• CerS2 levels are significantly elevated in breast cancer tissue compared to normal tissue, along with increased levels of ceramide synthase 6 (CerS6). (wikipedia.org)
  • Natural product anticancer agents enhance intracellular levels of ceramide, a sphingolipid that promotes cell apoptosis. (sphingolipidclub.com)
  • In the present study we examined the relationship between ceramide, ceramide metabolites and expression of the MDR1 gene in human breast cancer cell lines. (sphingolipidclub.com)
  • Four wild-type (drug-sensitive) human breast cancer cell lines (MCF-7, T47D,MDA-MB-231, MDA-MB-435) were used to evaluate the influence of acute and chronic exposure to ceramide and ceramide metabolites on MDR1 mRNA,P-gp, and resistance to chemotherapeutic agents. (sphingolipidclub.com)
  • These data are the first evidence that chronic exposure to ceramide and its metabolites enhances expression of the MDR phenotype in cancer cells. (sphingolipidclub.com)
  • The impact of sphingolipids on MDR1 gene expression in cancer appears to reflect the myriad intracellular signaling pathways of ceramide and its metabolites. (sphingolipidclub.com)
  • Notably, recent studies suggest that the accumulation of sphingolipids, namely ceramides and it's metabolites, play essential roles in the development of insulin resistance in tissues such as skeletal muscle, liver and, adipose tissue in obese rodents, and humans ( 6 - 20 ). (frontiersin.org)
  • In this review, we intend to provide a perspective on ceramides and ceramide metabolites in the maintenance of adipose tissue homeostasis and how adipose tissue ceramides contribute to the development of metabolic diseases. (frontiersin.org)
  • Sphingosine and its derivative sphinganine are the major bases of the sphingolipids in mammals. (foodb.ca)
  • Of the numerous lipid classes implicated in eliciting lipotoxicity, sphingolipid: ceramides are among the most deleterious as they modulate signaling pathways involved in regulating glucose metabolism, triglyceride synthesis, apoptosis, and fibrosis. (frontiersin.org)
  • 72 hours) to C8- ceramide (5 μg/ml culture medium), a cell-permeable analog of ceramide, enhanced MDR1 mRNA levels by 3- and 5-fold in T47D and inMDA-MB-435 cells, respectively, but did not affect MCF-7 cells.D-erythro-sphingosine exposure (5 μg/ml, 72 hr) increased MDR1 mRNA levels in MDA-MB-435 cells by 3.5-fold. (sphingolipidclub.com)
  • Ceramide synthase 2 is a ceramide synthase that catalyses the synthesis of very long acyl chain ceramides, including C20 and C26 ceramides. (wikipedia.org)
  • As it is apparent in this series, numerous studies have shown that manipulation of ceramide synthesis or degradation pathways in rodents through pharmacologic and genetic interventions have profound effects on insulin sensitivity ( 6 , 12 , 26 , 27 ). (frontiersin.org)
  • A critical role for ceramide synthase 2 in liver homeostasis: II. (wikipedia.org)
  • Ceramide synthase 2, also known as LAG1 longevity assurance homolog 2 or Tumor metastasis-suppressor gene 1 protein is an enzyme that in humans is encoded by the CERS2 gene. (wikipedia.org)
  • In humans, ceramides predict the occurrence of major adverse cardiac events, such that the numerous clinics have started to offer serum ceramide tests as prognostic measures of cardiovascular risk ( 24 , 25 ). (frontiersin.org)
  • These mice showed no decrease in overall ceramide level, but levels of sphinganine were elevated. (wikipedia.org)
  • In mice, blocking ceramide production improves insulin sensitivity, prevents β-cell failure, resolves hepatic steatosis, hypertriglyceridemia, and prevents atherosclerosis, and heart failure ( 6 - 22 ). (frontiersin.org)
  • CerS2 is much more widely distributed than Ceramide synthase 1 (CerS1) and is found in at least 12 tissues in the human body, with high expression in the kidney and liver, and moderate expression in the brain and other organs. (wikipedia.org)
  • 72 hours) of MDA-MB-231cells to C8-ceramide enhanced MDR1 mRNA levels by 45- and 370-fold(real-time RT-PCR) at passages 12 and 22, respectively, and elicited expression of P-gp (Western blot). (sphingolipidclub.com)
  • Exposure of cells to either octanoic acid (C8:0), a C8-ceramide hydrolysis product, or oleic acid (C18:1) did not affect MDR1 expression. (sphingolipidclub.com)
  • Simultaneously, the hormone regulates numerous metabolic enzymes (e.g., glycogen synthase or pp70 S6-kinase) to promote storage of the incoming glucose as glycogen, triglyceride, or protein. (medscape.com)
  • 7. Activity of glycogen synthase kinase-3beta is down-regulated during transient differentiation of human colon cancer HT-29 cells. (nih.gov)
  • 12. Glycogen synthase kinase-3 is a negative regulator of extracellular signal-regulated kinase. (nih.gov)
