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https://www.readbyqxmd.com/read/28343126/pi3k-signaling-in-cancer-beyond-akt
#1
REVIEW
Evan C Lien, Christian C Dibble, Alex Toker
The phosphoinositide 3-kinase (PI3K) signaling pathway is one of the most frequently altered pathways in human cancer and has a critical role in driving tumor initiation and progression. Although PI3K and its lipid product phosphatidylinositol-3,4,5-trisphosphate (PIP3) have been shown to activate multiple downstream signaling proteins, the vast majority of studies have focused on the protein kinase AKT as the dominant effector of PI3K signaling. However, recent studies have demonstrated many contexts under which other PIP3-dependent signaling proteins critically contribute to cancer progression, illustrating the importance of understanding AKT-independent signaling downstream of PI3K...
March 23, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28342860/functional-characterization-of-lysophosphatidic-acid-receptor-1-mutants-identified-in-rat-cancer-tissues
#2
Shoichi Ishii, Toshifumi Tsujiuchi, Nobuyuki Fukushima
Lysophosphatidic acid (LPA), an extracellular lipid mediator, exerts various cellular effects through activation of LPA receptors, LPA1-LPA6, in many types of cells including cancer cells. We recently found several missense mutations of Lpar1 in rat cancer tissues. One of these mutations is located at the extracellular tip of the seventh transmembrane domain of LPA1, and another three mutations are found within the NPXXY motif in the seventh transmembrane domain. These mutants are designated F295S LPA1 and P308S, I310T, and Y311H LPA1, respectively...
March 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28342847/na-k-atpase-interaction-with-methylglyoxal-as-reactive-metabolic-side-product
#3
Marika Svrckova, Martina Zatloukalova, Petra Dvorakova, Dominika Coufalova, David Novak, Lenka Hernychova, Jan Vacek
Proteins are subject to oxidative modification and the formation of adducts with a broad spectrum of reactive species via enzymatic and non-enzymatic mechanisms. Here we report that in vitro non-enzymatic methylglyoxal (MGO) binding causes the inhibition and formation of MGO advanced glycation end-products (MAGEs) in Na(+)/K(+)-ATPase (NKA). Concretely, MGO adducts with NKA amino acid residues (mainly Arg) and N(ε)-(carboxymethyl)lysine (CML) formation were found. MGO is not only an inhibitor for solubilized NKA (IC50 = 91±16 μM), but also for reconstituted NKA in the lipid bilayer environment, which was clearly demonstrated using a DPPC/DPPE liposome model in the presence or absence of the NKA-selective inhibitor ouabain...
March 22, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28342784/inositol-phosphate-multikinase-dependent-transcriptional-control
#4
Ace J Hatch, Audrey R Odom, John D York
Production of lipid-derived inositol phosphates including IP4 and IP5 is an evolutionarily conserved process essential for cellular adaptive responses that is dependent on both phospholipase C and the inositol phosphate multikinase Ipk2 (also known as Arg82 and IPMK). Studies of Ipk2, along with Arg82 prior to demonstrating its IP kinase activity, have provided an important link between control of gene expression and IP metabolism as both kinase dependent and independent functions are required for proper transcriptional complex function that enables cellular adaptation in response to extracellular queues such as nutrient availability...
March 21, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/28342757/role-of-enzymatic-free-radical-scavengers-in-management-of-oxidative-stress-and-autoimmune-disorders
#5
REVIEW
Shikha Srivastava, Deependra Singh, Satish Patel, Manju R Singh
Autoimmune disorders are distinct with over production and accumulation of free radicals due to its undisclosed genesis. The cause of numerous disorders as cancer, arthritis, psoriasis, diabetes, alzheimer's, cardiovascular disease, Parkinson's, respiratory distress syndrome, colitis, crohn's, pulmonary fibrosis, obesity and ageing have been associated with immune dysfunction and oxidative stress. In an oxidative stress, reactive oxygen species generally provoke the series of oxidation at cellular level. The buildup of free radicals in turn triggers various inflammatory cells causing release of various inflammatory interleukins, cytokines, chemokines, and tumor necrosis factors which mediate signal transduction and transcription pathways as nuclear factor- kappa B (NF-κB), signal transducer and activator of transcription 3 (STAT3), hypoxia-inducible factor-1 (HIF-1α) and nuclear factor-erythroid 2-related factor (Nrf2)...
