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https://www.readbyqxmd.com/read/28535537/triggering-of-suicidal-erythrocyte-death-by-exemestane
#1
Abdulla Al Mamun Bhuyan, Rosi Bissinger, Hang Cao, Florian Lang
BACKGROUND/AIMS: The steroidal aromatase inactivator exemestane blocks estrogen biosynthesis and is thus employed for the prevention and treatment of breast cancer. Exemestane is in part effective by stimulation of suicidal cell death or apoptosis. Side effects of exemestane treatment include anemia. At least in theory, exemestane induced anemia could be secondary to stimulation of suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface...
May 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28535204/colocalization-of-receptors-for-shiga-toxins-with-lipid-rafts-in-primary-human-renal-glomerular-endothelial-cells-and-influence-of-d-pdmp-on-synthesis-and-distribution-of-glycosphingolipid-receptors
#2
Nadine Legros, Gottfried Pohlentz, Jana Runde, Stefanie Dusny, Hans-Ulrich Humpf, Helge Karch, Johannes Müthing
Damage of human renal glomerular endothelial cells (HRGECs) of the kidney represents the linchpin in the pathogenesis of the hemolytic uremic syndrome (HUS) caused by Shiga toxins (Stxs) of enterohemorrhagic Escherichia coli (EHEC). We performed a comprehensive structural analysis of the Stx receptor glycosphingolipids (GSLs) globotriaosylceramide (Gb3Cer, Galα4alβ4Glcβ1Cer) and globotetraosylceramide (Gb4Cer, GalNAcβ3Galα4Galβ4Glcβ1Cer) and their distribution in lipid raft analogue detergent-resistant membranes (DRMs) and nonDRMs prepared from primary HRGECs...
May 23, 2017: Glycobiology
https://www.readbyqxmd.com/read/28531105/high-mobility-group-box-1-disrupts-metabolic-function-with-cigarette-smoke-exposure-in-a-ceramide-dependent-manner
#3
Oliver J Taylor, Mikayla O Thatcher, Sheryl T Carr, Jonathan L Gibbs, Annie M Trumbull, Mitchell E Harrison, Duane R Winden, Mackenzie J Pearson, Trevor S Tippetts, William L Holland, Paul R Reynolds, Benjamin T Bikman
We have previously found that cigarette smoke disrupts metabolic function, in part, by increasing muscle ceramide accrual. To further our understanding of this, we sought to determine the role of the cytokine high-mobility group box 1 (HMGB1), which is increased with smoke exposure, in smoke-induced muscle metabolic perturbations. To test this theory, we determined HMGB1 from lungs of human smokers, as well as from lung cells from mice exposed to cigarette smoke. We also treated cells and mice directly with HMGB1, in the presence or absence of myriocin, an inhibitor of serine palmitoyltransferase, the rate-limiting enzyme in ceramide biosynthesis...
May 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28528321/omega-3-fatty-acids-lipids-and-apoe-lipidation-in-alzheimer-s-disease-a-rationale-for-multi-nutrient-dementia-prevention
#4
Marcus O Grimm, Daniel Michaelson, Tobias Hartmann
In the last decade it has become obvious that Alzheimer's disease (AD) is closely linked to changes in lipids or lipid metabolism. One of the main pathological hallmarks of AD is amyloid-β (Aβ) deposition. Aβ is derived from sequential proteolytic processing of the amyloid precursor protein (APP). Interestingly, both, the APP and all APP secretases are transmembrane proteins which cleave APP close to and in the lipid bilayer. Moreover, apolipoprotein E4 (apoE4) has been identified as the most prevalent genetic risk factor for AD...
May 20, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28525763/principles-of-chemical-biology-from-antibiotic-resistance-to-rna-targeted-therapy-via-autoxidation-and-lipid-droplets
#5
(no author information available yet)
This month: Ribosome mutations and multi-antibiotic resistance, role of autoxidation in ferroptosis, ceramide metabolism, and finding RNA drug targets.
May 18, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28522731/effect-of-metformin-on-bioactive-lipid-metabolism-in-insulin-resistant-muscle
#6
Piotr Zabielski, Marta Chacinska, Karol Charkiewicz, Marcin Baranowski, Jan Gorski, Agnieszka U Blachnio-Zabielska
Intramuscular accumulation of bioactive lipids leads to insulin resistance and type 2 diabetes (T2D). There is lack of consensus concerning which of the lipid mediators has the greatest impact on muscle insulin action in vivo Our aim was to elucidate the effects of high-fat diet (HFD) and metformin (Met) on skeletal muscle bioactive lipid accumulation and insulin resistance (IR) in rats. We employed a [U-(13)C]palmitate isotope tracer and mass spectrometry to measure the content and fractional synthesis rate (FSR) of intramuscular long-chain acyl-CoA (LCACoA), diacylglycerols (DAG) and ceramide (Cer)...
