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https://www.readbyqxmd.com/read/27898421/stimulation-of-erythrocyte-cell-membrane-scrambling-by-quinine
#1
Morena Mischitelli, Mohamed Jemaà, Mustafa Almasry, Caterina Faggio, Florian Lang
BACKGROUND/AIMS: The analkaloid drug quinine is utilized mainly for the chemoprophylaxis of malaria. The multiple side effects of quinine include hemolytic anemia and hemolytic uremic syndrome, disorders involving suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signaling contributing to stimulation of eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress, ceramide and D4476 sensitive casein kinase...
November 30, 2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27894925/dihydroceramide-desaturase-inhibitors-induce-autophagy-via-dihydroceramide-dependent-and-independent-mechanisms
#2
Mireia Casasampere, Yadira F Ordóñez, Josefina Casas, Gemma Fabrias
BACKGROUND: Autophagy consists on the delivery of cytoplasmic material and organelles to lysosomes for degradation. Research on autophagy is a growing field because deciphering the basic mechanisms of autophagy is key to understanding its role in health and disease, and to paving the way to discovering novel therapeutic strategies. Studies with chemotherapeutic drugs and pharmacological tools support a role for dihydroceramides as mediators of autophagy. However, their effect on the autophagy outcome (cell survival or death) is more controversial...
November 25, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27892898/the-role-of-adipose-tissue-and-excess-of-fatty-acids-in-the-induction-of-insulin-resistance-in-skeletal-muscle
#3
Agnieszka Błachnio-Zabielska, Sławomir Grycel, Marta Chacińska, Piotr Zabielski
Skeletal muscle is the main tissue responsible for insulin-stimulated glucose uptake. Consumption of a high-fat diet rich in saturated fats (HFD) and obesity are associated with accumulation of intramuscular lipids that leads to several disorders, e.g. insulin resistance (IRes) and type 2 diabetes (T2D). The mechanism underlying the induction of IRes is still unknown. It was speculated that accumulation of intramuscular triacylglycerols (TAG) is linked to induction of IRes. Now, research focuses on bioactive lipids: long-chain acyl-CoA (LCACoA), diacylglycerols (DAG) and ceramides (Cer)...
November 14, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/27891833/metabolomics-guided-insights-on-bariatric-surgery-versus-behavioral-interventions-for-weight-loss
#4
REVIEW
Sara Tulipani, Jules Griffin, Magali Palau-Rodriguez, Ximena Mora-Cubillos, Rosa M Bernal-Lopez, Francisco J Tinahones, Barbara E Corkey, Cristina Andres-Lacueva
OBJECTIVE: To review the metabolomic studies carried out so far to identify metabolic markers associated with surgical and dietary treatments for weight loss in subjects with obesity. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. RESULTS: Thirty-two studies successfully met the eligibility criteria. The metabolic adaptations shared by surgical and dietary interventions mirrored a state of starvation ketoacidosis (increase of circulating ketone bodies), an increase of acylcarnitines and fatty acid β-oxidation, a decrease of specific amino acids including branched-chain amino acids (BCAA) and (lyso)glycerophospholipids previously associated with obesity, and adipose tissue expansion...
December 2016: Obesity
https://www.readbyqxmd.com/read/27889774/stimulation-of-suicidal-erythrocyte-death-by-the-cdc25-inhibitor-nsc-95397
#5
Mohamed Jemaà, Morena Mischitelli, Myriam Fezai, Mustafa Almasry, Caterina Faggio, Florian Lang
BACKGROUND/AIMS: The CDC25B inhibitor NSC-95397 triggers apoptosis of tumor cells and is thus considered for the treatment of malignancy. The substance is effective in part by modification of gene expression. Similar to apoptosis of nucleated cells erythrocytes may undergo eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Eryptosis may be triggered by increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress, ceramide, as well as activation of protein kinases...
November 25, 2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27889758/stimulation-of-suicidal-erythrocyte-death-by-rottlerin
#6
Morena Mischitelli, Mohamed Jemaà, Mustafa Almasry, Caterina Faggio, Florian Lang
BACKGROUND/AIMS: The phytochemical polyphenol rottlerin is a potent activator of diverse Ca2+ -sensitive K+ channels. Those channels play a decisive role in the execution of eryptosis, the suicidal death of erythrocytes, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signaling involved in the stimulation of eryptosis includes increase of cytosolic Ca2+ activity ([Ca2+]i) and ceramide. The present study explored, whether rottlerin induces eryptosis and, if so, to test for the involvement of Ca2+ entry and ceramide...
