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phosphatidylserine, brain

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https://www.readbyqxmd.com/read/28915027/structure-and-dynamics-of-membrane-proteins-and-membrane-associated-proteins-with-native-bicelles-from-eukaryotic-tissues
#1
Sean T Smrt, Adrian W Draney, Indira Singaram, Justin L Lorieau
In vitro studies of protein structure, function and dynamics typically preclude the complex range of molecular interactions found in living tissues. In vivo studies elucidate these complex relationships, yet they are typically incompatible with the extensive and controlled biophysical experiments available in vitro. We present an alternative approach by extracting membranes from eukaryotic tissues to produce native bicelles to capture the rich and complex molecular environment of in vivo studies while retaining the advantages of in vitro experiments...
September 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/28903085/multiscale-molecular-dynamics-simulations-of-lipid-interactions-with-p-glycoprotein-in-a-complex-membrane
#2
Laura Domicevica, Heidi Koldsø, Philip C Biggin
P-glycoprotein (P-gp) can transport a wide range of very different hydrophobic organic molecules across the membrane. Its ability to extrude molecules from the cell creates delivery problems for drugs that target proteins in the central nervous system (CNS) and also causes drug-resistance in many forms of cancer. Whether a drug will be susceptible to export by P-gp is difficult to predict and currently this is usually assessed with empirical and/or animal models. Thus, there is a need to better understand how P-gp works at the molecular level in order to fulfil the 3Rs: Refinement, reduction and replacement of animals in research...
September 2, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28903038/lipidomic-and-transcriptomic-basis-of-lysosomal-dysfunction-in-progranulin-deficiency
#3
Bret M Evers, Carlos Rodriguez-Navas, Rachel J Tesla, Janine Prange-Kiel, Catherine R Wasser, Kyoung Shin Yoo, Jeffrey McDonald, Basar Cenik, Thomas A Ravenscroft, Florian Plattner, Rosa Rademakers, Gang Yu, Charles L White, Joachim Herz
Defective lysosomal function defines many neurodegenerative diseases, such as neuronal ceroid lipofuscinoses (NCL) and Niemann-Pick type C (NPC), and is implicated in Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD-TDP) with progranulin (PGRN) deficiency. Here, we show that PGRN is involved in lysosomal homeostasis and lipid metabolism. PGRN deficiency alters lysosome abundance and morphology in mouse neurons. Using an unbiased lipidomic approach, we found that brain lipid composition in humans and mice with PGRN deficiency shows disease-specific differences that distinguish them from normal and other pathologic groups...
September 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/28870843/phosphatidylserine-a-cancer-cell-targeting-biomarker
#4
REVIEW
Bhupender Sharma, Shamsher S Kanwar
Cancer is a leading cause of mortality and morbidity globally. Many prominent cancer-associated molecules have been identified over the recent years which include EGFR, CD44, TGFbRII, HER2, miR-497, NMP22, BTA, Fibrin/FDP etc. These biomarkers are often used for screening, detection, diagnosis, prognosis, prediction and monitoring of cancer development. Phosphatidylserine (PS) is an essential component in all human cells which is present on the inner leaflet of the cell membrane. The oxidative stress causes exposure of PS on the surface of the vascular endothelium in the cancer cells (lung, breast, pancreatic, bladder, skin, brain metastasis, rectal adenocarcinoma etc...
September 1, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28851448/dietary-arachidonic-acid-increases-deleterious-effects-of-amyloid-%C3%AE-oligomers-on-learning-abilities-and-expression-of-ampa-receptors-putative-role-of-the-acsl4-cpla2-balance
#5
Mélanie H Thomas, Cédric Paris, Mylène Magnien, Julie Colin, Sandra Pelleïeux, Florence Coste, Marie-Christine Escanyé, Thierry Pillot, Jean-Luc Olivier
BACKGROUND: Polyunsaturated fatty acids play a crucial role in neuronal function, and the modification of these compounds in the brain could have an impact on neurodegenerative diseases such as Alzheimer's disease. Despite the fact that arachidonic acid is the second foremost polyunsaturated fatty acid besides docosahexaenoic acid, its role and the regulation of its transfer and mobilization in the brain are poorly known. METHODS: Two groups of 39 adult male BALB/c mice were fed with an arachidonic acid-enriched diet or an oleic acid-enriched diet, respectively, for 12 weeks...
