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Ceramide signaling pathway

Mélanie Ormancey, Patrice Thuleau, Renier A L van der Hoorn, Sabine Grat, Ambroise Testard, Khaled Y Kamal, Marie Boudsocq, Valérie Cotelle, Christian Mazars
It is now well established that sphingoid Long Chain Bases (LCBs) are crucial mediators of programmed cell death. In plants, the mycotoxin fumonisin B1 (FB1) produced by the necrotrophic fungus Fusarium moniliforme disrupts the sphingolipid biosynthesis pathway by inhibiting the ceramide synthase leading to an increase in the amount of phytosphingosine (PHS) and dihydrosphingosine (DHS), the two major LCBs in Arabidopsis thaliana. To date, the signaling pathway involved in FB1-induced cell death remains largely uncharacterized...
March 2019: Plant Science: An International Journal of Experimental Plant Biology
H Yaribeygi, S Bo, M Ruscica, A Sahebkar
Recent evidence suggests that ceramides can play an important pathophysiological role in the development of diabetes. Ceramides are primarily recognized as lipid bilayer building blocks, but recent work has shown that these endogenous molecules are important intracellular signalling mediators and may exert some diabetogenic effects via molecular pathways involved in insulin resistance, β-cell apoptosis and inflammation. In the present review, we consider the available evidence on the possible roles of ceramides in diabetes mellitus and introduce eight different molecular mechanisms mediating the diabetogenic action of ceramides, categorized into those predominantly related to insulin resistance vs those mainly implicated in β-cell dysfunction...
February 25, 2019: Diabetic Medicine: a Journal of the British Diabetic Association
Stephanie Sarai Loza-Medrano, Luis Arturo Baiza-Gutman, Miguel Ángel Ibáñez-Hernández, Miguel Cruz-López, Margarita Díaz-Flores
Scientific evidence has identified that the excessive consumption of products made from high-fructose corn syrup is a trigger for obesity, whose prevalence increased in recent years. Due to the metabolic characteristics of fructose, a rapid gastric emptying is produced, altering signals of hunger-satiety and decreasing the appetite. In addition to the hepatic level during catabolism, triose phosphate is generated and adenosine triphosphate (ATP) is reduced, producing uric acid. Triose phosphate triggers the synthesis of fatty acids that increase the production and accumulation of triglycerides, diacylglycerols and ceramides that induce insulin resistance...
January 28, 2019: Revista Médica del Instituto Mexicano del Seguro Social
Kehong Zheng, Zetao Chen, Haizhan Feng, Ying Chen, Cheng Zhang, Jinlong Yu, Yunfeng Luo, Liang Zhao, Xiancheng Jiang, Fujun Shi
Breast cancer is the most common type of carcinoma in women worldwide, but the mechanisms underlying tumour development and progression remain unclear. Sphingomyelin synthase 2 (SGMS2) is a crucial regulator involved in ceramide (Cer) and sphingomyelin (SM) homoeostasis that is mostly studied for its role in lipid metabolism. Our primary study indicated that high SGMS2 expression is associated with breast cancer metastasis. Gain- and loss-of-function assays in vitro and in vivo revealed that SGMS2 promotes cancer cell proliferation by suppressing apoptosis through a Cer-associated pathway and promotes cancer cell invasiveness by enhancing epithelial-to-mesenchymal transition (EMT) initiation through the TGF-β/Smad signalling pathway...
February 15, 2019: Cell Death & Disease
Arnout Mieremet, Rianne van Dijk, Gert Gooris, Joke A Bouwstra, Abdoelwaheb El Ghalbzouri
Human skin equivalents (HSEs) are three dimensional models resembling native human skin (NHS) in many aspects. Despite the manifold similarities to NHS, a restriction in its applications is the altered in vitro lipid barrier formation, which compromises the barrier functionality. This could be induced by suboptimal cell culturing conditions, which amongst others is the diminished activation of the vitamin D receptor (VDR) signalling pathway. The active metabolite of this signalling pathway is 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 )...
January 31, 2019: Journal of Steroid Biochemistry and Molecular Biology
Sweta Ghosh, Junaid Jibran Jawed, Kuntal Halder, Sayantan Banerjee, Bidisha Paul Chowdhury, Akata Saha, Subir Kumar Juin, Suchandra Bhattacharyya Majumdar, Anamika Bose, Rathindranath Baral, Subrata Majumdar
Ceramide is one of the important cellular components involved in cancer regulation and exerts its pleiotropic role in the protective immune response without exhibiting any adverse effects during malignant neoplasm. Although, the PKCδ-ceramide axis in cancer cells has been an effective target in reduction of cancer, involvement of PKCδ in inducing nephrotoxicity have become a major questionnaire. In the present study, we have elucidated the mechanism by which cisplatin exploits the ceramide to render cancer cell apoptosis leading to the abrogation of malignancy in a PKCδ independent pathway with lesser toxicity...
