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M V Barbado, M Medrano, T Caballero-Velázquez, I Álvarez-Laderas, L I Sánchez-Abarca, E García-Guerrero, J Martín-Sánchez, I V Rosado, J I Piruat, P Gonzalez-Naranjo, N E Campillo, J A Páez, J A Pérez-Simón
Although hematopoietic and immune system show high levels of the cannabinoid receptor CB2, the potential effect of cannabinoids on hematologic malignancies has been poorly determined. Here we have investigated their anti-tumor effect in multiple myeloma (MM). We demonstrate that cannabinoids induce a selective apoptosis in MM cell lines and in primary plasma cells of MM patients, while sparing normal cells from healthy donors, including hematopoietic stem cells. This effect was mediated by caspase activation, mainly caspase-2, and was partially prevented by a pan-caspase inhibitor...
October 25, 2016: International Journal of Cancer. Journal International du Cancer
Ditte Søgaard, Torben Østergård, Agnieszka U Blachnio-Zabielska, Marcin Baranowski, Andreas Hansen Vigelsø, Jesper Løvind Andersen, Flemming Dela, Jørn Wulff Helge
Ceramide and diacylglycerol (DAG) may be involved in the early phase of insulin resistance but data are inconsistent in man. We evaluated if an increase in insulin sensitivity after endurance training was accompanied by changes in these lipids in skeletal muscle. Nineteen first-degree type 2 diabetes Offsprings (Offsprings) (age: 33.1 ± 1.4 yrs; BMI: 26.4 ± 0.4 kg/m(2)) and sixteen matched Controls (age: 31.3 ± 1.5 yrs; BMI: 25.3 ± 0.7 kg/m(2)) performed 10 weeks of endurance training three times a week at 70% of VO2max on a bicycle ergometer...
2016: Journal of Diabetes Research
Toshiyuki Yamaji, Aya Horie, Yuriko Tachida, Chisato Sakuma, Yusuke Suzuki, Yasunori Kushi, Kentaro Hanada
Ceramide is a common precursor of sphingomyelin (SM) and glycosphingolipids (GSLs) in mammalian cells. Ceramide synthase 2 (CERS2), one of the six ceramide synthase isoforms, is responsible for the synthesis of very long chain fatty acid (C20-26 fatty acids) (VLC)-containing ceramides (VLC-Cer). It is known that the proportion of VLC species in GSLs is higher than that in SM. To address the mechanism of the VLC-preference of GSLs, we used genome editing to establish three HeLa cell mutants that expressed different amounts of CERS2 and compared the acyl chain lengths of SM and GSLs by metabolic labeling experiments...
October 21, 2016: International Journal of Molecular Sciences
Yi Xing, Yi Tang, Lina Zhao, Qi Wang, Wei Qin, Xiaojuan Ji, Jinlan Zhang, Jianping Jia
BACKGROUND: The abnormal metabolism of ceramides may account for the pathogenesis of Parkinson's disease dementia (PDD). However, the effect of ceramides on cognitive domain impairments and neuropsychiatric symptoms of PDD remains unknown. METHODS: A total of 38 PDD, 40 PD with no cognitive impairment (PD-NC) and 40 normal controls were included. A series of cognitive tests and the Neuropsychiatric Inventory (NPI) were used to assess cognitive domains and neuropsychiatric symptoms...
November 15, 2016: Journal of the Neurological Sciences
Etheresia Pretorius, Jeanette N du Plooy, Janette Bester
Erythrocytes (RBCs) are extremely sensitive cells, and although they do not have nuclei and mitochondria, are important health indicators. This is particularly true because, during inflammation, whether it is systemic or chronic, the haematological system is constantly exposed to circulating inflammatory mediators. RBCs have a highly specialized and organized membrane structure, which interacts and reacts to inflammatory molecule insults, and undergo programmed cell death, similar to apoptosis, known as eryptosis...
October 24, 2016: Cellular Physiology and Biochemistry
Nicolas Coant, Wataru Sakamoto, Cungui Mao, Yusuf A Hannun
Over the past three decades, extensive research has been able to determine the biologic functions for the main bioactive sphingolipids, namely ceramide, sphingosine, and sphingosine 1-phosphate (S1P) (Hannun, 1996; Hannun et al., 1986; Okazaki et al., 1989). These studies have managed to define the metabolism, regulation, and function of these bioactive sphingolipids. This emerging body of literature has also implicated bioactive sphingolipids, particularly S1P and ceramide, as key regulators of cellular homeostasis...
October 11, 2016: Advances in Biological Regulation
Aki S Havulinna, Marko Sysi-Aho, Mika Hilvo, Dimple Kauhanen, Reini Hurme, Kim Ekroos, Veikko Salomaa, Reijo Laaksonen
OBJECTIVE: Ceramides are molecular lipids implicated in apoptosis, inflammation, obesity, and insulin resistance. An earlier study reported that ceramides were associated with fatal outcome among patients with coronary heart disease. Here, we examined whether ceramides are associated with major adverse cardiovascular events (MACEs) among apparently healthy individuals. APPROACH AND RESULTS: FINRISK 2002 is a population-based risk factor survey, which recruited men and women aged 25 to 74 years...
