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Ceramide synthases

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https://www.readbyqxmd.com/read/29345004/epidermal-permeability-barrier-function-and-sphingolipid-content-in-the-skin-of-sphingomyelin-synthase-2-deficient-mice
#1
Koji Nomoto, Yurina Itaya, Ken Watanabe, Tadashi Yamashita, Toshiro Okazaki, Yoshihiro Tokudome
BACKGROUND: Sphingomyelin synthase (SMS) is an enzyme that generates sphingomyelin (SM) from ceramide (CER) and phosphatidylcholine. SM in the epidermis is a precursor of CER, an important lipid for epidermal permeability barrier function. However, the physiological role of SMS in skin is unclear. OBJECTIVES: To uncover the function of SMS in skin, we investigated sphingolipid metabolism enzyme activity in skin, SM content in the epidermis, CER content in the stratum corneum (SC) and transepidermal water loss (TEWL) as an indicator of barrier function in SMS2-knockout (KO) mice...
January 17, 2018: Experimental Dermatology
https://www.readbyqxmd.com/read/29343457/sphingolipid-signaling-in-renal-fibrosis
#2
REVIEW
Andrea Huwiler, Josef Pfeilschifter
Over the last decade, various sphingolipid subspecies have gained increasing attention as important signaling molecules that regulate a multitude of physiological and pathophysiological processes including inflammation and tissue remodeling. These mediators include ceramide, sphingosine 1-phosphate (S1P), the cerebroside glucosylceramide, lactosylceramide, and the gangliosides GM3 and Gb3. These lipids have been shown to accumulate in various chronic kidney diseases that typically end in renal fibrosis and ultimately renal failure...
January 14, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29329781/dopamine-transporter-trafficking-is-regulated-by-neutral-sphingomyelinase-2-ceramide-kinase
#3
Jong Hoon Won, Seok Kyun Kim, In Chul Shin, Hae Chan Ha, Ji Min Jang, Moon Jung Back, Dae Kyong Kim
Dopamine (DA) reuptake is the primary mechanism to terminate dopaminergic transmission in the synaptic cleft. The dopamine transporter (DAT) has an important role in the regulation of DA reuptake. This study provides anatomical and physiological evidence that DAT recycling is regulated by ceramide kinase via the sphingomyelin pathway. First, the results show that DAT and neutral sphingomyelinase 2 (nSMase2) were successfully co-precipitated from striatal samples and were colocalized in the mouse striatum or PC12 cells...
January 9, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29322079/fibroblast-and-keratinocyte-gene-expression-following-exposure-to-extracts-of-neem-plant-azadirachta-indica
#4
Takao Someya, Katsura Sano, Kotaro Hara, Yoshimasa Sagane, Toshihiro Watanabe, R G S Wijesekara
This data article provides gene expression profiles, determined by using real-time PCR, of fibroblasts and keratinocytes treated with 0.01% and 0.001% extracts of neem plant (Azadirachta indica), local name "Kohomba" in Sri Lanka, harvested in Sri Lanka. For fibroblasts, the dataset includes expression profiles for genes encoding hyaluronan synthase 1 (HAS1), hyaluronan synthase 2 (HAS2), hyaluronidase-1 (HYAL1), hyaluronidase-2 (HYAL2), versican, aggrecan, CD44, collagen, type I, alpha 1 (COL1A1), collagen, type III, alpha 1 (COL3A1), collagen, type VII, alpha 1 (COL7A1), matrix metalloproteinase 1 (MMP1), acid ceramidase, basic fibroblast growth factor (bFGF), fibroblast growth factor-7 (FGF7), vascular endothelial growth factor (VEGF), interleukin-1 alpha (IL-1α), cyclooxygenase-2 (cox2), transforming growth factor beta (TGF-β), and aquaporin 3 (AQP3)...
February 2018: Data in Brief
https://www.readbyqxmd.com/read/29321137/novel-function-of-ceramide-for-regulation-of-mitochondrial-atp-release-in-astrocytes
#5
Ji-Na Kong, Zhihui Zhu, Yutaka Itokazu, Guanghu Wang, Michael B Dinkins, Liansheng Zhong, Hsuan-Pei Lin, Ahmed Elsherbini, Silvia Leanhart, Xue Jiang, Haiyan Qin, Wenbo Zhi, Stefka D Spassieva, Erhard Bieberich
We reported that amyloid beta peptide (Abeta42) activated neutral sphingomyelinase 2 (nSMase2) thereby increasing the concentration of the sphingolipid ceramide in astrocytes. Here, we show that Abeta42 induced mitochondrial fragmentation in wild type astrocytes, but not in nSMase2-deficient cells or astrocytes treated with Fumonisin B1 (FB1), an inhibitor of ceramide synthases. Unexpectedly, ceramide depletion was concurrent with rapid movements of mitochondria, indicating an unknown function of ceramide for mitochondria...
