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[PMID]:28958935
[Au] Autor:Jin H; Wang C; Gu D; Zhang Y; Fan S; Xing S; Wang H; Ruan H; Yang C; Lv Y; Feng H; Yao M; Qin W
[Ad] Endereço:State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, China.
[Ti] Título:Liver-specific deletion of LASS2 delayed regeneration of mouse liver after partial hepatectomy.
[So] Source:Biochem Biophys Res Commun;493(3):1176-1183, 2017 Nov 25.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The capacity of liver regeneration is critical for patients with liver diseases. However, cellular and molecular mechanisms of liver regeneration are still incompletely defined. Here, we assessed roles of LASS2 in liver regeneration following partial hepatectomy (PHx) in mice. Our results showed that protein level of LASS2 remarkably increased during liver regeneration after PHx in wildtype (WT) mice. Comparing to WT mice, liver regeneration index after PHx was significantly decreased from day 1 to day 5 in liver-specific LASS2 knockout (LASS2-LKO) mice. Interestingly, liver mass of LASS2-LKO mice could sufficiently recover at day 14 after PHx. Immunohistochemistry (IHC) and western blot analyses revealed that proliferation markers, such as PCNA and Ki67, were potently reduced during liver regeneration in LASS2-LKO mice. In addition, several cell cycle related molecules, such as cyclin A, CDK2 and p-Rb, were decreased in LASS2-LKO mice after PHx. Co-immunoprecipitation assay further revealed a decreased formation of CDK4/cyclin D1 complex after PHx in LASS2-LKO mice. However, phosphorylation of Akt was significantly activated from day 2 after PHx in LASS2-LKO mice when compared with that in WT mice, which may explain the recovery of liver mass at the late stage of liver regeneration in LASS2-LKO mice. Taken together, we conclude that LASS2 plays an important role in efficient liver regeneration in response to PHx.
[Mh] Termos MeSH primário: Hepatectomia/métodos
Regeneração Hepática/fisiologia
Esfingosina N-Aciltransferase/genética
[Mh] Termos MeSH secundário: Animais
Ciclo Celular/fisiologia
Proliferação Celular
Tamanho Celular
Hepatócitos/citologia
Hepatócitos/metabolismo
Camundongos Knockout
Camundongos Transgênicos
Proteínas Proto-Oncogênicas c-akt/metabolismo
Esfingosina N-Aciltransferase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.3.1.24 (Cers2 protein, mouse); EC 2.3.1.24 (Sphingosine N-Acyltransferase); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170930
[St] Status:MEDLINE


  2 / 182 MEDLINE  
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[PMID]:28775166
[Au] Autor:Tang YC; Yuwen H; Wang K; Bruno PM; Bullock K; Deik A; Santaguida S; Trakala M; Pfau SJ; Zhong N; Huang T; Wang L; Clish CB; Hemann MT; Amon A
[Ad] Endereço:The Key Laboratory of Stem Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine, Shanghai, China. yctang@sibs.ac.cn
[Ti] Título:Aneuploid Cell Survival Relies upon Sphingolipid Homeostasis.
[So] Source:Cancer Res;77(19):5272-5286, 2017 Oct 01.
[Is] ISSN:1538-7445
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo: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 -[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. Its selective cytotoxic effects were based on further accentuating the elevated levels of ceramide, which characterize aneuploid cells, leading to increased apoptosis. We observed that DL-PDMP could also enhance the cytotoxic effects of paclitaxel, a standard-of-care chemotherapeutic agent that causes aneuploidy, in human colon cancer and mouse lymphoma cells. Our results offer pharmacologic evidence that the aneuploid state in cancer cells can be targeted selectively for therapeutic purposes, or for reducing the toxicity of taxane-based drug regimens. .