November 25, 2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27888218/diverting-cert-mediated-ceramide-transport-to-mitochondria-triggers-bax-dependent-apoptosis
#7
Amrita Jain, Oliver Beutel, Katharina Ebell, Sergey Korneev, Joost C M Holthuis
A deregulation of ceramide biosynthesis in the ER is frequently linked to induction of mitochondrial apoptosis. While in vitro studies suggest that ceramides may initiate cell death by acting directly on mitochondria, their actual contribution to the apoptotic response in living cells is unclear. In here, we analyzed the consequences of targeting the biosynthetic flow of ceramides to mitochondria using a ceramide transfer protein equipped with an outer mitochondrial membrane anchor, mitoCERT. Cells expressing mitoCERT import ceramides into mitochondria and undergo Bax-dependent apoptosis...
November 25, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27882938/neutral-sphingomyelinase-smpd3-deficiency-disrupts-the-golgi-secretory-pathway-and-causes-growth-inhibition
#8
Wilhelm Stoffel, Ina Hammels, Bitta Jenke, Erika Binczek, Inga Schmidt-Soltau, Susanne Brodesser, Astrid Schauss, Julia Etich, Juliane Heilig, Frank Zaucke
Systemic loss of neutral sphingomyelinase (SMPD3) in mice leads to a novel form of systemic, juvenile hypoplasia (dwarfism). SMPD3 deficiency in mainly two growth regulating cell types contributes to the phenotype, in chondrocytes of skeletal growth zones to skeletal malformation and chondrodysplasia, and in hypothalamic neurosecretory neurons to systemic hypothalamus-pituitary-somatotropic hypoplasia. The unbiased smpd3-/- mouse mutant and derived smpd3-/- primary chondrocytes were instrumental in defining the enigmatic role underlying the systemic and cell autonomous role of SMPD3 in the Golgi compartment...
November 24, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27881717/localization-of-1-deoxysphingolipids-to-mitochondria-induces-mitochondrial-dysfunction
#9
Irina Alecu, Andrea Tedeschi, Natascha Behler, Klaus Wunderling, Christian Lamberz, Mario A R Lauterbach, Anne Gaebler, Daniela Ernst, Paul P Van Veldhoven, Ashraf Al-Amoudi, Eicke Latz, Alaa Othman, Lars Kuerschner, Thorsten Hornemann, Frank Bradke, Christoph Thiele, Anke Penno
1-Deoxysphingolipids (deoxySLs) are atypical sphingolipids that are elevated in the plasma of patients with type 2 diabetes and hereditary sensory and autonomic neuropathy type 1 (HSAN1). Clinically, diabetic neuropathy and HSAN1 are very similar, suggesting the involvement of deoxySLs in the pathology of both diseases. However, very little is known about the biology of these lipids and the underlying pathomechanism. We synthesized an alkyne analogue of 1-deoxysphinganine (doxSA), the metabolic precursor of all deoxySLs, to trace the metabolism and localization of deoxySLs...
November 23, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27881673/sortilin-1-modulates-hepatic-cholesterol-lipotoxicity-in-mice-via-functional-interaction-with-liver-carboxylesterase-1
#10
Jibiao Li, Yifeng Wang, David Matye, Hemantkumar Chavan, Partha Krishnamurthy, Feng Li, Tiangang Li
Liver plays a key role in cholesterol metabolism. Impaired hepatic cholesterol homeostasis causes intracellular free cholesterol accumulation and hepatocyte injury. Sortilin 1 (Sort1) is an intracellular lysosomal trafficking receptor that was recently identified by GWAS as a novel regulator of cholesterol metabolism in humans. Here we report that Sort1 deficiency protected against cholesterol accumulation-induced liver injury and inflammation in mice. Using LC-MS/MS based proteomics approach, we identified liver carboxyesterase 1 (CES1) as a novel Sort1 interacting protein...