January 10, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29274292/butyrate-and-docosahexaenoic-acid-interact-in-alterations-of-specific-lipid-classes-in-differentiating-colon-cancer-cells
#6
Zuzana Tylichová, Josef Slavík, Miroslav Ciganek, Petra Ovesná, Pavel Krčmář, Nicol Straková, Miroslav Machala, Alois Kozubík, Jiřina Hofmanová, Jan Vondráček
Docosahexaenoic acid (DHA) and sodium butyrate (NaBt) exhibit a number of interactive effects on colon cancer cell growth, differentiation or apoptosis; however, the molecular mechanisms responsible for these interactions and their impact on cellular lipidome are still not fully clear. Here, we show that both dietary agents together induce dynamic alterations of lipid metabolism, specific cellular lipid classes and fatty acid composition. In HT-29 cell line, a model of differentiating colon carcinoma cells, NaBt supported incorporation of free DHA into non-polar lipids and their accumulation in cytoplasmic lipid droplets...
December 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29229477/puma-dependent-mitophagy-by-abrus-agglutinin-contributes-to-apoptosis-through-ceramide-generation
#7
Prashanta Kumar Panda, Prajna Paramita Naik, Biswa Ranjan Meher, Durgesh Nandini Das, Subhadip Mukhopadhyay, Prakash Priyadharshi Praharaj, Tapas K Maiti, Sujit K Bhutia
PUMA, a BH3-only pro-apoptotic Bcl2 family protein, is known to translocate from the cytosol into the mitochondria in order to induce apoptosis. Interestingly, the induction of PUMA by p53 plays a critical role in DNA damage-induced apoptosis. In this study, we report mitophagy inducing potential of PUMA triggered by phytolectin Abrus agglutinin (AGG) in U87MG glioblastoma cells and established AGG-induced ceramide acts as the chief mediator of mitophagy dependent cell death through activation of both mitochondrial ROS as well as ER stress...
December 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29215176/protective-role-of-the-hog-pathway-against-the-growth-defect-caused-by-impaired-biosynthesis-of-complex-sphingolipids-in-yeast-saccharomyces-cerevisiae
#8
Yutaro Yamaguchi, Yuka Katsuki, Seiya Tanaka, Ryotaro Kawaguchi, Hiroto Denda, Takuma Ikeda, Kouichi Funato, Motohiro Tani
Complex sphingolipids play critical roles in various cellular events in the yeast Saccharomyces cerevisiae. To identify genes that are related to the growth defect caused by disruption of complex sphingolipid biosynthesis, we screened for suppressor mutations and multicopy suppressor genes that confer resistance against repression of AUR1 encoding inositol phosphorylceramide synthase. From the results of this screening, we found that the activation of high-osmolarity glycerol (HOG) pathway is involved in suppression of growth defect caused by impaired biosynthesis of complex sphingolipids...
December 7, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/29214724/cme-1-a-novel-polysaccharide-suppresses-inos-expression-in-lipopolysaccharide-stimulated-macrophages-through-ceramide-initiated-protein-phosphatase-2a-activation
#9
Joen-Rong Sheu, Zhih-Cherng Chen, Ming-Jen Hsu, Shwu-Huey Wang, Kuo-Wei Jung, Wei-Fan Wu, Szu-Han Pan, Ruei-Dun Teng, Chih-Hao Yang, Cheng-Ying Hsieh
CME-1, a novel water-soluble polysaccharide purified from Ophiocordyceps sinensis mycelia, has anti-oxidative, antithrombotic and antitumour properties. In this study, other major attributes of CME-1, namely anti-inflammatory and immunomodulatory properties, were investigated. Treating lipopolysaccharide (LPS)-stimulated RAW 264.7 cells with CME-1 concentration-dependently suppressed nitric oxide formation and inducible nitric oxide synthase (iNOS) expression. In the CME-1-treated RAW 264.7 cells, LPS-induced IκBα degradation and the phosphorylation of p65, Akt and mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase, c-Jun N-terminal kinase and p38, were reduced...
December 7, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29196503/sphingolipid-regulation-of-lung-epithelial-cell-mitophagy-and-necroptosis-during-cigarette-smoke-exposure
#10
Kenji Mizumura, Matthew J Justice, Kelly S Schweitzer, Sheila Krishnan, Irina Bronova, Evgeny V Berdyshev, Walter C Hubbard, Yael Pewzner-Jung, Anthony H Futerman, Augustine M K Choi, Irina Petrache
The mechanisms by which lung structural cells survive toxic exposures to cigarette smoke (CS) are not well defined but may involve proper disposal of damaged mitochondria by macro-autophagy (mitophagy), processes that may be influenced by pro-apoptotic ceramide (Cer) or its precursor dihydroceramide (DHC). Human lung epithelial and endothelial cells exposed to CS exhibited mitochondrial damage, signaled by phosphatase and tensin homolog-induced putative kinase 1 (PINK1) phosphorylation, autophagy, and necroptosis...