March 22, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28342710/emerging-role-of-chemoprotective-agents-in-the-dynamic-shaping-of-plasma-membrane-organization
#6
REVIEW
Natividad R Fuentes, Michael L Salinas, Eunjoo Kim, Robert S Chapkin
In the context of an organism, epithelial cells by nature are designed to be the defining barrier between self and the outside world. This is especially true for the epithelial cells that form the lining of the digestive tract, which absorb nutrients and serve as a barrier against harmful substances. These cells are constantly bathed by a complex mixture of endogenous (bile acids, mucus, microbial metabolites) and exogenous (food, nutrients, drugs) bioactive compounds. From a cell biology perspective, this type of exposure would directly impact the plasma membrane, which consists of a myriad of complex lipids and proteins...
March 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28339575/histaminergic-neurotransmission-as-a-gateway-for-the-cognitive-effect-of-oleoylethanolamide-in-contextual-fear-conditioning
#7
Gustavo Provensi, Roberta Fabbri, Leonardo Munari, Alessia Costa, Elisabetta Baldi, Corrado Bucherelli, Patrizio Blandina, Maria Beatrice Passani
Background: The integrity of the brain histaminergic system is necessary for the unfolding of homeostatic and cognitive processes through the recruitment of alternative circuits with distinct temporal patterns. We recently demonstrated that the fat-sensing lipid mediator oleoylethanolamide indirectly activates histaminergic neurons to exerts its hypophagic effects. The present experiments investigated whether histaminergic neurotransmission is necessary also for the modulation of emotional memory induced by oleoylethanolamide in a contextual fear conditioning paradigm...
January 19, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28338624/nerve-growth-factor-signaling-from-membrane-microdomains-to-the-nucleus-differential-regulation-by-caveolins
#8
Ambre Spencer, Lingli Yu, Vincent Guili, Florie Reynaud, Yindi Ding, Ji Ma, Jérôme Jullien, David Koubi, Emmanuel Gauthier, David Cluet, Julien Falk, Valérie Castellani, Chonggang Yuan, Brian B Rudkin
Membrane microdomains or "lipid rafts" have emerged as essential functional modules of the cell, critical for the regulation of growth factor receptor-mediated responses. Herein we describe the dichotomy between caveolin-1 and caveolin-2, structural and regulatory components of microdomains, in modulating proliferation and differentiation. Caveolin-2 potentiates while caveolin-1 inhibits nerve growth factor (NGF) signaling and subsequent cell differentiation. Caveolin-2 does not appear to impair NGF receptor trafficking but elicits prolonged and stronger activation of MAPK (mitogen-activated protein kinase), Rsk2 (ribosomal protein S6 kinase 2), and CREB (cAMP response element binding protein)...
March 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28337749/branched-i%C3%A2-antigens-on-leukemia-cells-enhanced-sensitivity-against-natural-killer-cell-cytotoxicity-through-affecting-the-target-effector-interaction
#9
Yen-Hua Lee, Yi-Jen Liao, Chin-Han Huang, Fu-Ling Chang, Ting-Hsi Fan, Yuh-Ching Twu
BACKGROUND: The aberrant glycosylation on proteins and lipids has been implicated in malignant transformations for promoting the tumorigenesis, metastasis, and evasion from the host immunity. The I-branching β-1,6-N-acetylglucosaminyltransferase, converting the straight i to branched I histo-blood group antigens, reportedly could influence the migration, invasion, and metastasis of solid tumors. STUDY DESIGN AND METHODS: We first chose the highly cytotoxic natural killer (NK)-92MI cells as effector against leukemia for this cell line has been used in several clinical trials...
March 24, 2017: Transfusion
https://www.readbyqxmd.com/read/28337522/pre-symptomatic-autoimmunity-in-rheumatoid-arthritis-when-does-the-disease-start
#10
REVIEW
Alexander Tracy, Christopher D Buckley, Karim Raza
It is well recognised that a state of autoimmunity, in which immunological tolerance is broken, precedes the development of symptoms in the majority of patients with rheumatoid arthritis (RA). For individuals who will later develop seropositive disease, this manifests as autoantibodies directed against proteins that have undergone specific post-translational modifications. There is evidence that the induction of this autoantibody response occurs at peripheral extra-articular mucosal sites, such as the periodontium and lung...
