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Ceramide signaling pathway

Christiane Mühle, Christian Weinland, Erich Gulbins, Bernd Lenz, Johannes Kornhuber
By catalyzing the hydrolysis of sphingomyelin into ceramide, acid sphingomyelinase (ASM) changes the local composition of the plasma membrane with effects on receptor-mediated signaling. Altered enzyme activities have been noted in common human diseases, including alcohol dependence. However, the underlying mechanisms remain largely unresolved. Blood samples were collected from early-abstinent alcohol-dependent in-patients ( n [♂] = 113, n [♀] = 87) and matched healthy controls ( n [♂] = 133, n [♀] = 107), and analyzed for routine blood parameters and serum ASM activity...
December 13, 2018: International Journal of Molecular Sciences
Marion Orsini, Sébastien Chateauvieux, Jiyun Rhim, Anthoula Gaigneaux, David Cheillan, Christo Christov, Mario Dicato, Franck Morceau, Marc Diederich
Elevated levels of the pro-inflammatory cytokine tumor necrosis factor-α (TNFα) inhibit erythropoiesis and cause anemia in patients with cancer and chronic inflammatory diseases. TNFα is also a potent activator of the sphingomyelinase (SMase)/ceramide pathway leading to ceramide synthesis and regulating cell differentiation, proliferation, apoptosis, senescence, and autophagy. Here we evaluated the implication of the TNFα/SMase/ceramide pathway on inhibition of erythropoiesis in human CD34+ hematopoietic stem/progenitor cells (CD34/HSPCs) from healthy donors...
December 13, 2018: Cell Death and Differentiation
José Manuel Jáuregui-Wade, Jesús Valdés, Jorge Tonatiuh Ayala-Sumuano, Ricardo Ávila-García, Jorge Cerbón-Solorzano
Entamoeba invadens is a protozoan, which causes multiple damages in reptiles and is considered a prototype for the study of the Entamoeba encystment in vitro. Here we report for the first time the role of the de novo synthesis pathway of sphingolipids during the encystment of E. invadens. In silico analysis showed that this parasite has six putative genes coding for ceramide synthases (CerS), all of them coding for proteins containing the Lag1p motif, a region conserved in the ceramide synthases of multiple organisms, suggesting that they might be bona fide CerS...
December 11, 2018: Biochemical and Biophysical Research Communications
Peter Kubiniok, Brendan T Finicle, Fanny Piffaretti, Alison N McCracken, Michael Perryman, Stephen Hanessian, Aimee L Edinger, Pierre Thibault
The anti-neoplastic sphingolipid analog SH-BC-893 starves cancer cells to death by down-regulating cell surface nutrient transporters and blocking lysosomal trafficking events. These effects are mediated by the activation of protein phosphatase 2A (PP2A). To identify putative PP2A substrates, we used quantitative phosphoproteomics to profile the temporal changes in protein phosphorylation in FL5.12 cells following incubation with SH-BC-893 or the specific PP2A inhibitor LB-100. These analyses enabled the profiling of more than 15,000 phosphorylation sites, of which 958 sites on 644 proteins were dynamically regulated...
November 27, 2018: Molecular & Cellular Proteomics: MCP
Prajna Shanbhogue, Yusuf A Hannun
Sphingosine, ceramide, sphingosine-1-phosphate, and other related sphingolipids have emerged as important bioactive molecules involved in a variety of key cellular processes such as cell growth, differentiation, apoptosis, exosome release, and inter- and intracellular cell communication, making the pathways of sphingolipid metabolism a key domain in maintaining cell homeostasis (Hannun and Obeid, Trends Biochem Sci 20:73-77, 1995; Hannun and Obeid, Nat Rev Mol Cell Biol 9:139-150, 2008; Kosaka et al., J Biol Chem 288:10849-10859, 2013)...
November 27, 2018: Handbook of Experimental Pharmacology
Prashant Chauhan, Bhaskar Saha
Immunometabolic framework provides a way to understand the immune regulation via cell intrinsic metabolic fluxes and metabolites during infections, tumors, and inflammatory disorders. During these diseases, the immune cells are activated requiring more energy and moderating their metabolic functions. The two categories of metabolic alterations are therefore causally associated with energy derivation and cellular functions. Pathogens, tumors and inflammation target energy metabolism, primarily glucose uptake, glucose catabolism, gluconeogenesis for continuing lipid metabolism through mainstream pathways such as glycolysis, tricarboxylic acid cycle, mitochondrial respiration and pentose phosphate pathway...