June 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28522594/sphingomyelin-synthase-2-deficiency-inhibits-the-induction-of-murine-colitis-associated-colon-cancer
#7
Toshio Ohnishi, Chieko Hashizume, Makoto Taniguchi, Hidehiro Furumoto, Jia Han, Rongfen Gao, Shinichi Kinami, Takeo Kosaka, Toshiro Okazaki
Sphingomyelin synthase 2 (SMS2) is the synthetic enzyme of sphingomyelin (SM), which regulates membrane fluidity and microdomain structure. SMS2 plays a role in LPS-induced lung injury and inflammation; however, its role in inflammation-mediated tumorigenesis is unclear. We investigated the effect of SMS2 deficiency on dextran sodium sulfate (DSS)-induced murine colitis and found inhibition of DSS-induced inflammation in SMS2-deficient (SMS2(-/-)) mice. DSS treatment induced a significant increase in ceramide levels, with a decrease of SM levels in SMS2(-/-) colon tissue, and demonstrated attenuation of the elevation of both inflammation-related gene expression and proinflammatory cytokines and chemokines, leukocyte infiltration, and MAPK and signal transducer and activator of transcription 3 activation...
May 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28520810/long-chain-saturated-and-unsaturated-fatty-acids-exert-opposing-effects-on-viability-and-function-of-glp-1-producing-cells-mechanisms-of-lipotoxicity
#8
Ketan Thombare, Stelia Ntika, Xuan Wang, Camilla Krizhanovskii
BACKGROUND AND AIM: Fatty acids acutely stimulate GLP-1 secretion from L-cells in vivo. However, a high fat diet has been shown to reduce the density of L-cells in the mouse intestine and a positive correlation has been indicated between L-cell number and GLP-1 secretion. Thus, the mechanism of fatty acid-stimulated GLP-1 secretion, potential effects of long-term exposure to elevated levels of different fatty acid species, and underlying mechanisms are not fully understood. In the present study, we sought to determine how long-term exposure to saturated (16:0) and unsaturated (18:1) fatty acids, by direct effects on GLP-1-producing cells, alter function and viability, and the underlying mechanisms...
2017: PloS One
https://www.readbyqxmd.com/read/28515456/metabolomic-analysis-shows-differential-hepatic-effects-of-t2-and-t3-in-rats-after-short-term-feeding-with-high-fat-diet
#9
Liliana F Iannucci, Federica Cioffi, Rosalba Senese, Fernando Goglia, Antonia Lanni, Paul M Yen, Rohit A Sinha
Nonalcoholic fatty liver disease (NAFLD) is a major health problem worldwide, and is often associated with lipotoxic injury, defective mitochondrial function, and insulin resistance. Thyroid hormones (THs) are important regulators of hepatic lipid metabolism. Among the THs, diiodothyronine (T2) and triiodothyronine (T3) have shown promising results in lowering hepatic fat content in various models of NAFLD. In this study, we used a targeted metabolomics approach to investigate the differential effects of T2 and T3 on the early metabolic adaptation in the livers of rats fed high fat diet (HFD), a period when hepatosteatosis is reversible...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28515365/ceramide-synthesis-regulates-t-cell-activity-and-gvhd-development
#10
M Hanief Sofi, Jessica Heinrichs, Mohammed Dany, Hung Nguyen, Min Dai, David Bastian, Steven Schutt, Yongxia Wu, Anusara Daenthanasanmak, Salih Gencer, Aleksandra Zivkovic, Zdzislaw Szulc, Holger Stark, Chen Liu, Ying-Jun Chang, Besim Ogretmen, Xue-Zhong Yu
Allogeneic hematopoietic cell transplantation (allo-HCT) is an effective immunotherapy for a variety of hematologic malignances, yet its efficacy is impeded by the development of graft-versus-host disease (GVHD). GVHD is characterized by activation, expansion, cytokine production, and migration of alloreactive donor T cells. Hence, strategies to limit GVHD are highly desirable. Ceramides are known to contribute to inflammation and autoimmunity. However, their involvement in T-cell responses to alloantigens is undefined...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28515139/changes-in-ceramide-metabolism-are-essential-in-madin-darby-canine-kidney-cell-differentiation
#11
Lucila Gisele Pescio, Bruno Jaime Santacreu, Vanina Gisela Lopez, Carlos Humberto Paván, Daniela Judith Romero, Nicolás Octavio Favale, Norma Beatriz Sterin-Speziale
Ceramides and complex sphingolipids with defined acyl-chain lengths play important roles in numerous cell processes. Six ceramide synthase isoenzymes (CerS1-6) are the key enzymes responsible for the production of the diversity of molecular species. In this study, we investigated the changes in sphingolipid metabolism during the differentiation of Madin-Darby Canine Kidney (MDCK) cells. By MALDI TOF TOF MS, we analyzed the molecular species of ceramide (Cer), glucosylceramide (GlcCer), lactosylceramide (LacCer) and sphingomyelin (SM) in non-differentiated and differentiated cells (cultured under hypertonicity)...