March 23, 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/28336574/switching-head-group-selectivity-in-mammalian-sphingolipid-biosynthesis-by-active-site-engineering-of-sphingomyelin-synthases
#11
Matthijs Kol, Radhakrishnan Panatala, Mirjana Nordmann, Leoni Swart, Leonie Van Suijlekom, Birol Cabukusta, Angelika Hilderink, Tanja Gabrietz, John G M Mina, Pentti Somerharju, Sergei Korneev, Fikadu G Tafesse, Joost C M Holthuis
Sphingomyelin (SM) is a fundamental component of mammalian cell membranes that contributes to mechanical stability, signaling and sorting. Its production involves the transfer of phosphocholine from phosphatidylcholine onto ceramide, a reaction catalyzed by SM synthase SMS1 in the Golgi and SMS2 at the plasma membrane. Mammalian cells also synthesize trace amounts of the SM analog ceramide phosphoethanolamine (CPE), but the physiological relevance of CPE production is unclear. Previous work revealed that SMS2 is a bifunctional enzyme producing both SM and CPE whereas a closely related enzyme, SMSr/SAMD8, acts as a monofunctional CPE synthase in the ER...
March 23, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28336528/platelet-cd36-promotes-thrombosis-by-activating-redox-sensor-erk5-in-hyperlipidemic-conditions
#12
Moua Yang, Brian C Cooley, Wei Li, Yiliang Chen, Jeannette Vasquez-Vivar, Na'il O Scoggins, Scott J Cameron, Craig N Morrell, Roy L Silverstein
Atherothrombosis is a process mediated by dysregulated platelet activation that can cause life-threatening complications and is the leading cause of death by cardiovascular disease. Platelet reactivity in hyperlipidemic conditions is enhanced when platelet scavenger receptor CD36 recognizes oxidized lipids in LDL particles, a process which induces an overt prothrombotic phenotype. The mechanisms by which CD36 promotes platelet activation and thrombosis remain incompletely defined. In this study, we identify a mechanism for CD36 to promote thrombosis by increasing activation of MAP kinase ERK5, a protein kinase known to be exquisitely sensitive to redox stress, through a signaling pathway requiring Src kinases, NADPH oxidase, superoxide radical anion and hydrogen peroxide...
March 23, 2017: Blood
https://www.readbyqxmd.com/read/28336294/palmitate-mediated-diacylglycerol-accumulation-causes-endoplasmic-reticulum-stress-plin2-degradation-and-cell-death-in-h9c2-cardiomyoblasts
#13
Ali Akoumi, Taha Haffar, Maria Mousterji, Robert Scott Kiss, Nicolas Bousette
We have previously shown that palmitate causes ER stress in primary cardiomyocytes and this was associated with a diffuse lipid staining histology. In contrast, oleate, which was non-toxic, led to the formation of abundant, clearly delineated lipid droplets. The aberrant lipid histology in palmitate treated cells led us to hypothesize that perhaps there was an impairment in lipid droplet formation, which could lead to accumulation of lipids in the ER and consequent ER stress. To test this hypothesis we treated H9C2s (a cardiomyoblast cell line) with either 300µM oleate or palmitate for 8h...
March 21, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28335781/tailored-design-of-nkt-stimulatory-glycolipids-for-polarization-of-immune-responses
#14
REVIEW
Jung-Tung Hung, Jing-Rong Huang, Alice L Yu
Natural killer T (NKT) cell is a distinct population of T lymphocytes that can rapidly release massive amount of Th1 and Th2 cytokines upon the engagement of their T cell receptor with glycolipids presented by CD1d. The secreted cytokines can promote cell-mediated immunity to kill tumor cells and intracellular pathogens, or suppress autoreactive immune cells in autoimmune diseases. Thus, NKT cell is an attractive target for developing new therapeutics to manipulate immune system. The best-known glycolipid to activate NKT cells is α-galactosylceramide (α-GalCer), which has been used as a prototype for designing new NKT stimulatory glycolipids...
March 23, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28335584/atrap-expression-in-brown-adipose-tissue-does-not-influence-the-development-of-diet-induced-metabolic-disorders-in-mice
#15
Kohji Ohki, Hiromichi Wakui, Kengo Azushima, Kazushi Uneda, Sona Haku, Ryu Kobayashi, Kotaro Haruhara, Sho Kinguchi, Miyuki Matsuda, Masato Ohsawa, Akinobu Maeda, Shintaro Minegishi, Tomoaki Ishigami, Yoshiyuki Toya, Akio Yamashita, Satoshi Umemura, Kouichi Tamura
Activation of tissue renin-angiotensin system (RAS), mainly mediated by an angiotensin II (Ang II) type 1 receptor (AT1R), plays an important role in the development of obesity-related metabolic disorders. We have shown that AT1R-associated protein (ATRAP), a specific binding protein of AT1R, functions as an endogenous inhibitor to prevent excessive activation of tissue RAS. In the present study, we newly generated ATRAP/Agtrap-floxed (ATRAP(fl/fl)) mice and adipose tissue-specific ATRAP downregulated (ATRAP(adipoq)) mice by the Cre/loxP system using Adipoq-Cre...
