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https://www.readbyqxmd.com/read/28811617/cell-surface-binding-uptaking-and-anticancer-activity-of-l-k6-a-lysine-leucine-rich-peptide-on-human-breast-cancer-mcf-7-cells
#1
Che Wang, Shaodan Dong, Lin Zhang, Ying Zhao, Lili Huang, Xiange Gong, He Wang, Dejing Shang
Cell surface binding and internalization are critical for the specific targeting and biofunctions of some cationic antimicrobial peptides (CAPs) with anticancer activities. However, the detailed cellular process for CAPs interacting with cancer cells and the exact molecular basis for their anticancer effects are still far from being fully understood. In the present study, we examined the cell surface binding, uptaking and anti-cancer activity of L-K6, a lysine/leucine-rich CAP, in human MCF-7 breast cancer cells...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808400/induction-of-apoptosis-and-cell-cycle-arrest-by-flavokawain-c-on-ht-29-human-colon-adenocarcinoma-via-enhancement-of-reactive-oxygen-species-generation-upregulation-of-p21-p27-and-gadd153-and-inactivation-of-inhibitor-of-apoptosis-proteins
#2
Chung-Weng Phang, Saiful Anuar Karsani, Sri Nurestri Abd Malek
Chalcones have been shown to exhibit anti-cancer properties by targeting multiple molecular pathways. It was, therefore, of interest to investigate flavokawain C (FKC), a naturally occurring chalcone, which can be isolated from Kava (Piper methysticum Forst) root extract. The aim of this study was to investigate the inhibitory effect of FKC on the growth of HT-29 cells and its underlying mechanism of action. Cell viability of HT-29 cells was assessed by Sulforhodamine B assay after FKC treatment. Induction of apoptosis was examined by established morphological and biochemical assays...
July 2017: Pharmacognosy Magazine
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
#3
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/28804842/flow-cytometry-protocols-for-assessment-of-platelet-function-in-whole-blood
#4
Leonardo Pasalic, Gabrielle J Pennings, David Connor, Heather Campbell, Leonard Kritharides, Vivien M Chen
Flow cytometry is a powerful tool for rapid evaluation of multiple functional properties of large numbers of platelets in whole blood. In the following chapter, we provide a number of flow cytometry-based protocols broadly aimed at (1) assessment of constitutively expressed platelet membrane receptors to diagnose inherited platelet bleeding disorders and (2) investigation of basal and agonist-induced platelet functional responses including generation of platelet-leukocyte aggregates, alpha and dense granule release, calcium flux, and phosphatidylserine exposure...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28803650/lipid-determination-in-bone-marrow-and-mineralized-bone-tissue-from-sample-preparation-to-improved-high-performance-thin-layer-and-liquid-chromatographic-approaches
#5
Alexandrine During
In view of their key roles in the bone physiology (e.g., in the biomineralization process) and their potential implication in bone pathologies, an approach to study lipids in situ is needed. The aim of the present paper is to propose an original procedure to characterize lipids in both bone marrow (BM) and mineralized tissue (MT) compartments, taking into consideration sample preparation, lipid extraction and analytical issues, when using small sample size (≤ 0.5g of rat femurs). The potential contamination of the MT by marrow lipids and the poor accessibility of certain lipids from the MT - two major issues in bone handling - were taking care, respectively by performing two cleaning steps after BM removal and by adding a demineralization step to the overall lipid extraction protocol...
August 3, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28802697/the-insertion-of-polybia-mp1-into-phospholipid-monolayers-is-regulated-by-its-anionic-nature-and-phase-state
#6
Dayane S Alvares, Natalia Wilke, João Ruggiero Neto, Maria Laura Fanani
Polybia-MP1 or simply MP1 (IDWKKLLDAAKQIL-NH2) is a peptide with broad-spectrum bactericidal activity and a strong inhibitory effect against cancer cells. The aim of this work was to evaluate the effect of biophysical properties such as membrane texture and film thickness on MP1 interaction with neutral and anionic lipid membranes. For this purpose, we first explored the peptide's surface behavior. MP1 showed high surface activity, adsorbing onto bare air/aqueous interfaces up to higher surface pressures than the collapse pressure of MP1 Langmuir films...
