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https://www.readbyqxmd.com/read/29970615/an-oxanthroquinone-derivative-that-disrupts-ras-plasma-membrane-localization-inhibits-cancer-cell-growth
#1
Lingxiao Tan, Kwang-Jin Cho, Pratik Neupane, Robert J Capon, John F Hancock
Oncogenic RAS proteins are commonly expressed in human cancer. To be functional, RAS proteins must undergo post-translational modification and localize to the plasma membrane (PM). Therefore, compounds that prevent RAS PM targeting have potential as putative RAS inhibitors. Here we examine the mechanism of action of oxanthroquinone G01 (G01), a recently described inhibitor of KRAS PM localization. We show that G01 mislocalizes HRAS and KRAS from the PM with similar potency and disrupts the spatial organization of RAS proteins remaining on the PM...
July 3, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29876372/fibroblast-and-keratinocyte-gene-expression-following-exposure-to-the-extracts-of-holy-basil-plant-ocimum-tenuiflorum-malabar-nut-plant-justicia-adhatoda-and-emblic-myrobalan-plant-phyllanthus-emblica
#2
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 holy basil plant ( Ocimum tenuiflorum ), sri lankan local name "maduruthala", 0.1% and 0.01% extracts of malabar nut plant ( Justicia adhatoda ), sri lankan local name "adayhoda" and 0.003% and 0.001% extracts of emblic myrobalan plant ( Phyllanthus emblica ), sri lankan local name "nelli", 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)...
April 2018: Data in Brief
https://www.readbyqxmd.com/read/29746165/a-lysosome-plasma-membrane-sphingolipid-axis-linking-lysosomal-storage-to-cell-growth-arrest
#3
Maura Samarani, Nicoletta Loberto, Giulia Soldà, Letizia Straniero, Rosanna Asselta, Stefano Duga, Giulia Lunghi, Fabio A Zucca, Laura Mauri, Maria Grazia Ciampa, Domitilla Schiumarini, Rosaria Bassi, Paola Giussani, Elena Chiricozzi, Alessandro Prinetti, Massimo Aureli, Sandro Sonnino
Lysosomal accumulation of undegraded materials is a common feature of lysosomal storage diseases, neurodegenerative disorders, and the aging process. To better understand the role of lysosomal storage in the onset of cell damage, we used human fibroblasts loaded with sucrose as a model of lysosomal accumulation. Sucrose-loaded fibroblasts displayed increased lysosomal biogenesis followed by arrested cell proliferation. Notably, we found that reduced lysosomal catabolism and autophagy impairment led to an increase in sphingolipids ( i...
May 10, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29673590/the-cross-roles-of-sphingosine-kinase-1-2-and-ceramide-glucosyltransferase-in-cell-growth-and-death
#4
Jingdong Qin, John P Kilkus, Glyn Dawson
Sphingosine-1-phosphate is synthesized by two sphingosine kinases, cytosolic SK1 and nuclear SK2 but SK2 expression was much higher than SK1in mouse skin fibroblasts. However, in SK2-/- cells, SK1 expression was markedly increased to SK2 levels whereas in SK1-/- cells, SK2 expression was unaffected. Ceramide, glucosylceramide and sphingosine levels were all increased in SK1-/- but less so in SK2-/- cells and S1P levels were not significantly reduced in either SK1-/- or SK2-/- cells. Greatly increased Ceramide glucosyltransferase expression was observed in SK1-/- cells but less so in SK2-/- cells suggested a role in drug resistance...
June 7, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29580926/19q13-12-microdeletion-syndrome-fibroblasts-display-abnormal-storage-of-cholesterol-and-sphingolipids-in-the-endo-lysosomal-system
#5
Kexin Zhao, Aarnoud van der Spoel, Claudia Castiglioni, Sarah Gale, Hideji Fujiwara, Daniel S Ory, Neale D Ridgway
Microdeletions in 19q12q13.12 cause a rare and complex haploinsufficiency syndrome characterized by intellectual deficiency, developmental delays, and neurological movement disorders. Variability in the size and interval of the deletions makes it difficult to attribute the complex clinical phenotype of this syndrome to an underlying gene(s). As an alternate approach, we examined the biochemical and metabolic features of fibroblasts from an affected individual to derive clues as to the molecular basis for the syndrome...