December 1, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29163475/critical-role-for-very-long-chain-sphingolipids-in-invariant-natural-killer-t-cell-development-and-homeostasis
#11
Ashish Saroha, Yael Pewzner-Jung, Natalia S Ferreira, Piyush Sharma, Youenn Jouan, Samuel L Kelly, Ester Feldmesser, Alfred H Merrill, François Trottein, Christophe Paget, Karl S Lang, Anthony H Futerman
The role of sphingolipids (SLs) in the immune system has come under increasing scrutiny recently due to the emerging contributions that these important membrane components play in regulating a variety of immunological processes. The acyl chain length of SLs appears particularly critical in determining SL function. Here, we show a role for very-long acyl chain SLs (VLC-SLs) in invariant natural killer T (iNKT) cell maturation in the thymus and homeostasis in the liver. Ceramide synthase 2-null mice, which lack VLC-SLs, were susceptible to a hepatotropic strain of lymphocytic choriomeningitis virus, which is due to a reduction in the number of iNKT cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29138469/adoptive-transfer-of-ceramide-synthase-6-deficient-splenocytes-reduces-the-development-of-colitis
#12
Matthew J Scheffel, Kristi Helke, Ping Lu, Jacob S Bowers, Besim Ogretmen, Elizabeth Garrett-Mayer, Chrystal M Paulos, Christina Voelkel-Johnson
Sphingolipids regulate critical cellular processes including inflammation. Ceramide, which serves a central role in sphingolipid metabolism, is generated by six ceramide synthases (CerS) that differ in substrate specificity. CerS6 preferentially generates C16-ceramide and its mRNA is highly expressed in immune tissues. In this study we analyzed how deficiency of CerS6 impacts on the development of colitis using an adoptive transfer model. Adoptive transfer of CerS6-deficient splenocytes, which have significantly decreased levels of C16-ceramide, showed that CerS6-deficiency protected against the development of colitis...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29133339/decreased-ceramide-underlies-mitochondrial-dysfunction-in-charcot-marie-tooth-2f
#13
Nicholas U Schwartz, Ryan W Linzer, Jean-Philip Truman, Mikhail Gurevich, Yusuf A Hannun, Can E Senkal, Lina M Obeid
Charcot-Marie-Tooth (CMT) disease is the most commonly inherited neurologic disorder, but its molecular mechanisms remain unclear. One variant of CMT, 2F, is characterized by mutations in heat shock protein 27 (Hsp27). As bioactive sphingolipids have been implicated in neurodegenerative diseases, we sought to determine if their dysregulation is involved in CMT. Here, we show that Hsp27 knockout mice demonstrated decreases in ceramide in peripheral nerve tissue and that the disease-associated Hsp27 S135F mutant demonstrated decreases in mitochondrial ceramide...
November 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29127192/lipotoxic-very-long-chain-ceramides-cause-mitochondrial-dysfunction-oxidative-stress-and-cell-death-in-cardiomyocytes
#14
Brittany A Law, Xianghai Liao, Kelsey S Moore, Abigail Southard, Patrick Roddy, Ruiping Ji, Zdzislaw Sculz, Ala Bielawska, P Christian Schulze, L Ashley Cowart
Accumulating data support a role for bioactive lipids as mediators of lipotixicity in cardiomyocytes. One class of these, the ceramides, constitutes a family of molecules that differ in structure and are synthesized by distinct enzymes, ceramide synthase (CerS)1-CerS6. Data support that specific ceramides and the enzymes that catalyze their formation play distinct roles in cell function. In a mouse model of diabetic cardiomyopathy, sphingolipid profiling revealed increases in not only the CerS5-derived ceramides but also in very long chain (VLC) ceramides derived from CerS2...
November 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29121774/sphingolipids-and-redox-signaling-in-renal-regulation-and-chronic-kidney-diseases
#15
Owais M Bhat, Xinxu Yuan, Guangbi Li, RaMi Lee, Pin Lan Li
SIGNIFICANCE: Sphingolipids play critical roles in the membrane biology and intracellular signaling events that influence cellular behavior and function. Our review focuses on the cellular mechanisms and functional relevance of the cross talk between sphingolipids and redox signaling, which may be critically implicated in the pathogenesis of different renal diseases. Recent Advances: Reactive oxygen species (ROS) and sphingolipids can regulate cellular redox homeostasis through the regulation of NADPH oxidase, mitochondrial integrity, nitric oxide synthase (NOS) and antioxidant enzymes...