[Mh] Termos MeSH primário: Aneuploidia
Neoplasias Colorretais/patologia
Embrião de Mamíferos/citologia
Fibroblastos/citologia
Homeostase
Linfoma/patologia
Esfingolipídeos/metabolismo
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/farmacologia
Apoptose/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Células Cultivadas
Ceramidas/metabolismo
Neoplasias Colorretais/tratamento farmacológico
Neoplasias Colorretais/metabolismo
Sinergismo Farmacológico
Embrião de Mamíferos/efeitos dos fármacos
Embrião de Mamíferos/metabolismo
Feminino
Fibroblastos/efeitos dos fármacos
Fibroblastos/metabolismo
Glucosiltransferases/metabolismo
Seres Humanos
Linfoma/tratamento farmacológico
Linfoma/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Nus
Morfolinas/farmacologia
Esfingosina N-Aciltransferase/metabolismo
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Ceramides); 0 (Morpholines); 0 (Sphingolipids); EC 2.3.1.24 (Sphingosine N-Acyltransferase); EC 2.4.1.- (Glucosyltransferases); EC 2.4.1.80 (ceramide glucosyltransferase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170805
[St] Status:MEDLINE
[do] DOI:10.1158/0008-5472.CAN-17-0049


  3 / 182 MEDLINE  
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[PMID]:28551069
[Au] Autor:Dany M; Elston D
[Ad] Endereço:Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston, South Carolina.
[Ti] Título:Gene expression of sphingolipid metabolism pathways is altered in hidradenitis suppurativa.
[So] Source:J Am Acad Dermatol;77(2):268-273.e6, 2017 Aug.
[Is] ISSN:1097-6787
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Hidradenitis suppurativa (HS) is a debilitating skin disease characterized by painful recurrent nodules and abscesses caused by chronic inflammation. Early events in the development of HS are believed to occur in the folliculopilosebaceous unit; however, the signaling pathways behind this mechanism are unknown. Sphingolipids, such as ceramide, are essential components of the skin and appendages and have important structural and signaling roles. OBJECTIVE: We sought to explore whether the gene expression of enzymes involved in sphingolipid metabolic pathways is altered in HS. METHODS: A microarray data set including 30 samples was used to compare the expression of sphingolipid-related enzymes in inflammatory skin lesions from HS patients (n = 17) with the expression in clinically healthy skin tissue (n = 13). Differential expression of sphingolipid metabolism-related genes was analyzed using Gene Expression Omnibus 2R. RESULTS: HS lesional skin samples have significantly decreased expression of enzymes generating ceramide and sphingomyelin, increased expression of enzymes catabolizing ceramide to sphingosine, and increased expression of enzymes converting ceramide to galactosylceramide and gangliosides. LIMITATIONS: Limitations of this study include assessing the expression of sphingolipid-related enzymes without assessing the levels of the related sphingolipids. CONCLUSION: Our study suggests that sphingolipid metabolism is altered in HS lesional skin compared with normal skin.
[Mh] Termos MeSH primário: Expressão Gênica
Hidradenite Supurativa/enzimologia
Hidradenite Supurativa/genética
Perilipinas/genética
Pele/enzimologia
Esfingolipídeos/metabolismo
[Mh] Termos MeSH secundário: Ceramidase Alcalina/genética
Estudos de Casos e Controles
Ceramidas/metabolismo
Proteínas Quinases Dependentes de AMP Cíclico/genética
Glucosilceramidase/genética
Glucosiltransferases/genética
Glicoesfingolipídeos/metabolismo
Hexosaminidases/genética
Seres Humanos
Lisofosfolipídeos/metabolismo
Proteínas de Membrana/genética
Redes e Vias Metabólicas/genética
Fosfotransferases (Aceptor do Grupo Álcool)/genética
Serina C-Palmitoiltransferase/genética
Transdução de Sinais/genética
Esfingolipídeos/biossíntese
Esfingomielina Fosfodiesterase/genética
Esfingomielinas/metabolismo
Esfingosina/análogos & derivados
Esfingosina/metabolismo
Esfingosina N-Aciltransferase/genética
Proteínas Supressoras de Tumor/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ceramides); 0 (Glycosphingolipids); 0 (Lysophospholipids); 0 (Membrane Proteins); 0 (Perilipins); 0 (Sphingolipids); 0 (Sphingomyelins); 0 (Tumor Suppressor Proteins); 26993-30-6 (sphingosine 1-phosphate); EC 2.3.1.24 (CERS2 protein, human); EC 2.3.1.24 (CERS5 protein, human); EC 2.3.1.24 (Sphingosine N-Acyltransferase); EC 2.3.1.50 (Serine C-Palmitoyltransferase); EC 2.4.1.- (Glucosyltransferases); EC 2.4.1.80 (ceramide glucosyltransferase); EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor)); EC 2.7.1.91 (sphingosine kinase 2, human); EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases); EC 3.1.4.12 (Sphingomyelin Phosphodiesterase); EC 3.2.1.- (Hexosaminidases); EC 3.2.1.45 (Glucosylceramidase); EC 3.5.1.23 (Alkaline Ceramidase); NGZ37HRE42 (Sphingosine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170825
[Lr] Data última revisão:
170825
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170529
[St] Status:MEDLINE


  4 / 182 MEDLINE  
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[PMID]:28424433
[Au] Autor:Çoban N; Güçlü Geyik F; Yildirim Ö; Erginel Ünaltuna N
[Ad] Endereço:Department of Genetics, Istanbul University Aziz Sancar Experimental Medicine Research Institute, Istanbul, Turkey. neslic@istanbul.edu.tr.