November 21, 2018: Cytokine
Tomasz Charytoniuk, Nicoletta Iłowska, Klaudia Berk, Krzysztof Drygalski, Adrian Chabowski, Karolina Konstantynowicz-Nowicka
AIMS: Obesity and type 2 diabetes mellitus, correlate with increased tissue concentration of sphingolipids, which directly interfere with insulin signaling pathway. Phytoestrogens are a group of plant-derived compounds that have been studied in the case of metabolic disorders treatment. Therefore, the aim of this study was to ascertain whether enterolactone (ENL), a commonly known phytoestrogen, may affect sphingolipid metabolism and decrease hepatic insulin resistance development in a lipid overload state...
November 20, 2018: Life Sciences
Mariana Nikolova-Karakashian
Sphingolipids are class of metabolically distinct lipids that play structural and signaling functions in all organisms. Sphingolipid metabolism is deregulated during various diseases such as cancer, neurological and immune disorders, and metabolic syndrome. With the advancement of sphingo-lipidomics and sphingo-genomics, an understanding of the specific roles of ceramide, the quintessential bioactive sphingolipid, in fatty liver disease has taken shape. Two major pathways for ceramide generation, the de novo pathway and the sphingomyelinase pathway are activated in the course of both, the non-alcoholic and the alcoholic, forms of fatty liver disease...
December 2018: Advances in Biological Regulation
Babita Adhikari, Bhagya De Silva, Joshua A Molina, Ashton Allen, Sun H Peck, Stella Y Lee
The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative lysosomal storage disorders. CLN8 deficiency causes a subtype of NCL, referred to as CLN8 disease. CLN8 is an ER resident protein with unknown function; however, a role in ceramide metabolism has been suggested. In this report, we identified PP2A and its biological inhibitor I2PP2A as interacting proteins of CLN8. PP2A is one of the major serine/threonine phosphatases in cells and governs a wide range of signaling pathways by dephosphorylating critical signaling molecules...
November 16, 2018: Biochimica et biophysica acta. Molecular basis of disease
Panfeng Fu, Mark Shaaya, Anantha Harijith, Jeffrey R Jacobson, Andrei Karginov, Viswanathan Natarajan
Sphingolipids, first described in the brain in 1884, are important structural components of biological membranes of all eukaryotic cells. In recent years, several lines of evidence support the critical role of sphingolipids such as sphingosine, sphingosine-1-phosphate (S1P), and ceramide as anti- or pro-inflammatory bioactive lipid mediators in a variety of human pathologies including pulmonary and vascular disorders. Among the sphingolipids, S1P is a naturally occurring agonist that exhibits potent barrier enhancing property in the endothelium by signaling via G protein-coupled S1P1 receptor...
2018: Current Topics in Membranes
Guanghu Wang, Erhard Bieberich
For many decades, research on sphingolipids associated with neurodegenerative disease focused on alterations in glycosphingolipids, particularly glycosylceramides (cerebrosides), sulfatides, and gangliosides. This seemed quite natural since many of these glycolipids are constituents of myelin and accumulated in lipid storage diseases (sphingolipidoses) resulting from enzyme deficiencies in glycolipid metabolism. With the advent of recognizing ceramide and its derivative, sphingosine-1-phosphate (S1P), as key players in lipid cell signaling and regulation of cell death and survival, research focus shifted toward these two sphingolipids...
December 2018: Advances in Biological Regulation
Zhongyang Lu, Yanchun Li, Ji Hyun Ru, Maria F Lopes-Virella, Timothy J Lyons, Yan Huang
Studies have implicated saturated fatty acid (SFA) and lipopolysaccharide (LPS) in diabetic retinopathy. Since type 2 diabetes is associated with increases in both SFA and LPS in circulation, we investigated how SFA interacts with LPS to regulate proinflammatory cytokine expression and apoptosis in human retinal microvascular endothelial cells (HRMVECs) and the underlying mechanisms. HRMVECs were challenged with palmitate, a major SFA, LPS or palmitate plus LPS and the expression of proinflammatory cytokines were quantified using real-time PCR and enzyme-linked immunosorbent assay...
September 28, 2018: Experimental Eye Research
Sung Won Jang, Woo-Jae Park, Hyeonji Min, Taeg Kyu Kwon, Seong Kyu Baek, Ilseon Hwang, Shin Kim, Jong-Wook Park
Ceramide synthases (CerSs) synthesize various ceramides of different acyl chain lengths and serve important roles in the proliferation and death of cancer cells by regulating sphingolipid metabolism‑related signaling pathways. The present study investigated the mRNA expression levels of various CerS genes using mRNA expression data from six independent colorectal cancer (CRC) cohorts and a Korean CRC dataset. Expression levels of CERS2, CERS5 and CERS6 mRNA were significantly increased in the majority of the studied groups...