June 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29428730/targeting-sphingosine-kinase-2-by-abc294640-inhibits-human-skin-squamous-cell-carcinoma-cell-growth
#6
Jianbo Zhou, Jin Chen, Huanmiao Yu
The activity of ABC294640, a small-molecular sphingosine kinase 2 (SphK2) inhibitor, in human skin squamous cell carcinoma (SCC) cells was tested in this study. SphK2 mRNA and protein are expressed in established (A431 cheilocarcinoma cell line) and primary human skin SCC cells. ABC294640 dose-dependently inhibited survival, cell cycle progression and proliferation of skin SCC cells. Furthermore, ABC294640 induced caspase-3/-9 and apoptosis activation in skin SCC cells. The SphK2 inhibitor was however non-cytotoxic to SphK2-null skin melanocytes, keratinocytes and fibroblasts...
March 4, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29404440/engineered-fgf19-eliminates-bile-acid-toxicity-and-lipotoxicity-leading-to-resolution-of-steatohepatitis-and-fibrosis-in-mice
#7
Mei Zhou, R Marc Learned, Stephen J Rossi, Alex M DePaoli, Hui Tian, Lei Ling
Nonalcoholic fatty liver disease (NAFLD) is an increasingly prevalent chronic liver disease for which no approved therapies are available. Despite intensive research, the cellular mechanisms that mediate NAFLD pathogenesis and progression are poorly understood. Although obesity, diabetes, insulin resistance, and related metabolic syndrome, all consequences of a Western diet lifestyle, are well-recognized risk factors for NAFLD development, dysregulated bile acid metabolism is emerging as a novel mechanism contributing to NAFLD pathogenesis...
December 2017: Hepatology Communications
https://www.readbyqxmd.com/read/29396028/cutis-laxa-exocrine-pancreatic-insufficiency-and-altered-cellular-metabolomics-as-additional-symptoms-in-a-new-patient-with-atp6ap1-cdg
#8
Bianca Dimitrov, Nastassja Himmelreich, Agnes L Hipgrave Ederveen, Christian Lüchtenborg, Jürgen G Okun, Maximilian Breuer, Anna-Marlen Hutter, Matthias Carl, Luca Guglielmi, Andrea Hellwig, Kai Christian Thiemann, Markus Jost, Verena Peters, Christian Staufner, Georg F Hoffmann, Annette Hackenberg, Nagarajan Paramasivam, Stefan Wiemann, Roland Eils, Matthias Schlesner, Sabine Strahl, Britta Brügger, Manfred Wuhrer, G Christoph Korenke, Christian Thiel
Congenital disorders of glycosylation (CDG) are genetic defects in the glycoconjugate biosynthesis. >100 types of CDG are known, most of them cause multi-organ diseases. Here we describe a boy whose leading symptoms comprise cutis laxa, pancreatic insufficiency and hepatosplenomegaly. Whole exome sequencing identified the novel hemizygous mutation c.542T>G (p.L181R) in the X-linked ATP6AP1, an accessory protein of the mammalian vacuolar H+ -ATPase, which led to a general N-glycosylation deficiency. Studies of serum N-glycans revealed reduction of complex sialylated and appearance of truncated diantennary structures...
March 2018: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29322079/fibroblast-and-keratinocyte-gene-expression-following-exposure-to-extracts-of-neem-plant-azadirachta-indica
#9
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/29211351/application-of-fourier-transform-infrared-spectroscopy-to-biomolecular-profiling-of-cultured-fibroblast-cells-from-gaucher-disease-patients-a-preliminary-investigation
#10
Nasit Igci, Parisa Sharafi, Duygu Ozel Demiralp, Cemil Ozerk Demiralp, Aysel Yuce, Serap Dokmeci Emre
BACKGROUND: Gaucher disease (GD) is defined as an autosomal recessive disorder resulting from the deficiency of glucocerebrosidase (E.C. 3.2.1.45). Glucocerebrosidase is responsible for the degradation of glucosylceramide into ceramide and glucose. The deficiency of this enzyme results in the accumulation of undegraded glucosylceramide, almost exclusively in macrophages. With Fourier transform infrared (FTIR) spectroscopy, the complete molecular diversity of the samples can be studied comparatively and the amount of the particular materials can be determined...