[Ti] Título:[Investigating the role of ceramide metabolism-associated CERS5 (LASS5) gene in atherosclerosis pathogenesis in endothelial cells].
[Ti] Título:Seramid metabolizmasi ile iliskili CERS5 (LASS5) geninin endotel hücrelerinde ateroskleroz patogenezindeki rolünün arastirilmasi..
[So] Source:Turk Kardiyol Dern Ars;45(2):118-125, 2017 Mar.
[Is] ISSN:1308-4488
[Cp] País de publicação:Turkey
[La] Idioma:tur
[Ab] Resumo:OBJECTIVE: Ceramide, the backbone of sphingolipids, is the key component affecting atherosclerotic changes through its important second-messenger role. Previous studies have demonstrated protective role of AMP-activated protein kinase (AMPK) genes in regulating atherosclerosis and hypertension. Ceramide synthase 5 (LASS5 or CERS5) gene has function in de novo synthesis of ceramide, and has indirect effect on AMPK gene. Aim of the present study was to identify role of LASS5 gene in atherosclerosis. METHODS: LASS5 gene-specific small interfering RNA (siRNA)-mediated gene silencing was performed in human umbilical vein endothelial cells (HUVEC) and differential expression of LASS5, AMPK-alpha and AMPK-alpha target genes were analyzed. HUVEC cells were then treated with AMPK activator in order to examine relationship of change in gene expression levels to AMPK activity. RESULTS: Novel physiological function of LASS5 was identified. Downregulation of LASS5 was found to attenuate ceramide production and increase expression of some AMPK target genes in HUVEC. CONCLUSION: This is the first study to demonstrate that LASS5 was involved in negative regulation of atherosclerosis-related genes, such as AMPK-alpha. These preliminary findings provide insight into molecular mechanism of atherosclerosis and are important for development of potential therapeutic agents in the treatment of atherosclerosis.
[Mh] Termos MeSH primário: Aterosclerose/metabolismo
Células Endoteliais da Veia Umbilical Humana/metabolismo
Esfingosina N-Aciltransferase/metabolismo
[Mh] Termos MeSH secundário: Células Cultivadas
Regulação para Baixo/efeitos dos fármacos
Seres Humanos
RNA Interferente Pequeno/genética
RNA Interferente Pequeno/farmacologia
Esfingosina N-Aciltransferase/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Small Interfering); EC 2.3.1.24 (CERS5 protein, human); EC 2.3.1.24 (Sphingosine N-Acyltransferase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170421
[St] Status:MEDLINE
[do] DOI:10.5543/tkda.2016.82389


  5 / 182 MEDLINE  
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[PMID]:28405720
[Au] Autor:Oertel S; Scholich K; Weigert A; Thomas D; Schmetzer J; Trautmann S; Wegner MS; Radeke HH; Filmann N; Brüne B; Geisslinger G; Tegeder I; Grösch S
[Ad] Endereço:Institute of Clinical Pharmacology, Faculty of Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany.
[Ti] Título:Ceramide synthase 2 deficiency aggravates AOM-DSS-induced colitis in mice: role of colon barrier integrity.
[So] Source:Cell Mol Life Sci;74(16):3039-3055, 2017 Aug.