May 17, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28510438/complex-effects-of-24-1-sphingolipids-in-membranes-containing-dioleoyl-phosphatidylcholine-and-cholesterol
#12
Aritz B Garcia-Arribas, Emilio J Gonzalez-Ramirez, Jesús Sot, Itziar Areso, Alicia Alonso, Felix M Goni
The effects of C24:1 sphingolipids have been tested in phospholipid bilayers containing cholesterol. Confocal microscopy, differential scanning calorimetry, and atomic force microscopy imaging and force curves have been used. More precisely, the effects of C24:1 ceramide (nervonoyl ceramide, nCer) were evaluated and compared to those of C16:0 ceramide (palmitoyl ceramide, pCer) in bilayers composed basically of dioleoyl phosphatidylcholine, sphingomyelin (either C24:1, nSM or C16:0, pSM) and cholesterol. Combination of equimolecular amounts of C24:1 and C16:0 sphingolipids were also studied under the same conditions...
May 16, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28509929/borinic-acid-catalyzed-stereo-and-site-selective-synthesis-of-%C3%AE-glycosylceramides
#13
Kyan A D'Angelo, Mark S Taylor
A method for activation of unprotected ceramides towards stereo- and site-selective glycosylation is described. Two-point binding of a diarylborinic acid catalyst to the ceramide accelerates its reactions with 'armed' glycosyl methanesulfonate donors, resulting in the formation of a β-glycosidic linkage at the primary OH group.
May 16, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28507162/lipophagy-prevents-activity-dependent-neurodegeneration-due-to-dihydroceramide-accumulation-in-vivo
#14
Wei-Hung Jung, Chung-Chih Liu, Yu-Lian Yu, Yu-Chin Chang, Wen-Yu Lien, Hsi-Chun Chao, Shu-Yi Huang, Ching-Hua Kuo, Han-Chen Ho, Chih-Chiang Chan
Dihydroceramide desaturases are evolutionarily conserved enzymes that convert dihydroceramide (dhCer) to ceramide (Cer). While elevated Cer levels cause neurodegenerative diseases, the neuronal activity of its direct precursor, dhCer, remains unclear. We show that knockout of the fly dhCer desaturase gene, infertile crescent (ifc), results in larval lethality with increased dhCer and decreased Cer levels. Light stimulation leads to ROS increase and apoptotic cell death in ifc-KO photoreceptors, resulting in activity-dependent neurodegeneration...