November 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27880732/ceramide-activates-lysosomal-cathepsin-b-and-cathepsin-d-to-attenuate-autophagy-and-induces-er-stress-to-suppress-myeloid-derived-suppressor-cells
#11
Feiyan Liu, Xia Li, Chunwan Lu, Aiping Bai, Jacek Bielawski, Alicja Bielawska, Brendan Marshall, Patricia V Schoenlein, Iryna O Lebedyeva, Kebin Liu
Myeloid-derived suppressor cells (MDSCs) are immune suppressive cells that are hallmarks of human cancer. MDSCs inhibit cytotoxic T lymphocytes (CTLs) and NK cell functions to promote tumor immune escape and progression, and therefore are considered key targets in cancer immunotherapy. Recent studies determined a key role of the apoptosis pathways in tumor-induced MDSC homeostasis and it is known that ceramide plays a key role in regulation of mammalian cell apoptosis. In this study, we aimed to determine the efficacy and underlying molecular mechanism of ceramide in suppression of MDSCs...
November 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27876618/tlr4-nf-%C3%AE%C2%BAb-ceramide-signaling-contributes-to-ox-ldl-induced-calcification-of-human-vascular-smooth-muscle-cells
#12
Yan Song, Menglin Hou, Zhenlin Li, Chufan Luo, Jing-Song Ou, Huimin Yu, Jianyun Yan, Lihe Lu
Vascular calcification is a major feature of advanced atherosclerosis and highly associated with cardiovascular diseases. Oxidized low density lipoprotein (Ox-LDL) has been recognized as a critical risk factor for atherosclerosis and osteogenic differentiation of vascular smooth muscle cells (VSMCs). Previous studies have demonstrated that toll like receptor 4 (TLR4) is highly expressed in atherosclerotic lesions and participates in the progression of atherosclerosis. However, the role of TLR4 in vascular calcification remains unknown...
November 19, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27875258/sweat-lipid-mediator-profiling-a-non-invasive-approach-for-cutaneous-research
#13
Karan Agrawal, Lauren A Hassoun, Negar Foolad, Theresa L Pedersen, Raja K Sivamani, John William Newman
Recent advances in analytical and sweat collection techniques provide new opportunities to identify non-invasive biomarkers for the study of skin inflammation and repair. This study aims to characterize the lipid mediator profile including oxygenated lipids, endocannabinoids and ceramides/sphingoid bases in sweat and identify differences in these profiles between sweat collected from non-lesional sites on the unflared volar forearm of subjects with and without atopic dermatitis (AD). Adapting routine procedures developed for plasma analysis, over 100 lipid mediators were profiled using liquid chromatography-tandem mass spectrometry and 58 lipid mediators were detected in sweat...
November 8, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27872481/imaging-cellular-dynamics-with-spectral-relaxation-imaging-microscopy-distinct-spectral-dynamics-in-golgi-membranes-of-living-cells
#14
Alireza Lajevardipour, James W M Chon, Amitabha Chattopadhyay, Andrew H A Clayton
Spectral relaxation from fluorescent probes is a useful technique for determining the dynamics of condensed phases. To this end, we have developed a method based on wide-field spectral fluorescence lifetime imaging microscopy to extract spectral relaxation correlation times of fluorescent probes in living cells. We show that measurement of the phase and modulation of fluorescence from two wavelengths permit the identification and determination of excited state lifetimes and spectral relaxation correlation times at a single modulation frequency...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27871086/the-influence-of-two-different-foam-creams-on-skin-barrier-repair-of-foot-xerosis-a-prospective-double-blind-randomised-placebo-controlled-intra-individual-study
#15
Dorothee Daehnhardt, Stephan Daehnhardt-Pfeiffer, Judith Schulte-Walter, Thomas Neubourg, Eckhard Hanisch, Christel Schmetz, Marion Breuer, Regina Fölster-Holst
BACKGROUND/AIMS: Dry skin, or xerosis, is a common condition and a key feature of skin diseases like atopic dermatitis (AD) and ichthyosis vulgaris. Foot xerosis may exist without underlying disease and could be related to very mild forms of AD or ichthyosis vulgaris. The synthesis of important skin lipids (cholesterol, free fatty acids and ceramides) is reduced in xerosis and AD, and reduced lipid synthesis is responsible for a lack of lipids and enzymes in the skin barrier. This slows down reorganisation of the lipid lamellae in the stratum corneum (SC)...
