The equilibrium between long and very long chain ceramides is important for the fate of the cell and can be influenced by co-expression of CerS

Hartmann, Daniela; Wegner, Martin; Wanger, Ruth Anna; Ferreiròs, Nerea; Schreiber, Yannick; Lucks, Jessica; Schiffmann, Susanne; Geißlinger, Gerd; Grösch, Sabine

doi:10.1016/j.biocel.2013.03.012

Cited by 74 publications

(54 citation statements)

References 29 publications

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“…The formation of ceramide-enriched domains and platforms is largely dependent on the ceramide structure. Properties of ceramides with different fatty acyl chains have been examined in phosphatidylcholine model membranes (Pinto et al 2011), in animal models (Silva et al 2012) and in cultured cells in vitro (Hartmann et al 2013). It was determined that saturated ceramides and very long chain ceramides influence membrane biophysical properties which may compromise cellular processes such as trafficking, sorting and cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

“…It was determined that saturated ceramides and very long chain ceramides influence membrane biophysical properties which may compromise cellular processes such as trafficking, sorting and cell proliferation. The exposure of cell membranes to ceramide species with different acyl chain length and saturation might have a distinct biophysical impact on cell signaling and functionality (Pinto et al 2011; Grösch et al 2012; Silva et al 2012; Hartmann et al 2013; Park et al 2013). The function of the very long chain deoxy-ceramides is currently unknown.…”

Section: Discussionmentioning

confidence: 99%

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Increased Plasma Levels of Select Deoxy-ceramide and Ceramide Species are Associated with Increased Odds of Diabetic Neuropathy in Type 1 Diabetes: A Pilot Study

Hammad

Baker²,

Abiad

et al. 2016

Neuromol Med

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Plasma deoxy-sphingoid bases are elevated in type 2 diabetes patients and correlate with the stage of diabetic distal sensorimotor polyneuropathy; however, associations between deoxy-sphingolipids (DSL) and neuropathy in type 1 diabetes have not been examined. The primary aim of this exploratory pilot study was to assess the associations between multiple sphingolipid species including DSL and free amino acids and the presence of symptomatic neuropathy in a DCCT/EDIC type 1 diabetes subcohort. Using mass spectroscopy, plasma levels of DSL and free amino acids in DCCT/EDIC type 1 diabetes participants (n = 80), with and without symptoms of neuropathy, were investigated. Patient-determined neuropathy was based on 15-item self-administered questionnaire (Michigan Neuropathy Screening Instrument) developed to assess distal symmetrical peripheral neuropathy in diabetes. Patients who scored ≥4, or reported inability to sense their feet during walking or to distinguish hot from cold water while bathing were considered neuropathic. Plasma levels of ceramide, sphingomyelin, hexosyl- and lactosylceramide species, and amino acids were measured and analyzed relative to neuropathy status in the patient. Deoxy-C24-ceramide, C24- and C26-ceramide were higher in patients with neuropathy than those without neuropathy. Cysteine was higher in patients with neuropathy. No differences in other sphingolipids or amino acids were detected. The covariate-adjusted Odds Ratios of positive patient-reported neuropathy was associated with increased levels of deoxy-C24-, and deoxy-C24:1-ceramide; C22-, C24-, and C26-ceramide; and cysteine. Plasma deoxy-ceramide and ceramide species may have potential diagnostic and prognostic significance in diabetic neuropathy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Increased Plasma Levels of Select Deoxy-ceramide and Ceramide Species are Associated with Increased Odds of Diabetic Neuropathy in Type 1 Diabetes: A Pilot Study

Hammad

Baker²,

Abiad

et al. 2016

Neuromol Med

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“…The SL-acyl chain composition of the liver regulates insulin signaling by modifying insulin receptor translocation into membrane microdomains (35,135,139). Long-chain (C16 -C20) and very-long-chain (C22-C24) Cers exert opposing effects on cell proliferation, and also on plasma membrane fluidity (55-57, 69,70,73,74,147,151). Mice with deleted Cer synthase 2 (CerS2) preferentially synthesize very-longchain Cers (C22-C24) and exhibit a compensatory increase in C16 and sphinganine levels in the liver, which alters glucose metabolism, indicating the type of GSLs can determine the degree of insulin resistance (58, 137, 141).…”