December 28, 2018: Oncotarget
Nadia Soudani, Rouba Hage-Sleiman, Walid Karam, Ghassan Dbaibo, Hassan Zaraket
Annual influenza outbreaks are associated with significant morbidity and mortality worldwide despite the availability of seasonal vaccines. Influenza pathogenesis depends on the manipulation of host cell signaling to promote virus replication. Ceramide is a sphingosine-derived lipid that regulates diverse cellular processes. Studies highlighted the differential role of ceramide de novo biosynthesis on the propagation of various viruses. Whether ceramide plays, a role in influenza virus replication is not known...
January 30, 2019: Journal of Virology
Teresa M Dunn, Cynthia J Tifft, Richard L Proia
The sphingolipid (SL) metabolic pathway generates structurally diverse lipids that have roles as membrane constituents and as bioactive signaling molecules. The influence of the SL metabolic pathway in biology is pervasive; it exists in all mammalian cells and has roles in many cellular and physiological pathways. Human genetic diseases have long been recognized to be caused by mutations in the pathway, but until recently these mutational defects were only known to affect lysosomal SL degradation. Now, with a nearly complete delineation of the genes constituting the SL metabolic pathway, a growing number of additional genetic disorders caused by mutations in genes within other sectors of the pathway - de novo ceramide synthesis, glycosphingolipid synthesis, and non-lysosomal SL degradation - have been recognized...
January 25, 2019: Journal of Lipid Research
Cécile L Bandet, Sophie Tan-Chen, Olivier Bourron, Hervé Le Stunff, Eric Hajduch
Insulin-resistance is a characteristic feature of type 2 diabetes (T2D) and plays a major role in the pathogenesis of this disease. Skeletal muscles are quantitatively the biggest glucose users in response to insulin and are considered as main targets in development of insulin-resistance. It is now clear that circulating fatty acids (FA), which are highly increased in T2D, play a major role in the development of muscle insulin-resistance. In healthy individuals, excess FA are stored as lipid droplets in adipocytes...
January 23, 2019: International Journal of Molecular Sciences
Peisi Xie, Chao Zhao, Wei Huang, Ting Yong, Arthur C K Chung, Kaiwu He, Xiangfeng Chen, Zongwei Cai
Prenatal exposure to ambient fine particles (diameter < 0.25 μm, PM2.5 ) has been found to be associated with abnormal growth and development in offspring. However, the effects of PM2.5 on the lipid metabolism of adipose tissue in offspring are unclear. In the present study, we established a mouse model of prenatal exposure to PM2.5 by intratracheal instillation to pregnant C57BL/6 female mice with PM2.5 suspension or normal saline. We found that prenatal exposure to PM2.5 of a mouse model reduced body weight in adult male offspring after 6 weeks old...
March 20, 2019: Science of the Total Environment
Xin Li, Hui-Fang Wang, Xiao-Xue Li, Ming Xu
AIMS: Vascular adventitial fibroblasts (AFs) in the vascular remodeling during atherosclerosis are increasing arousing attention. Acid sphingomyelinase (ASM) is a soluble glycoprotein which is involved in the development and progression of atherosclerosis. However, it remains unknown if ASM is expressed in vascular AFs and regulates vascular adventitial remodeling and underlying mechanisms. MAIN METHODS AND KEY FINDINGS: ASM downregulation with gene silencing was used in the rat AFs treated with angiotensin (Ang) II, which is universally demonstrated to induce vascular adventitia remodeling...
January 21, 2019: Life Sciences
Angel Cogolludo, Eduardo Villamor, Francisco Perez-Vizcaino, Laura Moreno
In addition to playing a role as a structural component of cellular membranes, ceramide is now clearly recognized as a bioactive lipid implicated in a variety of physiological functions. This review aims to provide updated information on the role of ceramide in the regulation of vascular tone. Ceramide may induce vasodilator or vasoconstrictor effects by interacting with several signaling pathways in endothelial and smooth muscle cells. There is a clear, albeit complex, interaction between ceramide and redox signaling...
January 18, 2019: International Journal of Molecular Sciences
Sung Min Cho, Ho Jeong Kwon
Sphingolipid metabolism plays an important role in determining the fate of a cell. Among several sphingolipid metabolites, ceramide is a key player in intracellular signal transduction. Ceramide is usually converted to various metabolites such as sphingomyelin, sphingosine, ceramide-1-phosphate, and glucosylceramide. If ceramide is accumulated in the cell, it induces apoptosis. On the other hand, its metabolite sphingosine is converted to sphingosine-1-phosphate (S1P), which promotes angiogenesis via G protein coupled receptor signaling...
January 19, 2019: Archives of Pharmacal Research
Jaganmay Sarkar, Tapati Chakraborti, Animesh Chowdhury, Rajabrata Bhuyan, Sajal Chakraborti
The signalling pathway involving MMP-2 and sphingosine-1-phosphate (S1P) in endothelin-1 (ET-1) induced pulmonary artery smooth muscle cell (PASMC) proliferation is not clearly known. We, therefore, investigated the role of NADPH oxidase derived O2 .- -mediated modulation of MMP2-sphingomyeline-ceramide-S1P signalling axis in ET-1 induced increase in proliferation of PASMCs. Additionally, protective role of the tea cathechin, epigallocatechin-3-gallate (EGCG), if any, in this scenario has also been explored...