August 29, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28807933/mice-deficient-in-lysophosphatidic-acid-acyltransferase-%C3%AE-lpaat%C3%AE-acylglycerophosphate-acyltransferase-4-agpat4-have-impairments-in-spatial-learning-and-memory-associated-with-reductions-in-nmda-and-ampa-receptors
#6
Ryan M Bradley, Emily B Mardian, Darin Bloemberg, Juan J Aristizabal Henao, Andrew S Mitchell, Phillip M Marvyn, Katherine A Moes, Ken D Stark, Joe Quadrilatero, Robin E Duncan
We previously characterized LPAATδ/AGPAT4 as a mitochondrial lysophosphatidic acid acyltransferase that regulates brain levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI). Here we report that Lpaatδ (-/-) mice display impaired spatial learning and memory compared to wildtype littermates in the Morris Water Maze, and investigated potential mechanisms associated with brain phospholipid changes. Marker protein immunoblotting suggested that the relative brain content of neurons, glia, and oligodendrocytes was unchanged...
August 14, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28760485/phospholipid-class-specific-brain-enrichment-in-response-to-lysophosphatidylcholine-docosahexaenoic-acid-infusion
#7
Raphaël Chouinard-Watkins, Chuck T Chen, Adam H Metherel, R J Scott Lacombe, Frank Thies, Mojgan Masoodi, Richard P Bazinet
Recent studies suggest that at least two pools of plasma docosahexaenoic acid (DHA) can supply the brain: non-esterified DHA (NE-DHA) and lysophosphatidylcholine (lysoPtdCho)-DHA. In contrast to NE-DHA, brain uptake of lysoPtdCho-DHA appears to be mediated by a specific transporter, but whether both forms of DHA supply undergo the same metabolic fate, particularly with regards to enrichment of specific phospholipid (PL) subclasses, remains to be determined. This study aimed to evaluate brain uptake of NE-DHA and lysoPtdCho-DHA into brain PL classes...
October 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28698592/monitoring-changes-of-docosahexaenoic-acid-containing-lipids-during-the-recovery-process-of-traumatic-brain-injury-in-rat-using-mass-spectrometry-imaging
#8
Shuai Guo, Dan Zhou, Mo Zhang, Tiejun Li, Yujie Liu, Yupin Xu, Tianjing Chen, Zhili Li
Brain lipid homoeostasis is critical during recovery process after traumatic brain injury (TBI). In this study, we integrated liquid extraction and electrosonic spray ionization technology to develop an ionization device coupled with a Fourier transform ion cyclotron resonance mass spectrometer for imaging of docosahexaenoic acid (DHA)-containing lipids on rat brain tissues. The ion images of the brain tissue sections from the normal rats and the rats after TBI at acute phase (0 and 1 day) and chronic phase (3, 5, and 7 days) were obtained...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28672041/comprehensive-identification-of-age-related-lipidome-changes-in-rat-amygdala-during-normal-aging
#9
Roman Šmidák, Harald C Köfeler, Harald Hoeger, Gert Lubec
Brain lipids are integral components of brain structure and function. However, only recent advancements of chromatographic techniques together with mass spectrometry allow comprehensive identification of lipid species in complex brain tissue. Lipid composition varies between the individual areas and the majority of previous reports was focusing on individual lipids rather than a lipidome. Herein, a mass spectrometry-based approach was used to evaluate age-related changes in the lipidome of the rat amygdala obtained from young (3 months) and old (20 months) males of the Sprague-Dawley rat strain...
2017: PloS One
https://www.readbyqxmd.com/read/28654387/phosphatidylserine-targeted-nanotheranostics-for-brain-tumor-imaging-and-therapeutic-potential
#10
Lulu Wang, Amyn A Habib, Akiva Mintz, King C Li, Dawen Zhao
Phosphatidylserine (PS), the most abundant anionic phospholipid in cell membrane, is strictly confined to the inner leaflet in normal cells. However, this PS asymmetry is found disruptive in many tumor vascular endothelial cells. We discuss the underlying mechanisms for PS asymmetry maintenance in normal cells and its loss in tumor cells. The specificity of PS exposure in tumor vasculature but not normal blood vessels may establish it a useful biomarker for cancer molecular imaging. Indeed, utilizing PS-targeting antibodies, multiple imaging probes have been developed and multimodal imaging data have shown their high tumor-selective targeting in various cancers...
