lipids-degrading enzymes increasing the degradation of membrane phospholipids and unsaturated fatty acids in pericarp of harvested longan fruit.

Inhibition of phospholipase D enzyme activity through hexanal leads to delayed mango (Mangifera indica L.) fruit ripening through changes in oxidants and antioxidant enzymes activity

Fruit ripening is a senescence process and phospholipase D (PLD) is a key enzyme causing degradation of membrane phospholipids during that process. Our earlier studies showed that hexanal, is known to inhibit the PLD activity. The objectives were (i) to quantify the effects of postharvest hexanal treatment in mango fruit on physiochemical traits, (ii) to assess the changes in oxidants, antioxidants, and antioxidant enzymes activity in mango fruit after hexanal treatment. Fully matured mango fruit, var. Neelum were harvested from the tree, dipped in 0.02% hexanal solution, and stored under ambient conditions to study the physio and biochemical changes during storage period. The results indicated that hexanal treatment significantly reduced ethylene evolution rate, oxidants content and PLD enzyme activity in the fruit compared with control, key factors to delay ripening and senescence in fruit. However, the activities of antioxidant enzymes like superoxide dismutase, catalase, ascorbate peroxidase, glutathione peroxidase and the contents of ascorbic acid were increased in response to hexanal treatment. The decreased ethylene evolution rate, PLD enzyme activity and oxidant production caused by hexanal treatment might have led to increased shelf life. Overall, the results suggest that post-harvest dip of mango fruits in 0.02% hexanal solution extended the shelf life of mango fruit under ambient storage conditions, without the loss of quality of fruits.

New Prognostic Biomarkers in Patients With Traumatic Brain Injury.

Context:Traumatic brain injury (TBI) is a leading cause of death, disability, and resource consumption per year. There are two kinds of brain injury in TBI, primary and secondary injuries. Primary injury refers to the initial physical forces applied to the brain at the moment of impact. Secondary injury occurs over a period of hours or days following the initial trauma and results from the activation of different pathways such as inflammation, coagulation, oxidation, and apoptosis.Evidence Acquisition:This review focuses on new prognostic biomarkers of mortality in TBI patients related to inflammation, coagulation, oxidation, and apoptosis.Results:Recently circulating levels of substance P (SP), soluble CD40 ligand (sCD40L), tissue inhibitor of matrix metalloproteinases (TIMP)-1, malondialdehyde (MDA), and cytokeratin (CK)-18 fragmented have been found to be associated with mortality in TBI patients. Substance P is a neuropeptide of the tachykinin family, mainly synthesized in the central and peripheral nervous system, with proinflammatory effects when binding to their neurokinin-1 receptor (NK1R). Soluble CD40 ligand, a member of the tumor necrosis factor (TNF) family that is released into circulation from activated platelets, exhibit proinflamatory, and procoagulant properties on binding to their cell surface receptor CD40. Matrix metalloproteinases (MMPs) are a family of zinc-containing endoproteinases involved neuroinflammation and TIMP-1 is the inhibitor of some of them. Malondialdehyde is an end-product formed during lipid peroxidation due to degradation of cellular membrane phospholipids, that is released into extracellular space and finally into the blood. Cytokeratin -18 is cleaved by the action of caspases during apoptosis, and CK-18 fragmented is released into the blood.Conclusions:Circulating levels of some biomarkers, such as SP, sCD40L, TIMP-1, MDA, and CK-18 fragmented, related to inflammation, coagulation, oxidation, and apoptosis have been recently associated with mortality in patients with TBI. These biomarkers could help in the prognostic classification of the patients and open new research lines in the treatment of patients with TBI.

Phospholipid alterations in the brain and heart in a rat model of asphyxia-induced cardiac arrest and cardiopulmonary bypass resuscitation.