January 19, 2019: Journal of Cell Communication and Signaling
Liping Qiu, Liangjing Chen, Xiaobo Yang, Anfang Ye, Wei Jiang, Wenjun Sun
Extremely low frequency electromagnetic field (ELF-EMF) is a kind of physical stimulus in public and occupational environment. Numerous studies have indicated that exposure of cells to ELF-EMF could promote cell proliferation. But the detailed mechanisms implicated in these proliferative processes remain unclear. In the present experiment, the possible roles of sphingosine-1-phosphate (S1P) in 50-Hz magnetic field (MF)-induced cell proliferation were investigated. Results showed that exposure of human amniotic (FL) cells to a 50-Hz MF with an intensity of 0...
January 9, 2019: Journal of Cellular Physiology
Seigo Usuki, Noriko Tamura, Tomohiro Tamura, Shigeki Higashiyama, Kunikazu Tanji, Susumu Mitsutake, Asuka Inoue, Junken Aoki, Katsuyuki Mukai, Yasuyuki Igarashi
Previously, we proposed the following mechanism for konjac ceramide (kCer)-mediated neurite outgrowth inhibition: kCer binds to Nrp as a Sema3A agonist, resulting in Nrp1/PlexA complex formation and activation of the Sema3A signaling pathway to induce phosphorylation of CRMP2 and microtubule depolymerization. The Sema3A/Nrp1 signaling pathway is known to be also expressed in normal human keratinocytes. To determine whether kCer can function in human keratinocytes as it does in neurites, that is, if it can bind to Nrp1 in place of Sema3A, we studied the effect of kCer on HaCaT cell migration activity...
March 2019: Biochemistry and Biophysics Reports
Vahid Reza Askari, Reza Shafiee-Nick
AIMS: Neuroinflammation is observed as a routine characterization of neurodegenerative disorders such as dementia, multiple sclerosis (MS) and Alzheimer's diseases (AD). Scientific evidence propounds both of the neuromodulatory and immunomodulatory effects of CB2 in the immune system. β-Caryophyllene (BCP) is a dietary selective CB2 agonist, which deserves the anti-inflammatory and antioxidant effects at both low and high doses through activation of the CB2 receptor. METHODS: In this study, we investigated the protective effects of a broad range concentration of BCP against LPS-induced primary microglia cells inflammation and M1 /M2 imbalance and identifying the portion of the involvement of related signaling pathways on BCP effects using pharmacological antagonists of CB2 , PPAR-γ, and sphingomyelinase (SMase)...
January 5, 2019: Life Sciences
Gergely Karsai, Florian Kraft, Natja Haag, G Christoph Korenke, Benjamin Hänisch, Alaa Othman, Saranya Suriyanarayanan, Regula Steiner, Cordula Knopp, Michael Mull, Markus Bergmann, J Michael Schröder, Joachim Weis, Miriam Elbracht, Matthias Begemann, Thorsten Hornemann, Ingo Kurth
BACKGROUND: Sphingolipids are important components of cellular membranes and functionally associated with fundamental processes such as cell differentiation, neuronal signaling and myelin sheath formation. Defects in the synthesis or degradation of sphingolipids leads to various neurological pathologies, however, the entire spectrum of sphingolipid metabolism disorders remained elusive. METHODS: A combined approach of genomics and lipidomics was applied to identify and characterize a human sphingolipid metabolism disorder...
January 8, 2019: Journal of Clinical Investigation
Kinga Czubowicz, Henryk Jęśko, Przemysław Wencel, Walter J Lukiw, Robert P Strosznajder
Bioactive sphingolipids-ceramide, sphingosine, and their respective 1-phosphates (C1P and S1P)-are signaling molecules serving as intracellular second messengers. Moreover, S1P acts through G protein-coupled receptors in the plasma membrane. Accumulating evidence points to sphingolipids' engagement in brain aging and in neurodegenerative disorders such as Alzheimer's, Parkinson's, and Huntington's diseases and amyotrophic lateral sclerosis. Metabolic alterations observed in the course of neurodegeneration favor ceramide-dependent pro-apoptotic signaling, while the levels of the neuroprotective S1P are reduced...
January 5, 2019: Molecular Neurobiology
Adam J Black, Rudolf J Schilder, Scot R Kimball
Background: In a previous study, we showed that consumption of diets enriched in saturated fatty acids causes changes in alternative splicing of pre-mRNAs encoding a number of proteins in rat skeletal muscle, including the one encoding skeletal muscle Troponin T ( Tnnt3 ). However, whether saturated fatty acids act directly on muscle cells to modulate alternative pre-mRNA splicing was not assessed. Moreover, the signaling pathway through which saturated fatty acids act to promote changes in alternative splicing is unknown...
2018: Nutrition & Metabolism
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