October 20, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Katia Roberta A Belaz, Alessandra Tata, Moana R França, Maressa I Santos da Silva, Pedro Henrique Vendramini, Anna Maria A P Fernandes, Fábio L D'Alexandri, Marcos N Eberlin, Mario Binelli
Phospholipid metabolism and signaling influences on early pregnancy events in cattle are unknown. This study aimed to characterize global phospholipid composition of oviduct and uterus during early diestrus in a model of contrasting embryo receptivity. Beef cows were treated to ovulate a larger (LF-LCL group, associated with greater receptivity) or smaller follicle (SF-SCL group) and, consequently, to present greater or smaller plasma concentrations of estradiol during proestrus-estrus as well as progesterone during early diestrus...
October 19, 2016: Biology of Reproduction
Domenico Russo, Seetharaman Parashuraman, Giovanni D'Angelo
Glycosphingolipids (GSLs) are a class of ceramide-based glycolipids essential for embryo development in mammals. The synthesis of specific GSLs depends on the expression of distinctive sets of GSL synthesizing enzymes that is tightly regulated during development. Several reports have described how cell surface receptors can be kept in a resting state or activate alternative signalling events as a consequence of their interaction with GSLs. Specific GSLs, indeed, interface with specific protein domains that are found in signalling molecules and which act as GSL sensors to modify signalling responses...
October 15, 2016: International Journal of Molecular Sciences
Tomasz Bednarski, Adam Olichwier, Agnieszka Opasinska, Aleksandra Pyrkowska, Ana-Maria Gan, James M Ntambi, Pawel Dobrzyn
Stearoyl-CoA desaturase 1 (SCD1) has recently been shown to be a critical control point in the regulation of cardiac metabolism and function. Peroxisome proliferator-activated receptor α (PPARα) is an important regulator of myocardial fatty acid uptake and utilization. The present study used SCD1 and PPARα double knockout (SCD1(-/-)/PPARα(-/-)) mice to test the hypothesis that PPARα is involved in metabolic changes in the heart that are caused by SCD1 downregulation/inhibition. SCD1 deficiency decreased the intracellular content of free fatty acids, triglycerides, and ceramide in the heart of SCD1(-/-) and SCD1(-/-)/PPARα(-/-) mice...
October 15, 2016: Biochimica et Biophysica Acta
Susanne Grond, Thomas O Eichmann, Sandrine Dubrac, Dagmar Kolb, Matthias Schmuth, Judith Fischer, Debra Crumrine, Peter M Elias, Guenter Haemmerle, Rudolf Zechner, Achim Lass, Franz P W Radner
Mutations in PNPLA1 (Patatin-like phospholipase domain-containing 1) have been identified as causative for autosomal recessive congenital ichthyosis in humans and dogs. So far, the underlying molecular mechanisms are unknown. In this study, we generated and characterized PNPLA1-deficient mice and found that PNPLA1 is crucial for epidermal sphingolipid synthesis. The absence of functional PNPLA1 in mice impaired the generation of omega-O-acylceramides and led to an accumulation of non-esterified omega-hydroxy-ceramides...
October 14, 2016: Journal of Investigative Dermatology
Lelin Hu, Hao Wang, Li Huang, Yong Zhao, Junjie Wang
Autophagy induced by radiation is critical to cell fate decision. Evidence now sheds light on the importance of autophagy induced by cancer radiotherapy. Traditional view considers radiation can directly or indirectly damage DNA which can activate DNA damage the repair signaling pathway, a large number of proteins participating in DNA damage repair signaling pathway such as p53, ATM, PARP1, FOXO3a, mTOR and SIRT1 involved in autophagy regulation. However, emerging recent evidence suggests radiation can also cause injury to extranuclear targets such as plasma membrane, mitochondria and endoplasmic reticulum (ER) and induce accumulation of ceramide, ROS, and Ca2+ concentration which activate many signaling pathways to modulate autophagy...
October 5, 2016: International Journal of Oncology
Katrin Anne Becker, Nadine Beckmann, Constantin Adams, Gabriele Hessler, Melanie Kramer, Erich Gulbins, Alexander Carpinteiro
Metastatic dissemination of cancer cells is one of the hallmarks of malignancy and accounts for approximately 90 % of human cancer deaths. Within the blood vasculature, tumor cells may aggregate with platelets to form clots, adhere to and spread onto endothelial cells, and finally extravasate to form metastatic colonies. We have previously shown that sphingolipids play a central role in the interaction of tumor cells with platelets; this interaction is a prerequisite for hematogenous tumor metastasis in at least some tumor models...