[Is] ISSN:1420-9071
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Loss of intestinal barrier functions is a hallmark of inflammatory bowel disease like ulcerative colitis. The molecular mechanisms are not well understood, but likely involve dysregulation of membrane composition, fluidity, and permeability, which are all essentially regulated by sphingolipids, including ceramides of different chain length and saturation. Here, we used a loss-of-function model (CerS2 and CerS2 mice) to investigate the impact of ceramide synthase 2, a key enzyme in the generation of very long-chain ceramides, in the dextran sodium salt (DSS) evoked model of UC. CerS2 mice developed more severe disease than CerS2 mice in acute DSS and chronic AOM/DSS colitis. Deletion of CerS2 strongly reduced very long-chain ceramides (Cer24:0, 24:1) but concomitantly increased long-chain ceramides and sphinganine in plasma and colon tissue. In naive CerS2 mice, the expression of tight junction proteins including ZO-1 was almost completely lost in the colon epithelium, leading to increased membrane permeability. This could also be observed in vitro in CerS2 depleted Caco-2 cells. The increase in membrane permeability in CerS2 mice did not manifest with apparent clinical symptoms in naive mice, but with slight inflammatory signs such as an increase in monocytes and IL-10. AOM/DSS and DSS treatment alone led to a further deterioration of membrane integrity and to severe clinical symptoms of the disease. This was associated with stronger upregulation of cytokines in CerS2 mice and increased infiltration of the colon wall by immune cells, particularly monocytes, CD4 and Th17 T-cells, and an increase in tumor burden. In conclusion, CerS2 is crucial for the maintenance of colon barrier function and epithelial integrity. CerS2 knockdown, and associated changes in several sphingolipids such as a drop in very long-chain ceramides/(dh)-ceramides, an increase in long-chain ceramides/(dh)-ceramides, and sphinganine in the colon, may weaken endogenous defense against the endogenous microbiome.
[Mh] Termos MeSH primário: Colite/genética
Colite/patologia
Colo/patologia
Deleção de Genes
Esfingosina N-Aciltransferase/genética
[Mh] Termos MeSH secundário: Animais
Células CACO-2
Permeabilidade da Membrana Celular
Colite/induzido quimicamente
Colite/imunologia
Colo/imunologia
Dextranos
Modelos Animais de Doenças
Seres Humanos
Imunidade Celular
Camundongos
Camundongos Endogâmicos C57BL
Permeabilidade
Interferência de RNA
RNA Interferente Pequeno/genética
Esfingolipídeos/análise
Esfingolipídeos/imunologia
Esfingosina N-Aciltransferase/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dextrans); 0 (RNA, Small Interfering); 0 (Sphingolipids); EC 2.3.1.24 (Cers2 protein, mouse); EC 2.3.1.24 (Sphingosine N-Acyltransferase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170822
[Lr] Data última revisão:
170822
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170414
[St] Status:MEDLINE
[do] DOI:10.1007/s00018-017-2518-9


  6 / 182 MEDLINE  
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[PMID]:28369933
[Au] Autor:Garbowska M; Lukaszuk B; Miklosz A; Wróblewski I; Kurek K; Ostrowska L; Chabowski A; Zendzian-Piotrowska M; Zalewska A
[Ad] Endereço:Department of Hygiene, Epidemiology and Ergonomics, Medical University of Bialystok, Bialystok, Poland.
[Ti] Título:Sphingolipids metabolism in the salivary glands of rats with obesity and streptozotocin induced diabetes.
[So] Source:J Cell Physiol;232(10):2766-2775, 2017 Oct.
[Is] ISSN:1097-4652
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Diabetes is considered a major public health problem affecting millions of individuals worldwide. Remarkably, scientific reports regarding salivary glands sphingolipid metabolism in diabetes are virtually non-existent. This is odd given the well-established link between the both in other tissues (e.g., skeletal muscles, liver) and the key role of these glands in oral health preservation. The aim of this paper is to examine sphingolipids metabolism in the salivary glands in (pre)diabetes (evoked by high fat diet feeding or streptozotocin). Wistar rats were allocated into three groups: control, HFD-, or STZ-diabetes. The content of major sphingolipid classes in the parotid (PSG) and submandibular (SMSG) glands was assessed via chromatography. Additionally, Western blot analyses were employed for the evaluation of key sphingolipid signaling pathway enzyme levels. No changes in ceramide content in the PSG were found, whereas an increase in ceramide concentration for SMSG of the STZ group was observed. This was accompanied by an elevation in SPT1 level. Probably also sphingomyelin hydrolysis was increased in the SMSG of the STZ-diabetic rats, since we observed a significant drop in the amount of SM. PSG and SMSG respond differently to (pre)diabetes, with clearer pattern presented by the later gland. An activation of sphingomyelin signaling pathway was observed in the course of STZ-diabetes, that is, metabolic condition with rapid onset/progression. Whereas, chronic HFD lead to an inhibition of sphingomyelin signaling pathway in the salivary glands (manifested in an inhibition of ceramide de novo synthesis and accumulation of S1P).