August 9, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28802228/mtdh-and-map3k1-are-direct-targets-of-apoptosis-regulating-mirnas-in-colorectal-carcinoma
#7
Sohair M Salem, Ahmed R Hamed, Rehab M Mosaad
Artificially designed miRNAs mimics and inhibitors that specifically target known oncogenes have attracted significant research attention. Herein, we aimed to explore whether MIR-375, MIR-145, and MIR-224 are involved in induction of apoptosis of CRC cells by regulating apoptosis-mediating genes MTDH, MAP3K1, PDK1, BAX, and BCL-XL. MTT assay was used to assess cell growth. Apoptosis was determined in terms of caspase activity measurement and phosphatidylserine detection using annexin V staining by flow cytometry...
August 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28801460/multiplexed-silicon-photonic-sensor-arrays-enable-facile-characterization-of-coagulation-protein-binding-to-nanodiscs-with-variable-lipid-content
#8
Ellen M Muehl, Joshua M Gajsiewicz, Sara M Medfisch, Zachary S B Wiersma, James H Morrissey, Ryan C Bailey
Interactions of soluble proteins with the cell membrane are critical within the blood coagulation cascade. Of particular interest are the interactions of γ-carboxyglutamic acid-rich (GLA) domain-containing clotting proteins with lipids. Variability among conventional analytical methods presents challenges for comparing clotting protein-lipid interactions. Most previous studies have investigated only a single clotting protein and lipid composition and have yielded widely different binding constants. Herein, we demonstrate that a combination of lipid bilayer Nanodiscs and a multiplexed silicon photonic analysis technology enables high-throughput probing of many protein-lipid interactions among blood-clotting proteins...
August 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28793293/triggering-of-eryptosis-the-suicidal-erythrocyte-death-by-mammalian-target-of-rapamycin-mtor-inhibitor-temsirolimus
#9
Abdulla Al Mamun Bhuyan, Hang Cao, Florian Lang
BACKGROUND/AIMS: The mammalian target of rapamycin (mTOR) inhibitor temsirolimus is utilized for the treatment of malignancy. Temsirolimus is at least in part effective by triggering suicidal tumor cell death. The most common side effect of temsirolimus treatment is anemia. At least in theory, the anemia following temsirolimus treatment could result from stimulation of eryptosis, the suicidal erythrocyte death. Hallmarks of eryptosis include cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface...
July 24, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28793283/trifluoperazine-induced-suicidal-erythrocyte-death-and-s-nitrosylation-inhibition-reversed-by-the-nitric-oxide-donor-sodium-nitroprusside
#10
Mehrdad Ghashghaeinia, Mauro Carlos Wesseling, Elena Ramos, Polina Petkova-Kirova, Sabrina Waibel, Elisabeth Lang, Rosi Bissinger, Kossai Alzoubi, Baerbel Edelmann, Zohreh Hosseinzadeh, Peter Dreischer, Azam Shahvaroughi-Farahani, Ulrich Mrowietz, Martin Köberle, Lars Kaestner, Ingolf Bernhardt, Antonio Martínez-Ruiz, Thomas Wieder, Florian Lang
BACKGROUND AND PURPOSE: The high potency antipsychotic drug trifluoperazine (10-[3-(4-methyl-1-piperazinyl)-propyl]-2-(trifluoromethyl)-(10)H-phenothiazine dihydrochloride; TFP) may either counteract or promote suicidal cell death or apoptosis. Similar to apoptosis, erythrocytes may enter eryptosis, characterized by phosphatidylserine exposure at the cell surface and cell shrinkage. Eryptosis can be stimulated by an increase in cytoplasmic Ca2+ concentration ([Ca2+]i) and inhibited by nitric oxide (NO)...
August 9, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28792888/structural-basis-for-interdomain-communication-in-ship2-providing-high-phosphatase-activity
#11
Johanne Le Coq, Marta Camacho-Artacho, José Vicente Velázquez, Clara M Santiveri, Luis Heredia Gallego, Ramón Campos-Olivas, Nicole Dölker, Daniel Lietha
SH2-containing-inositol-5-phosphatases (SHIPs) dephosphorylate the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3) and play important roles in regulating the PI3K/Akt pathway in physiology and disease. Aiming to uncover interdomain regulatory mechanisms in SHIP2, we determined crystal structures containing the 5-phosphatase and a proximal region adopting a C2 fold. This reveals an extensive interface between the two domains, which results in significant structural changes in the phosphatase domain...