May 15, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28504963/novel-pleiotropic-effects-of-bioactive-phospholipids-in-human-lung-cancer-metastasis
#15
Gabriela Schneider, Zachariah Payne Sellers, Kamila Bujko, Sham S Kakar, Magda Kucia, Mariusz Z Ratajczak
We previously proposed that one of the unwanted side effects of chemotherapy and radiotherapy is the increase in several peptide- and non-peptide based chemoattractants in damaged tissues, leading to induction of a prometastatic microenvironment for remaining cancer cells. Herein, we turned out our attention to a potential role of bioactive phospholipids (BphsLs), such as sphingosine-1-phosphate (S1P), ceramide-1-phosphate (C1P), lysophosphatidylcholine (LPC), and lysophosphatidic acid (LPA) in lung cancer (LC) metastasis...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28502199/ceramide-lipid-based-nanosuspension-for-enhanced-delivery-of-docetaxel-with-synergistic-antitumor-efficiency
#16
Tianqi Wang, Lixia Feng, Shaomei Yang, Yongjun Liu, Na Zhang
Ceramide (CE), a bioactive lipid with tumor suppression, has been widely used as a drug carrier and enhancer for cancer therapy. CE-based combination therapy was prone to be attractive in cancer therapy. In our previous study, the combination of CE and docetaxel (DTX) was proved to be an effective strategy for cancer therapy. To further improve the antitumor efficiency of DTX, the CE lipid-based nanosuspensions (LNS) was prepared for the delivery of DTX to exhibit synergistic therapeutic effect. The enhanced delivery and synergistic therapeutic effect of DTX-loaded CE-LNS (CE + DTX-LNS) were evaluated...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28500248/the-association-of-the-lipidomic-profile-with-features-of-polycystic-ovary-syndrome
#17
Lisa Moran, Piyushkumar Mundra, Helena Teede, Peter J Miekle
Polycystic ovary syndrome (PCOS) affects up to 18% of reproductive-aged women with reproductive and metabolic complications. While lipidomics can identify associations between lipid species and metabolic diseases, no research has examined the association of lipid species with the pathophysiological features of PCOS. The aim of this study was to examine the lipidomic profile in women with and without PCOS. This study was a cross-sectional study in 156 age-matched pre-menopausal women (18-45 years, BMI>25 kg/m2; n=92 with PCOS, n=64 without PCOS)...
May 12, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28499696/fenofibrate-decreases-plasma-ceramide-in-type-2-diabetes-patients-a-novel-marker-of-cvd
#18
M Croyal, Z Kaabia, L León, S Ramin-Mangata, T Baty, F Fall, S Billon-Crossouard, A Aguesse, T Hollstein, D R Sullivan, E Nobecourt, G Lambert, M Krempf
AIM: The benefit of the lipid-lowering drug fenofibrate on cardiovascular outcomes is controversial. Our aim was to find new circulating markers to identify those patients most likely to benefit from fenofibrate prescription. METHODS: Analyses were conducted of plasma samples collected from 102 patients with type 2 diabetes, enrolled in the FIELD trial, before and after fenofibrate treatment (200mg/day). Non-targeted and targeted lipid analyses and apolipoprotein measurements were made using mass spectrometry methods...
May 9, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28495865/ceramide-counteracts-the-effects-of-ghrelin-on-the-metabolic-control-of-food-intake-in-rainbow-trout
#19
Cristina Velasco, Guillermo Moreiras, Marta Conde-Sieira, José M Leao, Jesús M Míguez, José L Soengas
In mammals ceramides are involved in the modulation of the orexigenic effects of ghrelin (GHRL). We previously demonstrated in rainbow trout that intracerebroventricular (ICV) treatment with ceramide (2.5 µg/100g fish) resulted in an anorexigenic response, i.e. a response opposed to that described in mammals where ceramide treatment is orexigenic. Therefore, we hypothesize that the putative interaction between GHRL and ceramide must be different in fish. Accordingly, in a first experiment we observed that ceramide levels in hypothalamus of rainbow trout did not change after ICV treatment with GHRL...
May 11, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28490444/inhibiting-glucosylceramide-synthase-exacerbates-cisplatin-induced-acute-kidney-injury
#20
Tess V Dupre, Mark A Doll, Parag P Shah, Cierra N Sharp, Deanna Siow, Judit Megyesi, James Shayman, Alicja Bielwska, Jacek Bielawski, Levi J Beverly, Maria Hernandez-Corbacho, Christopher J Clarke, Ashley J Snider, Rick G Schnellmann, Lina M Obeid, Yusuf A Hannun, Leah J Siskind
Acute kidney injury (AKI), resulting from chemotherapeutic agents such as cisplatin, remains an obstacle in the treatment of cancer. Cisplatin-induced AKI involves apoptotic and necrotic cell death, pathways regulated by sphingolipids such as ceramide and glucosylceramide. Results from this study indicate that C57BL/6J mice treated with cisplatin had increased ceramide and hexosylceramide levels in the renal cortex 72 h following cisplatin treatment. Pre-treatment of mice with inhibitors of acid sphingomyelinase and de novo ceramide synthesis (amitriptyline and myriocin, respectively) prevented accumulation of ceramides and hexosylceramide in the renal cortex and protected from cisplatin-induced AKI...
May 10, 2017: Journal of Lipid Research
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