November 9, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29109103/hepatocyte-nuclear-factor-1a-deficiency-causes-hemolytic-anemia-in-mice-by-altering-erythrocyte-sphingolipid-homeostasis
#16
Karin von Wnuck Lipinski, Sarah Weske, Petra Keul, Susann Peters, Hideo A Baba, Gerd Heusch, Markus H Gräler, Bodo Levkau
The Hepatocyte Nuclear Factor (HNF) family regulates complex networks of metabolism and organ development. Human mutations in its prototypical member HNF1A cause maturity-onset of diabetes of the young (MODY) type 3. In this study, we identified an important role for HNF1A in the preservation of erythrocyte membrane integrity, calcium homeostasis and osmotic resistance through a yet unrecognized link of HNF1A to sphingolipid homeostasis. HNF1A(-/-) mice displayed microcytic hypochromic anemia with reticulocytosis that was partially compensated by avid extramedullary erythropoiesis at all erythroid stages in the spleen thereby excluding erythroid differentiation defects...
November 6, 2017: Blood
https://www.readbyqxmd.com/read/29097114/endoplasmic-reticulum-stress-mediated-autophagy-activation-attenuates-fumonisin-b1-induced-hepatotoxicity-in-vitro-and-in-vivo
#17
Mahendra Pal Singh, Sun Chul Kang
Although pathological characteristics of fumonisin B1 are known to induce hepatic injury over prolonged periods, the cellular defense mechanisms against the detrimental effects of FB1 are still unknown. The underlying mechanisms of FB1 toxicity are thought to be related with the inhibition of ceramide synthase, causing an accumulation of sphingoid bases, which in turn cause development of oxidative stress. Herein, we investigated whether autophagy, a cellular defense mechanism, protects liver cells from FB1 exposure...
October 31, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29089614/obesity-induced-changes-in-lipid-mediators-persist-after-weight-loss
#18
A Hernandez-Carretero, N Weber, M R La Frano, W Ying, J L Rodriguez, D D Sears, V Wallenius, E Börgeson, J W Newman, O Osborn
BACKGROUND: Obesity induces significant changes in lipid mediators, however, the extent to which these changes persist after weight loss has not been investigated. SUBJECTS/METHODS: We fed C57BL6 mice a high fat diet to generate obesity and then switched the diet to a lower fat diet to induce weight loss. We performed a comprehensive metabolic profiling of lipid mediators including oxylipins, endocannabinoids, sphingosines and ceramides in key metabolic tissues including adipose, liver, muscle, hypothalamus and plasma...
November 1, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29066540/tgf-%C3%AE-receptor-i-ii-trafficking-and-signaling-at-primary-cilia-are-inhibited-by-ceramide-to-attenuate-cell-migration-and-tumor-metastasis
#19
Salih Gencer, Natalia Oleinik, Jisun Kim, Shanmugam Panneer Selvam, Ryan De Palma, Mohammed Dany, Rose Nganga, Raquela J Thomas, Can E Senkal, Philip H Howe, Besim Ogretmen
Signaling by the transforming growth factor-β (TGF-β) receptors I and II (TβRI/II) and the primary cilia-localized sonic hedgehog (Shh) pathway promote cell migration and, consequently, tumor metastasis. In contrast, the sphingolipid ceramide inhibits cell proliferation and tumor metastasis. We investigated whether ceramide metabolism inhibited TβRI/II trafficking to primary cilia to attenuate cross-talk between TβRI/II and the Shh pathway. We found that ceramide synthase 4 (CerS4)-generated ceramide stabilized the association between TβRI and the inhibitory factor Smad7, which limited the trafficking of TβRI/II to primary cilia...
October 24, 2017: Science Signaling
https://www.readbyqxmd.com/read/29050963/long-chain-glucosylceramides-crosstalk-with-lyn-mediates-endometrial-cell-migration
#20
Dulani Wimalachandra, Joan Xiaohui Yang, Lina Zhu, Evan Tan, Harry Asada, Jerry Y K Chan, Yie Hou Lee
Endometriosis is a disease characterized by regurgitated lesions which are invasive and migratory, embedding at ectopic, extra-uterine locations. Extracellular glucosylceramides (GlcCers), bioactive sphingolipids potentiating signals for cell migration, are found in elevated levels in endometriosis; however underlying mechanisms that result in cellular migration are poorly defined. Here, we demonstrated that internalized GlcCer induced migratory activity in immortalized human endometrial stromal cells (HESCs), with highest potency observed in long-chain GlcCer...
October 16, 2017: Biochimica et Biophysica Acta
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