[Mh] Termos MeSH primário: Diabetes Mellitus Experimental/metabolismo
Diabetes Mellitus Tipo 1/metabolismo
Obesidade/metabolismo
Glândula Parótida/metabolismo
Esfingolipídeos/metabolismo
Estreptozocina
Glândula Submandibular/metabolismo
[Mh] Termos MeSH secundário: Animais
Ceramidas/metabolismo
Diabetes Mellitus Experimental/induzido quimicamente
Diabetes Mellitus Tipo 1/induzido quimicamente
Dieta Hiperlipídica
Resistência à Insulina
Lisofosfolipídeos/metabolismo
Masculino
Obesidade/complicações
Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo
Ratos Wistar
Transdução de Sinais
Esfingomielina Fosfodiesterase/metabolismo
Esfingosina/análogos & derivados
Esfingosina/metabolismo
Esfingosina N-Aciltransferase/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ceramides); 0 (Lysophospholipids); 0 (Sphingolipids); 26993-30-6 (sphingosine 1-phosphate); 5W494URQ81 (Streptozocin); EC 2.3.1.24 (Sphingosine N-Acyltransferase); EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor)); EC 2.7.1.- (sphingosine kinase); EC 3.1.4.12 (Sphingomyelin Phosphodiesterase); NGZ37HRE42 (Sphingosine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170404
[St] Status:MEDLINE
[do] DOI:10.1002/jcp.25939


  7 / 182 MEDLINE  
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[PMID]:28320857
[Au] Autor:Ferreira NS; Engelsby H; Neess D; Kelly SL; Volpert G; Merrill AH; Futerman AH; Færgeman NJ
[Ad] Endereço:From the Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel.
[Ti] Título:Regulation of very-long acyl chain ceramide synthesis by acyl-CoA-binding protein.
[So] Source:J Biol Chem;292(18):7588-7597, 2017 May 05.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ceramide and more complex sphingolipids constitute a diverse group of lipids that serve important roles as structural entities of biological membranes and as regulators of cellular growth, differentiation, and development. Thus, ceramides are vital players in numerous diseases including metabolic and cardiovascular diseases, as well as neurological disorders. Here we show that acyl-coenzyme A-binding protein (ACBP) potently facilitates very-long acyl chain ceramide synthesis. ACBP increases the activity of ceramide synthase 2 (CerS2) by more than 2-fold and CerS3 activity by 7-fold. ACBP binds very-long-chain acyl-CoA esters, which is required for its ability to stimulate CerS activity. We also show that high-speed liver cytosol from wild-type mice activates CerS3 activity, whereas cytosol from ACBP knock-out mice does not. Consistently, CerS2 and CerS3 activities are significantly reduced in the testes of ACBP mice, concomitant with a significant reduction in long- and very-long-chain ceramide levels. Importantly, we show that ACBP interacts with CerS2 and CerS3. Our data uncover a novel mode of regulation of very-long acyl chain ceramide synthesis by ACBP, which we anticipate is of crucial importance in understanding the regulation of ceramide metabolism in pathogenesis.
[Mh] Termos MeSH primário: Ceramidas/biossíntese
Inibidor da Ligação a Diazepam/metabolismo
Ácidos Graxos/metabolismo
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Ceramidas/genética
Inibidor da Ligação a Diazepam/genética
Ácidos Graxos/genética
Seres Humanos
Proteínas de Membrana/genética
Proteínas de Membrana/metabolismo
Camundongos
Camundongos Knockout
Esfingosina N-Aciltransferase/genética
Esfingosina N-Aciltransferase/metabolismo
Proteínas Supressoras de Tumor/genética
Proteínas Supressoras de Tumor/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ceramides); 0 (Diazepam Binding Inhibitor); 0 (Fatty Acids); 0 (Membrane Proteins); 0 (Tumor Suppressor Proteins); EC 2.3.1.24 (CERS2 protein, human); EC 2.3.1.24 (Cers2 protein, mouse); EC 2.3.1.24 (LASS3 protein, mouse); EC 2.3.1.24 (Sphingosine N-Acyltransferase); EC 2.3.1.24 (ceramide synthase 3, human)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170607
[Lr] Data última revisão:
170607
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170322
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.785345


  8 / 182 MEDLINE  
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[PMID]:28280117
[Au] Autor:Volpert G; Ben-Dor S; Tarcic O; Duan J; Saada A; Merrill AH; Pewzner-Jung Y; Futerman AH
[Ad] Endereço:Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel.