October 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29130419/recapitulation-of-native-dermal-tissue-in-a-full-thickness-human-skin-model-using-human-collagens
#11
Arnout Mieremet, Marion Rietveld, Rianne van Dijk, Joke A Bouwstra, Abdoelwaheb El Ghalbzouri
OBJECTIVE: Full-thickness skin models comprise a three-dimensional dermal equivalent based on an animal-derived collagen matrix that harbors fibroblasts and an epidermal equivalent formed by keratinocytes. The functionality of both equivalents is influenced by many factors, including extracellular matrix composition and resident cell type. Animal-derived collagens differ in amino acid composition and physicochemical properties from human collagens. This composition could alter the functionality of the dermal equivalent and epidermal morphogenesis with the barrier formation in full-thickness models (FTMs)...
June 2018: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28827783/ccdc3-a-new-p63-target-involved-in-regulation-of-liver-lipid-metabolism
#12
Wenjuan Liao, Hongbing Liu, Yiwei Zhang, Ji Hoon Jung, Jiaxiang Chen, Xiaohua Su, Yeong C Kim, Elsa R Flores, San Ming Wang, Malwina Czarny-Ratajczak, Wen Li, Shelya X Zeng, Hua Lu
TAp63, a member of the p53 family, has been shown to regulate energy metabolism. Here, we report coiled coil domain-containing 3 (CCDC3) as a new TAp63 target. TAp63, but not ΔNp63, p53 or p73, upregulates CCDC3 expression by directly binding to its enhancer region. The CCDC3 expression is markedly reduced in TAp63-null mouse embryonic fibroblasts and brown adipose tissues and by tumor necrosis factor alpha that reduces p63 transcriptional activity, but induced by metformin, an anti-diabetic drug that activates p63...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28775166/aneuploid-cell-survival-relies-upon-sphingolipid-homeostasis
#13
Yun-Chi Tang, Hui Yuwen, Kaiying Wang, Peter M Bruno, Kevin Bullock, Amy Deik, Stefano Santaguida, Marianna Trakala, Sarah J Pfau, Na Zhong, Tao Huang, Lan Wang, Clary B Clish, Michael T Hemann, Angelika Amon
Aneuploidy, a hallmark of cancer cells, poses an appealing opportunity for cancer treatment and prevention strategies. Using a cell-based screen to identify small molecules that could selectively kill aneuploid cells, we identified the compound N -[2-hydroxy-1-(4-morpholinylmethyl)-2-phenylethyl]-decanamide monohydrochloride (DL-PDMP), an antagonist of UDP-glucose ceramide glucosyltransferase. DL-PDMP selectively inhibited proliferation of aneuploid primary mouse embryonic fibroblasts and aneuploid colorectal cancer cells...
October 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28379166/phospholipase-d-from-loxosceles-laeta-spider-venom-induces-il-6-il-8-cxcl1-gro-%C3%AE-and-ccl2-mcp-1-production-in-human-skin-fibroblasts-and-stimulates-monocytes-migration
#14
José M Rojas, Tomás Arán-Sekul, Emmanuel Cortés, Romina Jaldín, Kely Ordenes, Patricio R Orrego, Jorge González, Jorge E Araya, Alejandro Catalán
Cutaneous loxoscelism envenomation by Loxosceles spiders is characterized by the development of a dermonecrotic lesion, strong inflammatory response, the production of pro-inflammatory mediators, and leukocyte migration to the bite site. The role of phospholipase D (PLD) from Loxosceles in the recruitment and migration of monocytes to the envenomation site has not yet been described. This study reports on the expression and production profiles of cytokines and chemokines in human skin fibroblasts treated with catalytically active and inactive recombinant PLDs from Loxosceles laeta (rLlPLD) and lipid inflammatory mediators ceramide 1-phosphate (C1P) and lysophosphatidic acid (LPA), and the evaluation of their roles in monocyte migration...
April 5, 2017: Toxins
https://www.readbyqxmd.com/read/28275553/enzyme-replacement-therapy-for-farber-disease-proof-of-concept-studies-in-cells-and-mice
#15
Xingxuan He, Shaalee Dworski, Changzhi Zhu, Victor DeAngelis, Alex Solyom, Jeffrey A Medin, Calogera M Simonaro, Edward H Schuchman
A series of studies were carried out in Farber disease (OMIM #228000) cells and mice to evaluate the feasibility of enzyme replacement therapy (ERT) for this disorder. Media from Chinese hamster ovary (CHO) cells overexpressing human recombinant acid ceramidase (rhAC) was used to treat fibroblasts from a Farber disease patient, leading to significantly reduced ceramide. We also found that chondrocytes from Farber disease mice had a markedly abnormal chondrogenic phenotype, and this was corrected by rhAC as well...