January 1, 2017: Molecular Imaging
https://www.readbyqxmd.com/read/28570999/in-vitro-and-in-vivo-cytotoxic-activity-of-human-lactoferricin-derived-antitumor-peptide-r-dim-p-lf11-334-on-human-malignant-melanoma
#11
Sabrina Riedl, Beate Rinner, Helmut Schaider, Bernadette Liegl-Atzwanger, Katharina Meditz, Julia Preishuber-Pflügl, Sarah Grissenberger, Karl Lohner, Dagmar Zweytick
Di-peptides derived from the human host defense peptide lactoferricin were previously described to specifically interact with the negatively charged lipid phosphatidylserine exposed by cancer cells. In this study one further derivative, namely R-DIM-P-LF11-334 is shown to exhibit even increased cancer toxicity in vitro and in vivo while non-neoplastic cells are not harmed.In liposomal model systems composed of phosphatidylserine mimicking cancerous and phosphatidylcholine mimicking non-cancerous membranes the specific interaction with the cancer marker PS was confirmed by specific induction of membrane perturbation and permeabilization in presence of the peptide...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28431519/semi-automatic-synthesis-and-biodistribution-of-n-2-18-f-fluoropropionyl-bis-zinc-ii-dipicolylamine-18-f-fp-dpazn2-for-ad-model-imaging
#12
Fuhua Wen, Dahong Nie, Kongzhen Hu, Ganghua Tang, Shaobo Yao, Caihua Tang
BACKGROUND: Phosphatidylserine (PS)-targeting positron emission tomography (PET) imaging with labeled small-molecule tracer is a crucial non-invasive molecule imaging method of apoptosis. In this study, semi-automatic radiosynthesis and biodistribution of N-(2-(18)F-fluoropropionyl)-bis(zinc(II)-dipicolylamine) ((18)F-FP-DPAZn2), as a potential small-molecule tracer for PET imaging of cell death in Alzheimer's disease (AD) model, were performed. METHODS: (18)F-FP-DPAZn2 was synthesized on the modified PET-MF-2V-IT-I synthesizer...
April 21, 2017: BMC Medical Imaging
https://www.readbyqxmd.com/read/28414573/phosphatidylserine-translocation-after-radiosurgery-in-an-animal-model-of-arteriovenous-malformation
#13
Newsha Raoufi Rad, Lucinda S McRobb, Zhenjun Zhao, Vivienne S Lee, Nirav J Patel, Anas Sarwar Qureshi, Michael Grace, Joshua J McHattan, Jude V Amal Raj, Hong Duong, Saleh R Kashba, Marcus A Stoodley
Phosphatidylserine (PS) is asymmetrically distributed across the plasma membrane, located predominantly on the inner leaflet in healthy cells. Translocation of PS to the outer leaflet makes it available as a target for biological therapies. We examined PS translocation after radiosurgery in an animal model of brain arteriovenous malformation (AVM). An arteriovenous fistula was created by end-to-side anastomosis of the left external jugular vein to the common carotid artery in 6-week-old, male Sprague Dawley rats...
June 2017: Radiation Research
https://www.readbyqxmd.com/read/28369944/increasing-acetyl-coa-metabolism-attenuates-injury-and-alters-spinal-cord-lipid-content-in-mice-subjected-to-experimental-autoimmune-encephalomyelitis
#14
Amber C Chevalier, Thad A Rosenberger
Acetate supplementation increases brain acetyl-CoA metabolism, alters histone and non-histone protein acetylation, increases brain energy reserves, and is anti-inflammatory and neuroprotective in rat models of neuroinflammation and neuroborreliosis. To determine the impact acetate supplementation has on a mouse model of multiple sclerosis, we quantified the effect treatment had on injury progression, spinal cord lipid content, phospholipase levels, and myelin structure in mice subjected to experimental autoimmune encephalomyelitis (EAE)...
June 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28235468/lipid-mapping-of-the-rat-brain-for-models-of-disease
#15
J Martínez-Gardeazabal, E González de San Román, M Moreno-Rodríguez, A Llorente-Ovejero, I Manuel, R Rodríguez-Puertas
Lipids not only constitute the primary component of cellular membranes and contribute to metabolism but also serve as intracellular signaling molecules and bind to specific membrane receptors to control cell proliferation, growth and convey neuroprotection. Over the last several decades, the development of new analytical techniques, such as imaging mass spectrometry (IMS), has contributed to our understanding of their involvement in physiological and pathological conditions. IMS allows researchers to obtain a wide range of information about the spatial distribution and abundance of the different lipid molecules that is crucial to understand brain functions...