October 15, 2016: Clinical & Experimental Metastasis
Salim S Hayek, Yuri Klyachkin, Ahmed Asfour, Nima Ghasemzadeh, Mosaab Awad, Iraj Hesaroieh, Hina Ahmed, Brandon Gray, Jinhee Kim, Edmund K Waller, Arshed A Quyyumi, Ahmed K Abdel-Latif
: : Bone marrow-derived progenitor cells are mobilized into the peripheral blood after acute myocardial injury and in chronic ischemic heart disease. However, the mechanisms responsible for this mobilization are poorly understood. We examined the relationship between plasma levels of bioactive lipids and number of circulating progenitor cells (CPCs) in patients (N = 437) undergoing elective or emergent cardiac catheterization. Plasma levels of sphingosine-1 phosphate (S1P) and ceramide-1 phosphate (C1P) were quantified using mass spectrometry...
October 14, 2016: Stem Cells Translational Medicine
F G Dupuy, S P Fernández Bordín, B Maggio, R G Oliveira
Ceramides constitute a group of lipids with usually high melting temperature that also favor negative curvature in membranes when mixed with other lipids. The short chain C10:0 ceramide is an asymmetric lipid which consists of an 18 carbon sphingosine base N-acylated with decanoic acid. According to high sensitivity differential scanning calorimetry, it shows a minor exothermic peak at 61°C and a main endothermic transition at 75°C. By small angle X-ray scattering and polarized light microscopy we found that, at temperatures below the main transition, the fully hydrated lipid dispersions are arranged in a tridimensional structure corresponding to an inverted hexagonal phase...
October 5, 2016: Colloids and Surfaces. B, Biointerfaces
Alessandra Tata, Michael Woolman, Manuela Ventura, Nicholas Bernards, Milan Ganguly, Adam Gribble, Bindesh Shrestha, Emma Bluemke, Howard J Ginsberg, Alex Vitkin, Jinzi Zheng, Arash Zarrine-Afsar
Identification of necrosis in tumors is of prognostic value in treatment planning, as necrosis is associated with aggressive forms of cancer and unfavourable outcomes. To facilitate rapid detection of necrosis with Mass Spectrometry (MS), we report the lipid MS profile of necrotic breast cancer with Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) imaging validated with statistical analysis and correlating pathology. This MS profile is characterized by (1) the presence of the ion of m/z 572.48 [Cer(d34:1) + Cl](-) which is a ceramide absent from the viable cancer subregions; (2) the absence of the ion of m/z 391...
October 13, 2016: Scientific Reports
J Blaak, D Dähnhardt, S Dähnhardt-Pfeiffer, S Bielfeldt, K-P Wilhelm, R Wohlfart, P Staib
OBJECTIVE: Xerosis is a serious problem among the very old. It is a dermatological challenge caused by significant alterations in stratum corneum (SC) function and structure. Two negative changes in aged skin are: (i) the enhanced skin surface pH and (ii) the altered SC lipid content, composition and ordering. METHODS: Therefore, we investigated the way in which an acidic skin care product with different plant oils affects SC function, structure and lipid profile in older subjects with dry skin...
October 12, 2016: International Journal of Cosmetic Science
Birol Cabukusta, Jan A Köhlen, Christian P Richter, Changjiang You, Joost C M Holthuis
Single-molecule photobleaching has emerged as a powerful non-invasive approach to extract the stoichiometry of multimeric membrane proteins in their native cellular environment. However, this method has mainly been used to determine the subunit composition of ion channels and receptors at the plasma membrane. In here we applied single-molecule photobleaching to analyse the oligomeric state of an ER-resident candidate ceramide sensor protein, SMSr/SAMD8. Co-immunoprecipitation and chemical crosslinking studies previously revealed that the N-terminal sterile alpha motif or SAM domain of SMSr drives self-assembly of the protein into oligomers and that SMSr oligomerization is promoted by curcumin, a drug known to perturb ER ceramide and calcium homeostasis...
October 10, 2016: Journal of Biological Chemistry
Ismael González-García, Johan Fernø, Carlos Diéguez, Rubén Nogueiras, Miguel López
Hypothalamic lipid metabolism plays a major role in the physiological regulation of energy balance. Modulation of several enzymatic activities that control lipid biosynthesis, such as fatty acid synthase (FAS) and AMP-activated protein kinase (AMPK), impacts both feeding and energy expenditure. However, lipids can also cause pathological alterations in the hypothalamus. Lipotoxicity is promoted by excess lipids in tissues non suitable for their storage. A large amount of evidence has demonstrated that lipotoxicity is a pathophysiological mechanism leading to metabolic diseases, such as insulin resistance, cardiomyopathy, atherosclerosis and steatohepatitis...
October 11, 2016: Neuroendocrinology
Yan-Feng Zhou, Matthew C Metcalf, Scott C Garman, Tim Edmunds, Huawei Qiu, Ronnie R Wei
Acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to ceramide and phosphocholine, essential components of myelin in neurons. Genetic alterations in ASM lead to ASM deficiency (ASMD) and have been linked to Niemann-Pick disease types A and B. Olipudase alfa, a recombinant form of human ASM, is being developed as enzyme replacement therapy to treat the non-neurological manifestations of ASMD. Here we present the human ASM holoenzyme and product bound structures encompassing all of the functional domains. The catalytic domain has a metallophosphatase fold, and two zinc ions and one reaction product phosphocholine are identified in a histidine-rich active site...
October 11, 2016: Nature Communications
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