March 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28334537/multivalency-effect-of-tat-peptide-functionalized-nanoparticle-in-cellular-endocytosis-and-subcellular-trafficking
#16
Nikhil R Jana, Chumki Dalal
Although trans-activating transcription (TAT)-peptide functionalized nanoparticle/polymer/liposome is widely used for cellular transfection applications, the multivalency (number of attached peptide per particle) effect on cell uptake mechanism and subcellular targeting performance is largely unexplored. Here we show that multivalency of nanoparticle controls the cellular interaction, cellular entry/exit mechanism and subcellular targeting performance. We have synthesized TAT peptide functionalized quantum dot (QD) of 30-35 nm hydrodynamic diameter with varied multivalency from 10 to 75 (e...
March 23, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28334008/low-sphingosine-1-phosphate-plasma-levels-are-predictive-for-increased-mortality-in-patients-with-liver-cirrhosis
#17
Susen Becker, Benedict Kinny-Köster, Michael Bartels, Markus Scholz, Daniel Seehofer, Thomas Berg, Cornelius Engelmann, Joachim Thiery, Uta Ceglarek, Thorsten Kaiser
BACKGROUND & AIM: The association of circulating sphingosine-1-phosphate (S1P), a bioactive lipid involved in various cellular processes, and related metabolites such as sphinganine-1-phosphate (SA1P) and sphingosine (SPH) with mortality in patients with end-stage liver disease is investigated in the presented study. S1P as a bioactive lipid mediator, is involved in several cellular processes, however, in end-stage liver disease its role is not understood. METHODS: The study cohort consisted of 95 patients with end-stage liver disease and available information on one-year outcome...
2017: PloS One
https://www.readbyqxmd.com/read/28333068/effects-of-reactive-oxygen-species-on-tubular-transport-along-the-nephron
#18
REVIEW
Agustin Gonzalez-Vicente, Jeffrey L Garvin
Reactive oxygen species (ROS) are oxygen-containing molecules naturally occurring in both inorganic and biological chemical systems. Due to their high reactivity and potentially damaging effects to biomolecules, cells express a battery of enzymes to rapidly metabolize them to innocuous intermediaries. Initially, ROS were considered by biologists as dangerous byproducts of respiration capable of causing oxidative stress, a condition in which overproduction of ROS leads to a reduction in protective molecules and enzymes and consequent damage to lipids, proteins, and DNA...
March 23, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28330814/ala-pdt-suppressing-the-cell-growth-and-reducing-the-lipogenesis-in-human-sz95-sebocytes-by-mtor-signaling-pathway-in-vitro
#19
Jiang Tuo, Qianqian Wang, Ye Liu, Ying Ma, Li Ma, Jiayi Ying, Chengfeng Zhang, Leihong Xiang
BACKGROUND: 5-Aminolevulinic acid mediated -photodynamic therapy (ALA-PDT) is known to be effective in treating acne vulgaris and other sebaceous gland-related diseases. However, thetherapeutic mechanisms of ALA-PDT still remain undetermined. In this study, we aimed to investigate theeffects and mechanisms of ALA-PDTon the cell growth and lipogenesis of human SZ95 sebocytes. MATERIAL AND METHODS: Human SZ95 sebocytes were treated with different concentration of ALA-PDT...
March 19, 2017: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/28330813/atp-binding-cassette-transporter-a1-deficiency-in-human-induced-pluripotent-stem-cell-derived-hepatocytes-abrogates-hdl-biogenesis-and-enhances-triglyceride-secretion
#20
Xin Bi, Evanthia E Pashos, Marina Cuchel, Nicholas N Lyssenko, Mayda Hernandez, Antonino Picataggi, James McParland, Wenli Yang, Ying Liu, Ruilan Yan, Christopher Yu, Stephanie L DerOhannessian, Michael C Phillips, Edward E Morrisey, Stephen A Duncan, Daniel J Rader
Despite the recognized role of the ATP-binding Cassette Transporter A1 (ABCA1) in high-density lipoprotein (HDL) metabolism, our understanding of ABCA1 deficiency in human hepatocytes is limited. To define the functional effects of human hepatocyte ABCA1 deficiency, we generated induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells (HLCs) from Tangier disease (TD) and matched control subjects. Control HLCs exhibited robust cholesterol efflux to apolipoprotein A-I (apoA-I) and formed nascent HDL particles...
March 14, 2017: EBioMedicine
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