June 2017: BBA Clinical
https://www.readbyqxmd.com/read/28188148/analysis-of-sphingolipids-in-human-corneal-fibroblasts-from-normal-and-keratoconus-patients
#16
Hui Qi, Shrestha Priyadarsini, Sarah E Nicholas, Akhee Sarker-Nag, Jeremy Allegood, Charles E Chalfant, Nawajes A Mandal, Dimitrios Karamichos
The pathophysiology of human keratoconus (KC), a bilateral progressive corneal disease leading to protrusion of the cornea, stromal thinning, and scarring, is not well-understood. In this study, we investigated a novel sphingolipid (SPL) signaling pathway through which KC may be regulated. Using human corneal fibroblasts (HCFs) and human KC cells (HKCs), we examined the SPL pathway modulation. Both cell types were stimulated by the three transforming growth factor (TGF)-β isoforms: TGF-β1 (T1), TGF-β2 (T2), and TGF-β3 (T3)...
April 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28019653/mactosylceramide-prevents-glial-cell-overgrowth-by-inhibiting-insulin-and-fibroblast-growth-factor-receptor-signaling
#17
Stine Gerdøe-Kristensen, Viktor K Lund, Hans H Wandall, Ole Kjaerulff
Receptor tyrosine kinase (RTK) signaling controls key aspects of cellular differentiation, proliferation, survival, metabolism, and migration. Deregulated RTK signaling also underlies many cancers. Glycosphingolipids (GSL) are essential elements of the plasma membrane. By affecting clustering and activity of membrane receptors, GSL modulate signal transduction, including that mediated by the RTK. GSL are abundant in the nervous system, and glial development in Drosophila is emerging as a useful model for studying how GSL modulate RTK signaling...
November 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27869314/runx1-orchestrates-sphingolipid-metabolism-and-glucocorticoid-resistance-in-lymphomagenesis
#18
A Kilbey, A Terry, S Wotton, G Borland, Q Zhang, N Mackay, A McDonald, M Bell, M J O Wakelam, E R Cameron, J C Neil
The three-membered RUNX gene family includes RUNX1, a major mutational target in human leukemias, and displays hallmarks of both tumor suppressors and oncogenes. In mouse models, the Runx genes appear to act as conditional oncogenes, as ectopic expression is growth suppressive in normal cells but drives lymphoma development potently when combined with over-expressed Myc or loss of p53. Clues to underlying mechanisms emerged previously from murine fibroblasts where ectopic expression of any of the Runx genes promotes survival through direct and indirect regulation of key enzymes in sphingolipid metabolism associated with a shift in the "sphingolipid rheostat" from ceramide to sphingosine-1-phosphate (S1P)...
June 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27562995/-tumor-necrosis-fa%C3%B1-tor-alpha-potential-target-for-neuroprotector-dimebon
#19
A V Alessenko, S O Bachurin, S V Gurianova, Y O Karatasso, E F Shevtsova, L N Shingarova
Dimebon (Dimebolin) is an antihistamine drug which has been used in Russia since 1983. Recently Dimebolin has attracted renewed interest after being shown to have positive effects on persons suffering from Alzheimer's disease. Animal studies have shown that dimebon acts through multiple mechanisms, both blocking the action of neurotoxic beta-amyloid peptides and inhibiting L-type calcium channels, modulating the action of AMPA and NMDA glutamate receptors. Our experiments with cell culture L929 and mice have shown that dimebon may exert its neuroprotective effect by blocking cytotoxic signals induced by proinflammatory cytokines such as TNF-a which are believed to play a central role in Alzheimer's disease...
May 2016: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/27327378/incorporation-and-visualization-of-azido-functionalized-n-oleoyl-serinol-in-jurkat-cells-mouse-brain-astrocytes-3t3-fibroblasts-and-human-brain-microvascular-endothelial-cells
#20
T Walter, L Collenburg, L Japtok, B Kleuser, S Schneider-Schaulies, N Müller, J Becam, A Schubert-Unkmeir, J N Kong, E Bieberich, J Seibel
The synthesis and biological evaluation of azido-N-oleoyl serinol is reported. It mimicks biofunctional lipid ceramides and has shown to be capable of click reactions for cell membrane imaging in Jurkat and human brain microvascular endothelial cells.
June 30, 2016: Chemical Communications: Chem Comm
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