August 9, 2017: ELife
https://www.readbyqxmd.com/read/28782177/lipid-specificity-of-the-membrane-binding-domain-of-coagulation-factor-x
#12
Melanie P Muller, Yan Wang, James H Morrissey, Emad Tajkhorshid
BACKGROUND: Factor X (FX) binds to cell membranes in a highly phospholipid-dependent manner and, in complex with tissue factor and factor VIIa (FVIIa), initiates the clotting cascade. Experimental information concerning the membrane-bound structure of FX with atomic resolution has remained elusive due to the fluid nature of cellular membranes. FX is known to bind preferentially to phosphatidylserine (PS). OBJECTIVES: To develop the first membrane-bound model of FX-GLA domain to PS at atomic level, and to identify PS-specific binding sites of FX-GLA domain...
August 7, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28768810/mouse-macrophages-show-different-requirements-for-phosphatidylserine-receptor-tim4-in-efferocytosis
#13
Yuichi Yanagihashi, Katsumori Segawa, Ryota Maeda, Yo-Ichi Nabeshima, Shigekazu Nagata
Protein S (ProS) and growth arrest-specific 6 (Gas6) bind to phosphatidylserine (PtdSer) and induce efferocytosis upon binding TAM-family receptors (Tyro3, Axl, and Mer). Here, we produced mouse ProS, Gas6, and TAM-receptor extracellular region fused to IgG fragment crystallizable region in HEK293T cells. ProS and Gas6 bound Ca(2+) dependently to PtdSer (Kd 20-40 nM), Mer, and Tyro3 (Kd 15-50 nM). Gas6 bound Axl strongly (Kd < 1.0 nM), but ProS did not bind Axl. Using NIH 3T3-based cell lines expressing a single TAM receptor, we showed that TAM-mediated efferocytosis was determined by the receptor-binding ability of ProS and Gas6...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28764904/photosensitized-methyl-paraben-induces-apoptosis-via-caspase-dependent-pathway-under-ambient-uvb-exposure-in-human-skin-cells
#14
Divya Dubey, Deepti Chopra, Jyoti Singh, Ajeet K Srivastav, Smita Kumari, Ankit Verma, Ratan Singh Ray
Methyl paraben (MP), is a widely used preservative in pharmaceutical, food and cosmetic products. Its molecular mechanism under ambient ultraviolet radiation is not well understood. We investigated photosensitizing mechanism of MP under ambient UVB (0.6 mW/cm(2)) intensity. MP showed dose dependent decrease in cell viability of human keratinocyte cell line (HaCaT) by MTT and NRU assays. Study showed 40% reduction in antimicrobial activity of UVB irradiated MP through E. coli culture. Photosensitized MP (25 μg/ml) significantly enhanced lipid peroxidation, intracellular ROS generation and disrupted mitochondrial membrane integrity...
July 29, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28763330/a-phase-i-clinical-trial-of-the-phosphatidylserine-targeting-antibody-bavituximab-in-combination-with-radiation-therapy-and-capecitabine-in-the-preoperative-treatment-of-rectal-adenocarcinoma
#15
Jeffrey Meyer, Yull Arriaga, Joselin Anandam, Sirisha Karri, Samira Syed, Udit Verma, Abier Abdelnaby, Grace Raja, Ying Dong, Muhammad Beg, Glen Balch
OBJECTIVES: There is interest in improving the tumoricidal effects of preoperative radiotherapy for rectal carcinoma by studying new radiosensitizers. The safety and toxicity profile of these combination regimens needs rigorous clinical evaluation. The primary objective of this study was to evaluate the toxicity of combining bavituximab, an antibody that targets exposed phosphatidylserine, with capecitabine and radiation therapy. MATERIALS AND METHODS: Patients with stage II or III rectal adenocarcinoma were enrolled on a phase I study combining radiation therapy, capecitabine, and bavituximab...
July 31, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28760485/phospholipid-class-specific-brain-enrichment-in-response-to-lysophosphatidylcholine-docosahexaenoic-acid-infusion
#16
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...