  • 13. Interaction of human biliverdin reductase with Akt/protein kinase B and phosphatidylinositol-dependent kinase 1 regulates glycogen synthase kinase 3 activity: a novel mechanism of Akt activation. (nih.gov)
  • 15. Dysregulation of glycogen synthase kinase-3beta signaling in hepatocellular carcinoma cells. (nih.gov)
  • 20. Genetic deletion of glycogen synthase kinase-3beta abrogates activation of IkappaBalpha kinase, JNK, Akt, and p44/p42 MAPK but potentiates apoptosis induced by tumor necrosis factor. (nih.gov)
  • Dihydrosphingosine is acylated by one of six (dihydro)-ceramide synthase, CerS - originally termed LASS - to form dihydroceramide. (cloudfront.net)
  • Specifically, in 1996, two independent laboratories found that treating cultured cells with short-chain ceramide analogs or bacterial sphingomyelinases, which hydrolyze sphingomyelin to form choline and ceramide (Figure 1), blocked insulin-stimulated tyrosine phosphorylation of IRS-1 and its subsequent recruitment and activation of PI3K. (medscape.com)
  • Sphingomyelin synthase 2 (SMS2) is a Golgi-localized enzyme that synthesizes sphingomyelin, a critical lipid in the plasma membrane, and mutations in SMS2 underly a rare genetic disorder of bone formation. (sciety.org)
  • We previously identified mutations in sphingomyelin synthase SMS2 that cause osteoporosis and skeletal dysplasia. (sciety.org)
  • In animals large amounts of So and Sa are produced in liver, kidney, and other tissues following FB inhibition of ceramide synthase (CerS). (theupperroomsite.com)
  • De novo generated ceramide is the central hub of the sphingolipid network and subsequently has several fates. (cloudfront.net)
  • Ceramide is produced in mammalian systems by desaturation of dihydroceramide by dihydroceramide desaturase 1 (DES1). (cloudfront.net)
  • Schematic diagram depicting the pathways linking ceramides to the inhibition of IRS-1 and Akt/PKB. (medscape.com)
  • As described in the text, ceramides have been shown to independently promote the serine/threonine phosphorylation and inhibition of IRS-1, block the translocation of Akt/PKB to the plasma membrane, and catalyze the dephosphorylation of Akt/PKB by protein phosphatase 2A. (medscape.com)
  • 9. Sphinganine causes early activation of JNK and p38 MAPK and inhibition of AKT activation in HT-29 human colon cancer cells. (nih.gov)
  • 10. Ceramide 1-phosphate stimulates macrophage proliferation through activation of the PI3-kinase/PKB, JNK and ERK1/2 pathways. (nih.gov)
  • It may be phosphorylated by ceramide kinase to form ceramide-1-phosphate. (cloudfront.net)
  • These compounds, specifically known as phytosphingosine and dihydrosphingosine (also known as sphinganine, [2] although this term is less common), are mainly C 18 compounds, with somewhat lower levels of C 20 bases. (cloudfront.net)
  • CerS2 is much more widely distributed than Ceramide synthase 1 (CerS1) and is found in at least 12 tissues in the human body, with high expression in the kidney and liver, and moderate expression in the brain and other organs. (wikipedia.org)
  • A critical role for ceramide synthase 2 in liver homeostasis: II. (wikipedia.org)
  • These mice showed no decrease in overall ceramide level, but levels of sphinganine were elevated. (wikipedia.org)
  • CerS2 levels are significantly elevated in breast cancer tissue compared to normal tissue, along with increased levels of ceramide synthase 6 (CerS6). (wikipedia.org)
  • [ 28 ] described a negative correlation between ceramide content of muscles and insulin sensitivity in 13 human subjects and further demonstrated that lipid infusion markedly elevated ceramide levels while decreasing insulin sensitivity. (medscape.com)
  • Exercise training, which improves insulin sensitivity, markedly decreases muscle ceramide levels in both rats and humans. (medscape.com)
  • To evaluate the role of ceramides in the insulin resistance associated with lipid oversupply, scientists have investigated the lipid's role in FFA-induced insulin resistance using cultured myotubes. (medscape.com)
  • The downward arrow following to ceramide shows the reduction in ceramide biosynthesis in cells. (theupperroomsite.com)
  • [ 58 ] However, the effect of ceramide on IRS and/or PI3K appears to be specific to certain cells or treatment conditions, as a number of different laboratories have shown that ceramide has no effect on PI3K or the production of its lipid products. (medscape.com)
  • This highly bioactive molecule may also be phosphorylated to form ceramide-1-phosphate. (cloudfront.net)
  • Dihydroceramides are then desaturated to form ceramide. (cloudfront.net)
  • Sphingomyelins have a phosphocholine or phosphoethanolamine molecule with an ester linkage to the 1-hydroxy group of a ceramide. (cloudfront.net)