November 22, 2016: Skin Pharmacology and Physiology
https://www.readbyqxmd.com/read/27870891/oxldl-and-eldl-induced-membrane-microdomains-in-human-macrophages
#16
Stefan Wallner, Margot Grandl, Gerhard Liebisch, Markus Peer, Evelyn Orsó, Alexander Sigrüner, Andrzej Sobota, Gerd Schmitz
BACKGROUND: Extravasation of macrophages and formation of lipid-laden foam cells are key events in the development and progression of atherosclerosis. The degradation of atherogenic lipoproteins subsequently leads to alterations in cellular lipid metabolism that influence inflammatory signaling. Especially sphingolipids and ceramides are known to be involved in these processes. We therefore analyzed monocyte derived macrophages during differentiation and after loading with enzymatically (eLDL) and oxidatively (oxLDL) modified low-density lipoproteins (LDL)...
2016: PloS One
https://www.readbyqxmd.com/read/27869314/runx1-orchestrates-sphingolipid-metabolism-and-glucocorticoid-resistance-in-lymphomagenesis
#17
A Kilbey, A Terry, S Wotton, G Borland, Q Zhang, N Mackay, A McDonald, M Bell, M J O Wakelam, E R Cameron, J C Neil
The three-membered RUNX gene family includes RUNX1, a major mutational target in human leukemias, and displays hallmarks of both tumour suppressors and oncogenes. In mouse models the Runx genes appear to act as conditional oncogenes, as ectopic expression is growth suppressive in normal cells but drives lymphoma development potently when combined with over-expressed Myc or loss of p53. Clues to underlying mechanisms emerged previously from murine fibroblasts where ectopic expression of any of the Runx genes promotes survival through direct and indirect regulation of key enzymes in sphingolipid metabolism associated with a shift in the 'sphingolipid rheostat' from ceramide to sphingosine-1-phosphate (S1P)...
November 21, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27866044/alternative-splicing-of-smpd1-coding-for-acid-sphingomyelinase-in-major-depression
#18
Cosima Rhein, Martin Reichel, Marcel Kramer, Andrea Rotter, Bernd Lenz, Christiane Mühle, Erich Gulbins, Johannes Kornhuber
BACKGROUND: Major depressive disorder (MDD) is a psychiatric disorder characterized by key symptoms that include depressed mood and a loss of interest and pleasure. A recently developed pathogenic model of MDD involves disturbed neurogenesis in the hippocampus, where the acid sphingomyelinase (ASM)/ceramide system plays an important role and is proposed as a molecular target for antidepressant action. Because alternative splicing of SMPD1 mRNA, coding for ASM, is relevant for the regulation of ASM enzymatic activity, we investigated the frequency of alternatively spliced ASM isoforms in peripheral blood cells of MDD patients versus healthy controls...
September 28, 2016: Journal of Affective Disorders
https://www.readbyqxmd.com/read/27865938/pdmp-a-ceramide-analogue-acts-as-an-inhibitor-of-mtorc1-by-inducing-its-translocation-from-lysosome-to-endoplasmic-reticulum
#19
Takashi Ode, Katarzyna A Podyma-Inoue, Kazue Terasawa, Jin-Ichi Inokuchi, Toshihide Kobayashi, Tetsuro Watabe, Yuichi Izumi, Miki Hara-Yokoyama
Mammalian or mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth, metabolism, and cell differentiation. Recent studies have revealed that the recruitment of mTORC1 to lysosomes is essential for its activation. The ceramide analogue 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), a well known glycosphingolipid synthesis inhibitor, also affects the structures and functions of various organelles, including lysosomes and endoplasmic reticulum (ER). We investigated whether PDMP regulates the mTORC1 activity through its effects on organellar behavior...
November 16, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27864687/omega-3-fatty-acid-epa-improves-regenerative-capacity-of-mouse-skeletal-muscle-cells-exposed-to-saturated-fat-and-inflammation
#20
Amarjit Saini, Adam P Sharples, Nasser Al-Shanti, Claire E Stewart
Sarcopenic obesity is characterised by high fat mass, low muscle mass and an elevated inflammatory environmental milieu. We therefore investigated the effects of elevated inflammatory cytokine TNF-α (aging/obesity) and saturated fatty acid, palmitate (obesity) on skeletal muscle cells in the presence/absence of EPA, a-3 polyunsaturated fatty acid with proposed anti-inflammatory, anti-obesity activities. In the present study we show that palmitate was lipotoxic, inducing high levels of cell death and blocking myotube formation...
November 18, 2016: Biogerontology
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