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Ceramide signaling pathway

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...
September 22, 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...
September 5, 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...
September 6, 2018: Journal of Biological Chemistry
Tetsuro Ishii, Eiji Warabi, Giovanni E Mann
Astrocyte-neuron interactions protect neurons from iron-mediated toxicity. As dopamine can be metabolized to reactive quinones, dopaminergic neurons are susceptible to oxidative damage and ferroptosis-like induced cell death. Detoxification enzymes are required to protect neurons. Brain-derived neurotrophic factor (BDNF) plays a key role in the regulation of redox sensitive transcription factor Nrf2 in astrocytes and metabolic cooperation between astrocytes and neurons. This article reviews the importance of BDNF and astrocyte-neuron interactions in the protection of neurons against oxidative damages in rodent brains...
September 4, 2018: Free Radical Biology & Medicine
Victor García-González, José Fernando Díaz-Villanueva, Octavio Galindo-Hernández, Israel Martínez-Navarro, Gustavo Hurtado-Ureta, Abril Alicia Pérez-Arias
Ceramides are key lipids in energetic-metabolic pathways and signaling cascades, modulating critical physiological functions in cells. While synthesis of ceramides is performed in endoplasmic reticulum (ER), which is altered under overnutrition conditions, proteins associated with ceramide metabolism are located on membrane arrangement of mitochondria and ER (MAMs). However, ceramide accumulation in meta-inflammation, condition that associates obesity with a chronic low-grade inflammatory state, favors the deregulation of pathways such as insulin signaling, and induces structural rearrangements on mitochondrial membrane, modifying its permeability and altering the flux of ions and other molecules...
August 26, 2018: International Journal of Molecular Sciences
Kyong-Oh Shin, Sung Jay Choe, Yoshikazu Uchida, Inyong Kim, Yoonhwa Jeong, Kyungho Park
The cutaneous wound healing process is tightly regulated by a range of cellular responses, including migration. Sphingosine-1-phosphate (S1P) is a signaling lipid produced in keratinocytes (KC) and it is known to stimulate skin wound repair through increased KC migration. Of the multifunctional triterpene ginsenosides, Rb1 enhances cutaneous wound healing process by increasing KC migration, but cellular mechanisms responsible for the Rb1-mediated increase in KC migration are largely unknown. Therefore, we hypothesized that, and assessed whether, Rb1 could stimulate KC migration through S1P-dependent mechanisms...
August 27, 2018: Journal of Medicinal Food
Henryk Jęśko, Adam Stępień, Walter J Lukiw, Robert P Strosznajder
Bioactive sphingolipids: sphingosine, sphingosine-1-phosphate (S1P), ceramide, and ceramide-1-phosphate (C1P) are increasingly implicated in cell survival, proliferation, differentiation, and in multiple aspects of stress response in the nervous system. The opposite roles of closely related sphingolipid species in cell survival/death signaling is reflected in the concept of tightly controlled sphingolipid rheostat. Aging has a complex influence on sphingolipid metabolism, disturbing signaling pathways and the properties of lipid membranes...
August 23, 2018: Molecular Neurobiology
Yih-Huei Uen, Chia-Lang Fang, Chih-Chan Lin, You-Cheng Hseu, Shih-Ting Hung, Ding-Ping Sun, Kai-Yuan Lin
Although gastric cancer (GC) is one of the most common cancers, knowledge of its development, and carcinogenesis is limited. The present study explored the involvement of ceramide synthase 6 (CERS6) in GC carcinogenesis and prognosis. RT-PCR, immunoblotting, and immunohistochemistry were used to examine the expression of CERS6. Transfection and small hairpin RNA technology were used to investigate the effect of CERS6 manipulation on cell proliferation and spread as well as the underlying mechanism. Moreover, xenograft proliferation was employed to explore the influence of CERS6 on tumor growth in animals...
August 21, 2018: Molecular Carcinogenesis
Mario A Rodríguez, Aarón Martínez-Higuera, Martha I Valle-Solis, Mario Hernandes-Alejandro, Bibiana Chávez-Munguía, Ana H Figueroa-Gutiérrez, Andrés Salas-Casas
Calcium regulates many cellular processes in protozoa, including growth, differentiation, programmed cell death, exocytosis, endocytosis, phagocytosis, fusion of the endosomes of distinct stages with phagosomes, fusion of phagosomes with lysosomes, and recycling the membrane. In Entamoeba histolytica, the protozoa responsible for human amoebiasis, calcium ions are essential for signaling pathways that lead to growth and development. In addition, calcium is crucial in the modulation of gene expression in this microorganism...
November 2018: Parasitology Research
Max C Petersen, Gerald I Shulman
The 1921 discovery of insulin was a Big Bang from which a vast and expanding universe of research into insulin action and resistance has issued. In the intervening century, some discoveries have matured, coalescing into solid and fertile ground for clinical application; others remain incompletely investigated and scientifically controversial. Here, we attempt to synthesize this work to guide further mechanistic investigation and to inform the development of novel therapies for type 2 diabetes (T2D). The rational development of such therapies necessitates detailed knowledge of one of the key pathophysiological processes involved in T2D: insulin resistance...
October 1, 2018: Physiological Reviews
Megan M Young, Hong-Gang Wang
Macroautophagy (herein referred to as autophagy) is a highly conserved stress response that engulfs damaged proteins, lipids, and/or organelles within double-membrane vesicles called autophagosomes for lysosomal degradation. Dysregulated autophagy is a hallmark of cancer; and thus, there is great interest in modulating autophagy for cancer therapy. Sphingolipids regulate each step of autophagosome biogenesis with roles for sphingolipid metabolites and enzymes spanning from the initial step of de novo ceramide synthesis to the sphingosine-1-phosphate lyase 1-mediated exit from the sphingolipid pathway...
2018: Advances in Cancer Research
Antonio Gomez-Muñoz
Ceramide 1-phosphate (C1P) is a pleiotropic bioactive sphingolipid metabolite capable of regulating key physiologic cell functions and promoting pathologic processes. Concerning pathology, C1P or ceramide kinase (CerK), the enzyme responsible for its biosynthesis in mammalian cells, has been implicated in cancer cell growth, survival, and dissemination and is involved in inflammatory responses associated with different types of cancer cells. The mechanisms or signaling pathways mediating these C1P actions have only been partially described...
2018: Advances in Cancer Research
Kristen A Jeffries, Natalia I Krupenko
Ceramides, important players in signal transduction, interact with multiple cellular pathways, including p53 pathways. However, the relationship between ceramide and p53 is very complex, and mechanisms underlying their coregulation are diverse and not fully characterized. The role of p53, an important cellular regulator and a transcription factor, is linked to its tumor suppressor function. Ceramides are involved in the regulation of fundamental processes in cancer cells including cell death, proliferation, autophagy, and drug resistance...
2018: Advances in Cancer Research
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