September 18, 2018: Oncology Reports
Liangliang Yan, Jiahui Li, Qingsong Wu, Liangwan Chen
The profile of differentially expressed microRNAs (miRNAs) in the serum of patients with cardiac myxoma (CM) (n=30) and healthy people (n=30) was studied using miRNA microarray analysis. The expression of the candidate miRNAs was validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in the serum of 30 CM patients and 30 healthy control individuals. TargetScan, PicTar and miRanda were used to predict the possible target gene of miR-320a. The Gene Ontology database and Kyoto Encyclopedia of Genes and Genomes database were used to enrich the functions and signaling pathways of the target genes, respectively...
October 2018: Oncology Letters
Emma L Sundberg, Yongqiang Deng, Christopher G Burd
Sphingolipids are structural components of organelle membranes that also participate in signal transduction pathways. Complex sphingolipids are trafficked from their site of synthesis in organelles of the early secretory pathway to the Golgi apparatus, the plasma membrane, and the endo-lysosomal system. We have developed fluorescence microscopy-based methods to monitor sphingolipid trafficking in coordination with secretory protein sorting. A sphingomyelin binding protein fused to a fluorescent protein, which we term "EQ-SM," is implemented to monitor sphingomyelin trafficking from the Golgi apparatus to the plasma membrane via secretory vesicles...
September 24, 2018: Current Protocols in Cell Biology
Min Hee Kim, Joo-Won Park, Eun-Ji Lee, Shin Kim, Sun-Hye Shin, Jung-Hyuck Ahn, Yunjae Jung, Inkeun Park, Woo-Jae Park
Recently, sphingolipid derivatives, such as ceramide and sphingosine‑1‑phosphate (S1P), have emerged as key modulators in apoptotic cell death and cell proliferation. This study aimed to clarify the underlying signaling pathways of ceramide and S1P involved in breast cancer cell proliferation. Ceramide acyl chain length is determined by six mammalian ceramide synthases (CerS). We overexpressed CerS1 to 6 in MCF‑7 cells to examine whether ceramide signaling propagation varies as a function of acyl chain length...
November 2018: Oncology Reports
Ahreum Yang, William I Suh, Nam Kyu Kang, Bongsoo Lee, Yong Keun Chang
Microalgae have great potential for the production of biofuels due to the ability of the organism to accumulate large quantities of storage lipids under stress conditions. Mitogen activated protein kinase (MAPK) signaling cascades are widely recognized for their role in stress response signal transduction in eukaryotes. To assess the correlation between MAPK activation and lipid productivity, Chlamydomonas reinhardtii was studied under various concentrations of NaCl. The results demonstrated that C. reinhardtii exhibits elevated levels of extracellular-signal regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) activities after undergoing osmotic stress, as well as an increase in cellular lipid content...
September 14, 2018: Scientific Reports
Natalia Wasilewska, Anna Bobrus-Chociej, Ewa Harasim-Symbor, Eugeniusz Tarasów, Małgorzata Wojtkowska, Adrian Chabowski, Dariusz M Lebensztejn
BACKGROUND: Hepatic lipid accumulation is closely related to the development of insulin resistance, which is regarded as one of the most significant risk factors of nonalcoholic fatty liver disease (NAFLD). Although the exact molecular pathway leading to impaired insulin signaling has not been definitively established, ceramides are suspected mediators of lipid induced hepatic insulin resistance. Therefore, the aim of the study was to evaluate the serum ceramides concentration in obese children with NAFLD...
September 12, 2018: Lipids in Health and Disease
Erhard Bieberich
About twenty years ago, the functional lipid raft model of the plasma membrane was published. It took into account decades of research showing that cellular membranes are not just homogenous mixtures of lipids and proteins. Lateral anisotropy leads to assembly of membrane domains with specific lipid and protein composition regulating vesicular traffic, cell polarity, and cell signaling pathways in a plethora of biological processes. However, what appeared to be a clearly defined entity of clustered raft lipids and proteins became increasingly fluid over the years, and many of the fundamental questions about biogenesis and structure of lipid rafts remained unanswered...
November 2018: Chemistry and Physics of Lipids
Pamela A Young, Can E Senkal, Amanda L Suchanek, Trisha J Grevengoed, Dennis D Lin, Liyang Zhao, Amanda E Crunk, Eric L Klett, Joachim Füllekrug, Lina M Obeid, Rosalind A Coleman
Fatty acid channeling into oxidation or storage modes depends on physiological conditions and hormonal signaling. However, the directionality of this channeling may also depend on the association of each of the five acyl-CoA synthetase isoforms with specific protein partners. Long-chain acyl-CoA synthetases (ACSLs) catalyze the conversion of long-chain fatty acids to fatty acyl-CoAs, which are then either oxidized or used in esterification reactions. In highly oxidative tissues, ACSL1 is located on the outer mitochondrial membrane (OMM) and directs fatty acids into mitochondria for β-oxidation...
October 26, 2018: Journal of Biological Chemistry
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