Cardiac arrest (CA) induces whole-body ischemia, causing damage to multiple organs. Ischemic damage to the brain is mainly responsible for patient mortality. However, the molecular mechanism responsible for brain damage is not understood. Prior studies have provided evidence that degradation of membrane phospholipids plays key roles in ischemia/reperfusion injury. The aim of this study is to correlate organ damage to phospholipid alterations following 30min asphyxia-induced CA or CA followed by cardiopulmonary bypass (CPB) resuscitation using a rat model. Following 30min CA and CPB resuscitation, rats showed no brain function, moderately compromised heart function, and died within a few hours; typical outcomes of severe CA. However, we did not find any significant change in the content or composition of phospholipids in either tissue following 30min CA or CA followed by CPB resuscitation. We found a substantial increase in lysophosphatidylinositol in both tissues, and a small increase in lysophosphatidylethanolamine and lysophosphatidylcholine only in brain tissue following CA. CPB resuscitation significantly decreased lysophosphatidylinositol but did not alter the other lyso species. These results indicate that a decrease in phospholipids is not a cause of brain damage in CA or a characteristic of brain ischemia. However, a significant increase in lysophosphatidylcholine and lysophosphatidylethanolamine found only in the brain with more damage suggests that impaired phospholipid metabolism may be correlated with the severity of ischemia in CA. In addition, the unique response of lysophosphatidylinositol suggests that phosphatidylinositol metabolism is highly sensitive to cellular conditions altered by ischemia and resuscitation.

ВПЛИВ ІНФУЗІЙНИХ РОЗЧИНІВ ЛАКТОПРОТЕЇНУ З СОРБІТОЛОМ ТА HAESLX- 5% НА БІОХІМІЧНІ МАРКЕРИ ФІБРОГЕНЕЗУ ЛЕГЕНЕВОЇ ТКАНИНИ В ЩУРІВ З ОПІКОВОЮ ТРАВМОЮ ШКІРИ

&lt;p&gt;&lt;strong&gt;INFLUENCE &lt;/strong&gt;&lt;strong&gt;of&lt;/strong&gt;&lt;strong&gt; &lt;/strong&gt;&lt;strong&gt;laktoprotein&lt;/strong&gt;&lt;strong&gt;um&lt;/strong&gt;&lt;strong&gt; with sorbitol and HAES-LX-5% infusion&lt;/strong&gt;&lt;strong&gt;’S&lt;/strong&gt;&lt;strong&gt; solutions &lt;/strong&gt;&lt;strong&gt;on&lt;/strong&gt;&lt;strong&gt; biochemical markers of fibrogenesis lung tissue in rats with &lt;/strong&gt;&lt;strong&gt;skin&lt;/strong&gt;&lt;strong&gt; burn trauma &lt;/strong&gt;&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Ocheretnyuk&lt;/strong&gt;&lt;strong&gt; &lt;/strong&gt;&lt;strong&gt;A&lt;/strong&gt;&lt;strong&gt;.А. &lt;/strong&gt;&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;VinnytsiaNationalMedicalUniversityby M.I. Pyrogov &lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary. &lt;/strong&gt;It is shown that in a case of burn disease, especially on day 3, remodeling of connective tissue and oxidative damage phospholipid lungs takes place. Infusion of colloidal hyperosmolar solution - HAES-LX- 5% and lactoproteinum solution with sorbitol equally causes antifibrogenic effect and reduces the severity of oxidative degradation of membrane phospholipids in rats with skin burns. Their protective effect is the most expressive on day 7 of the experiment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Keywords:&lt;/strong&gt; infusion therapy, fibrogenesis, phospholipids, HAES-LX-5%, lactoproteinum with sorbitol.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Introduction.&lt;/strong&gt;&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;Trigger mechanisms for alteration of lung tissue under conditions of skin burn injuries is considered a development of oxidative stress accompanied by accumulation of oxidative modification of lipids and destruction of cell membranes. This process is characterized also by remodeling of connective tissue and activation of fibrogenesis processes in the lung tissues. It is quite clear that the efficacy of potential correctors of the lung functional condition is largely determined by their ability to contain the accumulation of reactive free radicals, reduce lesion of bi-lipidic layer of cell membranes, and to detect depressing effect on fibrogenesis in the lung tissue.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="-1"&gt;&lt;strong&gt;Methods.&lt;/strong&gt;&lt;/p&gt;&lt;p class="-1"&gt;The contents of biochemical studies: serum samples were tested for markers of degradation of connective tissue and fibrogenesis (free oxyproline, transforming growth factor-β1), lung homogenate was tested for contents of phosphatidylcholine and &lt;a href="http://www.multitran.ru/c/m.exe?t=5341349_1_2&amp;amp;s1=%EB%E8%E7%EE%F4%EE%F1%F4%E0%F2%E8%E4%E8%EB%F5%EE%EB%E8%ED"&gt;lysophosphatidylcholine&lt;/a&gt;.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results and discussion.&lt;/strong&gt;&lt;/p&gt;&lt;p class="-1"&gt;Skin burn injury causes diverse biochemical and pathophysiological changes in rats in whole and particularly in the lung tissue. Our research has shown that burn disease is accompanied by distortion of phospholipid spectrum of lung tissue, which manifested by decrease of phosphatidylcholine content and increase of its oxidation product - &lt;a href="http://www.multitran.ru/c/m.exe?t=5341349_1_2&amp;amp;s1=%EB%E8%E7%EE%F4%EE%F1%F4%E0%F2%E8%E4%E8%EB%F5%EE%EB%E8%ED"&gt;lysophosphatidylcholine&lt;/a&gt;. Covalent modification of phospholipid membranes in case of burn disease leads to disruption of the permeability of cell membranes and disorders in the cellular pumps required to transport materials and create ion concentration gradient on both sides of cell membrane. Along with these changes, the burn disease is characterized by connective tissue remodeling and fibrogenesis processes activation, as convincingly proved by growth in serum free oxyproline and transforming growth factor TGF-β1. Pharmacological correction of burn disease using HAES-LX-5% and lactoproteinum with sorbitol solutions somewhat normalized ratio of phosphatidylcholine/&lt;a href="http://www.multitran.ru/c/m.exe?t=5341349_1_2&amp;amp;s1=%EB%E8%E7%EE%F4%EE%F1%F4%E0%F2%E8%E4%E8%EB%F5%EE%EB%E8%ED"&gt;lysophosphatidylcholine&lt;/a&gt; in cell membranes of the lung tissue and prevented remodeling of connective tissue and fibrogenesis activation. HAES -LX-5% was proven at least not inferior versus a reference medicine - lactoproteinum with sorbitol- in terms of the above-said effects.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions.&lt;/strong&gt;&lt;/p&gt;&lt;p class="-1"&gt;Skin burn injury in rats accompanied by the development of lung imbalance of lung phospholipids (phosphatidylcholine content reduced by 35-47% and the &lt;a href="http://www.multitran.ru/c/m.exe?t=5341349_1_2&amp;amp;s1=%EB%E8%E7%EE%F4%EE%F1%F4%E0%F2%E8%E4%E8%EB%F5%EE%EB%E8%ED"&gt;lysophosphatidylcholine&lt;/a&gt; grew by 34-66%) and increasing content of connective tissue destruction (free oxyproline - by 60-97%) and fibrogenesis (TGF-β1 – by 58-137%) markers in serum.&lt;/p&gt;&lt;p class="-1"&gt;Administration of colloidal-osmotic solution HAES-LX-5% and lactoproteinum with sorbitol suppressed development of connective tissue remodeling processes of fibrogenesis and oxidative lesion of lungs phosphorlipidic bilayer.&lt;/p&gt;