July 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28758971/tricetin-induces-apoptosis-of-human-leukemic-hl-60-cells-through-a-reactive-oxygen-species-mediated-c-jun-n-terminal-kinase-activation-pathway
#17
Ming-Hsien Chien, Jyh-Ming Chow, Wei-Jiunn Lee, Hui-Yu Chen, Peng Tan, Yu-Ching Wen, Yung-Wei Lin, Pei-Ching Hsiao, Shun-Fa Yang
Tricetin is a dietary flavonoid with cytostatic properties and antimetastatic activities in various solid tumors. The anticancer effect of tricetin in nonsolid tumors remains unclear. Herein, the molecular mechanisms by which tricetin exerts its anticancer effects on acute myeloid leukemia (AML) cells were investigated. Results showed that tricetin inhibited cell viability in various types of AML cell lines. Tricetin induced morphological features of apoptosis such as chromatin condensation and phosphatidylserine (PS) externalization, and significantly activated proapoptotic signaling including caspase-8, -9, and -3 activation and poly(ADP-ribose) polymerase (PARP) cleavage in HL-60 AML cells...
July 31, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28758160/sphingomyelin-encrypts-tissue-factor-atp-induced-activation-of-a-smase-leads-to-tissue-factor-decryption-and-microvesicle-shedding
#18
Jue Wang, Usha R Pendurthi, L Vijaya Mohan Rao
A majority of tissue factor (TF) on cell surfaces exists in an encrypted state with minimal to no procoagulant activity. At present, it is unclear whether limited availability of phosphatidylserine (PS) and/or a specific membrane lipid in the outer leaflet of the plasma membrane contributes to TF encryption. Sphingomyelin (SM) is a major phospholipid in the outer leaflet, and SM metabolism is shown to be altered in many disease settings that cause thrombotic disorders. The present study is carried out to investigate the effect of SM metabolism on TF activity and TF(+) microvesicles (MVs) release...
May 23, 2017: Blood Advances
https://www.readbyqxmd.com/read/28754800/frontline-science-tim-3-mediated-dysfunctional-engulfment-of-apoptotic-cells-in-sle
#19
Di Zhao, Min Guo, Bing Liu, Qinghai Lin, Tingting Xie, Qianqian Zhang, Xiaoxia Jia, Qiang Shu, Xiaohong Liang, Lifen Gao, Chunhong Ma
T cell Ig and mucin domain-containing molecule 3 (Tim-3) has been found to play important roles in autoimmune diseases, but whether Tim-3-mediated engulfment of apoptotic cells is involved in systemic lupus erythematosus (SLE) remains to be elucidated. In this study, we verified the role of human Tim-3 (hTim-3) as the receptor of phosphatidylserine (PS) in human embryonic kidney (HEK)293 cells, which initiated the engulfment of apoptotic cells. Both IgV and the mucin domain of Tim-3 were crucial in the phagocytosis of apoptotic cells, and there existed the key cytoplasmic domain for signal transduction...
July 28, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28753886/distinct-lipidomic-landscapes-associated-with-clinical-stages-of-urothelial-cancer-of-the-bladder
#20
Danthasinghe Waduge Badrajee Piyarathna, Thekkelnaycke M Rajendiran, Vasanta Putluri, Venkatrao Vantaku, Tanu Soni, Friedrich-Carl von Rundstedt, Sri Ramya Donepudi, Feng Jin, Suman Maity, Chandrashekar R Ambati, Jianrong Dong, Daniel Gödde, Stephan Roth, Stephan Störkel, Stephan Degener, George Michailidis, Seth P Lerner, Subramaniam Pennathur, Yair Lotan, Cristian Coarfa, Arun Sreekumar, Nagireddy Putluri
BACKGROUND: The first global lipidomic profiles associated with urothelial cancer of the bladder (UCB) and its clinical stages associated with progression were identified. OBJECTIVE: To identify lipidomic signatures associated with survival and different clinical stages of UCB. DESIGN, SETTING, AND PARTICIPANTS: Pathologically confirmed 165 bladder-derived tissues (126 UCB, 39 benign adjacent or normal bladder tissues). UCB tissues included Ta (n=16), T1 (n=30), T2 (n=43), T3 (n=27), and T4 (n=9); lymphovascular invasion (LVI) positive (n=52) and negative (n=69); and lymph node status N0 (n=28), N1 (n=11), N2 (n=9), N3 (n=3), and Nx (n=75)...
April 20, 2017: European Urology Focus
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