[Ti] Título:Oxidative stress elicited by modifying the ceramide acyl chain length reduces the rate of clathrin-mediated endocytosis.
[So] Source:J Cell Sci;130(8):1486-1493, 2017 Apr 15.
[Is] ISSN:1477-9137
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Sphingolipids modulate clathrin-mediated endocytosis (CME) by altering the biophysical properties of membranes. We now examine CME in astrocytes cultured from ceramide synthase 2 (CerS2) null mice, which have an altered sphingolipid acyl chain composition. The rate of endocytosis of low-density lipoprotein and transferrin, which are internalized via CME, was reduced in CerS2 null astrocytes, although the rate of caveolin-mediated endocytosis was unaltered. Levels of clathrin heavy chain were increased, which was due to decreased levels of Hsc70 (also known as HSPA8), a protein involved in clathrin uncoating. Hsc70 levels were decreased because of lower levels of binding of Sp1 to position -68 in the Hsc70 promoter. Levels of Sp1 were downregulated due to oxidative stress, which was elevated fourfold in CerS2 null astrocytes. Furthermore, induction of oxidative stress in wild-type astrocytes decreased the rate of CME, whereas amelioration of oxidative stress in CerS2 null astrocytes reversed the decrease. Our data are consistent with the notion that sphingolipids not only change membrane biophysical properties but also that changes in their composition can result in downstream effects that indirectly impinge upon a number of cellular pathways, such as CME.
[Mh] Termos MeSH primário: Astrócitos/fisiologia
Ceramidas/metabolismo
Endocitose
Fígado/fisiologia
Estresse Oxidativo/imunologia
Esfingolipídeos/metabolismo
Esfingosina N-Aciltransferase/metabolismo
[Mh] Termos MeSH secundário: Animais
Membrana Celular/metabolismo
Células Cultivadas
Ceramidas/química
Clatrina/metabolismo
Endocitose/genética
Camundongos
Camundongos Knockout
Estresse Oxidativo/genética
Engenharia de Proteínas
Transdução de Sinais
Esfingosina N-Aciltransferase/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ceramides); 0 (Clathrin); 0 (Sphingolipids); EC 2.3.1.24 (Cers2 protein, mouse); EC 2.3.1.24 (Sphingosine N-Acyltransferase)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170518
[Lr] Data última revisão:
170518
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170311
[St] Status:MEDLINE
[do] DOI:10.1242/jcs.199968


  9 / 182 MEDLINE  
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[PMID]:28198542
[Au] Autor:Rieck M; Kremser C; Jobin K; Mettke E; Kurts C; Gräler M; Willecke K; Kolanus W
[Ad] Endereço:Molecular Immunology and Cell Biology, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
[Ti] Título:Ceramide synthase 2 facilitates S1P-dependent egress of thymocytes into the circulation in mice.
[So] Source:Eur J Immunol;47(4):677-684, 2017 Apr.
[Is] ISSN:1521-4141
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Well-defined gradients of the lipid mediator sphingosine-1-phosphate (S1P) direct chemotactic egress of mature thymocytes from the thymus into the circulation. Although it is known that these gradients result from low S1P levels in the thymic parenchyma and high S1P concentrations at the exit sites and in the plasma, the biochemical mechanisms that regulate these differential S1P levels remain unclear. Several studies demonstrated that ceramide synthase 2 (Cers2) regulates the levels of the S1P precursor sphingosine. We, therefore, investigated whether Cers2 is involved in the regulation of S1P gradients and S1P-dependent egress into the circulation. By analyzing Cers2-deficient mice, we demonstrate that Cers2 limits the levels of S1P in thymus and blood to maintain functional S1P gradients that mediate thymocyte emigration into the circulation. This function is specific for Cers2, as we also show that Cers4 is not involved in the regulation of thymic egress. Our study identified Cers2 as an important regulator of S1P-dependent thymic egress, and thus contributes to the understanding of how S1P gradients are maintained in vivo.