Serum malondialdehyde levels in patients with malignant middle cerebral artery infarction are associated with mortality.

ObjectiveMalondialdehyde (MDA) is an end-product formed during lipid peroxidation, due to degradation of cellular membrane phospholipids. MDA is released into extracellular space and finally into the blood; it has been used as an effective biomarker of lipid oxidation. High circulating levels of MDA have been previously described in patients with ischemic stoke than in controls, and an association between circulating MDA levels and neurological functional outcome in patients with ischemic stoke. However, an association between serum MDA levels and mortality in patients with ischemic stroke has not been previously reported, and that was the objective of this study.MethodsObservational, prospective and multicenter study performed in six Intensive Care Units. We included patients with severe malignant middle cerebral artery infarction (MMCAI) defined as Glasgow Coma Scale (GCS) lower than 9. We measured serum MDA levels in 50 patients with severe MMCAI at the time of diagnosis and in 100 healthy subjects. Mortality at 30 days was the end point of the study.ResultsWe found that patients with severe MMCAI showed higher serum MDA levels than healthy subjects (p<0.001). We found higher serum MDA levels (p<0.001) in non-surviving MMCAI patients (n=26) than in survivors (n=24). The area under the curve for prediction of 30-day mortality for serum MDA levels was 0.77 (95% CI = 0.63-0.88; p<0.001). Serum MDA levels >2.27 nmol/mL were associated with 30-day mortality (OR=7.23; 95% CI=1.84-28.73; p=0.005) controlling for GCS and age on multiple binomial logistic regression analysis.ConclusionsTo our knowledge, this is the first study showing that serum malondialdehyde levels in patients with MMCAI are associated with early mortality.