February 21, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28202633/regional-changes-in-cns-and-retinal-glycerophospholipid-profiles-with-age-a-molecular-blueprint
#16
Blake R Hopiavuori, Martin-Paul Agbaga, Richard S Brush, Michael T Sullivan, William E Sonntag, Robert E Anderson
We present here a quantitative molecular blueprint of the three major glycerophospholipid (GPL) classes, phosphatidylcholine (PC), phosphatidylserine (PS), and phosphatidylethanolamine (PE), in retina and six regions of the brain in C57Bl6 mice at 2, 10, and 26 months of age. We found an age-related increase in molecular species containing saturated and monoenoic FAs and an overall decrease in the longer-chain PUFA molecular species across brain regions, with loss of DHA-containing molecular species as the most consistent and dramatic finding...
April 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28167298/diabetes-alters-myelin-lipid-profile-in-rat-cerebral-cortex-protective-effects-of-dihydroprogesterone
#17
Gaia Cermenati, Silvia Giatti, Matteo Audano, Marzia Pesaresi, Roberto Spezzano, Donatella Caruso, Nico Mitro, Roberto Cosimo Melcangi
Due to the emerging association of diabetes with several psychiatric and neurodegenerative events, the evaluation of the effects of this pathology on the brain function has now a high priority in biomedical research. In particular, the effects of diabetes on myelin compartment have been poorly taken into consideration. To this purpose, we performed a deep lipidomic analysis of cortical myelin in the streptozotocin-induced diabetic rat model. In male rats three months of diabetes induced an extensive alterations in levels of phosphatidylcholines and phosphatidylethanolamines (the main species present in myelin membranes), plasmalogens as well as phosphatidylinositols and phosphatidylserines...
April 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28138026/preclinical-evaluation-of-sequential-combination-of-oncolytic-adenovirus-delta-24-rgd-and-phosphatidylserine-targeting-antibody-in-pancreatic-ductal-adenocarcinoma
#18
Bingbing Dai, David Roife, Ya'an Kang, Joy Gumin, Mayrim V Rios Perez, Xinqun Li, Michael Pratt, Rolf A Brekken, Juan Fueyo-Margareto, Frederick F Lang, Jason B Fleming
Delta-24-RGD (DNX-2401) is a conditional replication-competent oncolytic virus engineered to preferentially replicate in and lyse tumor cells with abnormality of p16/RB/E2F pathway. In a phase I clinical trial, Delta-24-RGD has shown favorable safety profile and promising clinical efficacy in brain tumor, which prompted us to evaluate its anticancer activity in pancreatic ductal adenocarcinoma (PDAC), which also has high frequency of homozygous deletion and promoter methylation of CDKN2A encoding the p16 protein...
April 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28029283/evaluation-of-procoagulant-tissue-factor-expression-in-canine-hemangiosarcoma-cell-lines
#19
Lauren E Witter, Erika J Gruber, Fabian Z X Lean, Tracy Stokol
OBJECTIVE To evaluate expression of procoagulant tissue factor (TF) by canine hemangiosarcoma cells in vitro. SAMPLES 4 canine hemangiosarcoma cell lines (SB-HSA [mouse-passaged cutaneous tumor], Emma [primary metastatic brain tumor], and Frog and Dal-1 [primary splenic tumors]) and 1 nonneoplastic canine endothelial cell line (CnAoEC). PROCEDURES TF mRNA and TF antigen expression were evaluated by quantitative real-time PCR assay and flow cytometry, respectively. Thrombin generation was measured in canine plasma and in coagulation factor-replete or specific coagulation factor-deficient human plasma by calibrated automated thrombography...
January 2017: American Journal of Veterinary Research
https://www.readbyqxmd.com/read/28028735/mapping-of-surface-exposed-epitopes-of-in-vitro-and-in-vivo-aggregated-species-of-alpha-synuclein
#20
Leire Almandoz-Gil, Veronica Lindström, Jessica Sigvardson, Philipp J Kahle, Lars Lannfelt, Martin Ingelsson, Joakim Bergström
Aggregated alpha-synuclein is the main component of Lewy bodies, intraneuronal deposits observed in Parkinson's disease and dementia with Lewy bodies. The objective of the study was to identify surface-exposed epitopes of alpha-synuclein in vitro and in vivo formed aggregates. Polyclonal immunoglobulin Y antibodies were raised against short linear peptides of the alpha-synuclein molecule. An epitope in the N-terminal region (1-10) and all C-terminal epitopes (90-140) were found to be exposed in an indirect enzyme-linked immunosorbent assay (ELISA) using recombinant monomeric, oligomeric, and fibrillar alpha-synuclein...
December 27, 2016: Cellular and Molecular Neurobiology
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