[Mh] Termos MeSH primário: Quimiotaxia
Esfingosina N-Aciltransferase/metabolismo
Linfócitos T/fisiologia
Timócitos/fisiologia
Timo/imunologia
[Mh] Termos MeSH secundário: Animais
Diferenciação Celular
Movimento Celular
Células Cultivadas
Lisofosfolipídeos/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Esfingosina/análogos & derivados
Esfingosina/metabolismo
Esfingosina N-Aciltransferase/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Lysophospholipids); 26993-30-6 (sphingosine 1-phosphate); EC 2.3.1.24 (Cers2 protein, mouse); EC 2.3.1.24 (Sphingosine N-Acyltransferase); NGZ37HRE42 (Sphingosine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170216
[St] Status:MEDLINE
[do] DOI:10.1002/eji.201646623


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[PMID]:28035360
[Au] Autor:Kim MH; Ahn HK; Lee EJ; Kim SJ; Kim YR; Park JW; Park WJ
[Ad] Endereço:Department of Biochemistry, School of Medicine, Gachon University, Incheon 406­799, Republic of Korea.
[Ti] Título:Hepatic inflammatory cytokine production can be regulated by modulating sphingomyelinase and ceramide synthase 6.
[So] Source:Int J Mol Med;39(2):453-462, 2017 Feb.
[Is] ISSN:1791-244X
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:Chronic inflammation is associated with the pathogenesis of type 2 diabetes and diabetic complications, and palmitate has been nominated as a candidate for the molecular link between these disorders. Recently, a crucial role of ceramide in inflammation and metabolic diseases has been reported. Therefore, in this study, we investigated whether ceramide formation is involved in palmitate­induced hepatic inflammation in vitro and in vivo. Ceramide can be generated either by the de novo pathway or by sphingomyelin degradation, and six different ceramide synthases (CerS) determine the specific acyl chain length of ceramide in mammals. We examined the roles of CerS and sphingomyelinases (SMases) in the secretion of inflammatory cytokines, such as tumour necrosis factor (TNF)­α, interleukin (IL)­1ß, and IL­6 in Hep3B cells. Among the six CerS, CerS6 overexpression uniquely elevated TNF­α secretion via p38 mitogen­activated protein kinase (MAPK) activation. In addition, the treatment of CerS6 overexpressing cells with palmitate synergistically increased cytokine secretion. However, neither palmitate treatment nor CerS6 overexpression altered lipopolysaccharide (LPS)-induced cytokine secretion. Instead, the activation of acidic (A)­SMase was involved in LPS­induced cytokine secretion via the MAPK/NF­κB pathway. Finally, the suppression of ceramide generation via A­SMase inhibition or de novo ceramide synthesis decreased high­fat diet­induced hepatic cytokine production in vivo. On the whole, our results revealed that CerS6 played a role in TNF­α secretion, and palmitate augmented inflammatory responses in pathophysiological conditions in which CerS6 is overexpressed. In addition, A­SMase activation was shown to be involved in LPS­induced inflammatory processes, suggesting that the modulation of CerS6 and A­SMase may be a therapeutic target for controlling hepatic inflammation.
[Mh] Termos MeSH primário: Citocinas/metabolismo
Hepatócitos/metabolismo
Mediadores da Inflamação/metabolismo
Proteínas de Membrana/metabolismo
Esfingomielina Fosfodiesterase/metabolismo
Esfingosina N-Aciltransferase/metabolismo
[Mh] Termos MeSH secundário: Animais
Desipramina/administração & dosagem
Dieta Hiperlipídica
Ácidos Graxos Monoinsaturados/administração & dosagem
Masculino
Proteínas de Membrana/genética
Camundongos
NF-kappa B/metabolismo
Fosforilação
Transdução de Sinais
Esfingomielinas/metabolismo
Esfingosina N-Aciltransferase/genética
Fator de Necrose Tumoral alfa/metabolismo
Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytokines); 0 (Fatty Acids, Monounsaturated); 0 (Inflammation Mediators); 0 (Membrane Proteins); 0 (NF-kappa B); 0 (Sphingomyelins); 0 (Tumor Necrosis Factor-alpha); EC 2.3.1.24 (CERS6 protein, human); EC 2.3.1.24 (Sphingosine N-Acyltransferase); EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases); EC 3.1.4.12 (Sphingomyelin Phosphodiesterase); TG537D343B (Desipramine); YRM4E8R9ST (thermozymocidin)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170316
[Lr] Data última revisão:
170316
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161231
[St] Status:MEDLINE
[do] DOI:10.3892/ijmm.2016.2835



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