Metabolomic study in plasma, liver and kidney of mice exposed to inorganic arsenic based on mass spectrometry

The mechanism of arsenic toxicity still remains unclear, although enzymatic inhibition, impaired antioxidants metabolism and oxidative stress may play a role. The toxicological effects of trivalent inorganic arsenic on laboratory mouse Mus musculus after oral administration (3 mg/kg body weight/day) were investigated along 12 days, using a metabolomic approach based on direct infusion mass spectrometry to polar and lipophilic extracts from different organs and fluids (liver, kidney, and plasma). Positive and negative acquisition modes (ESI(+)/ESI(-)) were used throughout the experiments. The most significant endogenous metabolites affected by exposure were traced by partial least square-discriminant analysis and confirmed by tandem mass spectrometry (MS/MS) and gas chromatography coupled to MS. In this work, the toxic effect of arsenic has been related with important metabolic pathways, such as energy metabolism (e.g., glycolysis, Krebs cycle), amino acids metabolism, choline metabolism, methionine cycle, and degradation of membrane phospholipids (cell apoptosis). In addition, this work illustrates the high reliability of mass spectrometry based on a metabolomic approach to study the biochemical effects induced by metal exposure.

Internalization ofClostridium perfringensα-toxin leads to ERK activation and is involved on its cytotoxic effect

Clostridium perfringens phospholipase C (CpPLC), also called α-toxin, plays a key role in the pathogenesis of gas gangrene. CpPLC may lead to cell lysis at concentrations that cause extensive degradation of plasma membrane phospholipids. However, at sublytic concentrations it induces cytotoxicity without inducing evident membrane damage. The results of this work demonstrate that CpPLC becomes internalized in cells by a dynamin-dependent mechanism and in a time progressive process: first, CpPLC colocalizes with caveolin both at the plasma membrane and in vesicles, and later it colocalizes with early and late endosomes and lysosomes. Lysosomal damage in the target cells is evident 9 h after CpPLC exposure. Our previous work demonstrated that CpPLCinduces ERK1/2 activation, which is involved in its cytotoxic effect. In this work we found that cholesterol sequestration, dynamin inhibition, as well as inhibition of actin polymerization, prevent CpPLC internalization and ERK1/2 activation, involving endocytosis in the signalling events required for CpPLC cytotoxic effect at sublytic concentrations. These results provide new insights about the mode of action of this bacterial phospholipase C, previously considered to act only locally on cell membrane.

Interplay between ABA and phospholipases A2 and D in the response of citrus fruit to postharvest dehydration

The interplay between abscisic acid (ABA) and phospholipases A2 and D (PLA2 and PLD) in the response of citrus fruit to water stress was investigated during postharvest by using an ABA-deficient mutant from 'Navelate' orange named 'Pinalate'. Fruit from both varieties harvested at two different maturation stages (mature-green and full-mature) were subjected to prolonged water loss inducing stem-end rind breakdown (SERB) in full-mature fruit. Treatment with PLA2 inhibitor aristolochic acid (AT) and PLD inhibitor lysophosphatidylethanolamine (LPE) reduced the disorder in both varieties, suggesting that phospholipid metabolism is involved in citrus peel quality. Expression of CsPLDα and CsPLDβ, and CssPLA2α and CssPLA2β was studied by real-time RT-PCR during water stress and in response to ABA. CsPLDα expression increased in mature-green fruit from 'Navelate' but not in 'Pinalate' and ABA did not counteract this effect. ABA enhanced repression of CsPLDα in full-mature fruit. CsPLDβ gene expression decreased in mature-green 'Pinalate', remained unchanged in 'Navelate' and was induced in full-mature fruit from both varieties. CssPLA2α expression increased in mature-green fruit from both varieties whereas in full-mature fruit only increased in 'Navelate'. CssPLA2β expression increased in mature-green flavedo from both varieties, but in full-mature fruit remained steady in 'Navelate' and barely increased in 'Pinalate' fruit. ABA reduced expression in both after prolonged storage. Responsiveness to ABA increased with maturation. Our results show interplay between PLA2 and PLD and suggest that ABA action is upstream phospholipase activation. Response to ABA during water stress in citrus is regulated during fruit maturation and involves membrane phospholipid degradation.