Section: Sl Pathways In Diabetes Nafld and Nashmentioning

confidence: 99%

“…Activation of ASMase in steatohepatitis is induced by TNF-␣, reactive oxygen species, and oxidative stress (66,64,70). It is used in the regulation of steatosis, fibrosis, lipotoxicity, ER stress, autophagy, and lysosomal membrane permeabilization, contributing to ASH and NASH.…”

Section: Sl Pathways In Diabetes Nafld and Nashmentioning

confidence: 99%

“…ASMase deficiency interrupted the expression of ER stress markers after alcohol or HFD feeding (48,50,68). Although the chemotherapeutic agent cisplatin-activating ASMase leads to a exogenous delivery of D-e-C16-Cer, dihydro-C16-Cer does not result in changes in cell morphology and actin cytoskeleton in breast cancer (70,183,187). ASMase-induced Cer generation downregulates MAT1A mRNA expression, and decreases in MATI/III protein levels are induced by TNF-␣, resulting in SAM depletion and TNF-mediated liver failure (71,107,111).…”

Section: Sl Pathways In Diabetes Nafld and Nashmentioning

confidence: 99%

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Compounds of the sphingomyelin-ceramide-glycosphingolipid pathways as secondary messenger molecules: new targets for novel therapies for fatty liver disease and insulin resistance

Ilan

2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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The compounds of sphingomyelin-ceramide-glycosphingolipid pathways have been studied as potential secondary messenger molecules in various systems, along with liver function and insulin resistance. Secondary messenger molecules act directly or indirectly to affect cell organelles and intercellular interactions. Their potential role in the pathogenesis of steatohepatitis and diabetes has been suggested. Data samples collected from patients with Gaucher's disease, who had high levels of glucocerebroside, support a role for compounds from these pathways as a messenger molecules in the pathogenesis of fatty liver disease and diabetes. The present review summarizes some of the recent data on the role of glycosphingolipid molecules as messenger molecules in various physiological and pathological conditions, more specifically including insulin resistance and fatty liver disease.

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Variations in serum sphingolipid levels associate with liver fibrosis progression and poor treatment outcome in hepatitis C virus but not hepatitis B virus infection

et al. 2015

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Ablation of very-long-chain ceramides (Cers) with consecutive elevations in sphinganine levels has been shown to cause a severe hepatopathy in a knockout mouse model. We have recently shown that serum sphingolipids (SLs) are deregulated in patients with chronic liver disease. However, their role as possible biomarkers in liver fibrosis remains to date unexplored. We assessed, using liquid chromatography/tandem mass spectrometry, serum concentrations of various SL metabolites in 406 patients with chronic viral hepatitis, 203 infected with genotype 1 hepatitis C virus (HCV) and 203 with hepatitis B virus (HBV), respectively. We observed significant variations of serum SLs, with sphingosine and sphinganine being, both in univariate (P < 0.05) as well as in multivariate analysis, significantly associated to severity of liver fibrosis in HCV-infected patients (odds ratio [OR]: 1.111; confidence interval [CI]: 1.028-1.202; P 5 0.007 and OR, 0.634; CI, 0.435-0.925; P 5 0.018, respectively). Serum SLs correlated significantly with serum triglyceride and cholesterol levels as well as with insulin resistance, defined by the homeostatic model assessment index, in HCV patients. Sustained viral response rates in HCV patients were independently predicted by serum C24Cer (OR, 0.998; CI, 0.997-0.999; P 5 0.001), its unsaturated derivative C24:1Cer (OR, 1.001; CI, 1.000-1.002; P 5 0.059), and C18:1Cer (OR, 0.973; CI, 0.947-0.999; P 5 0.048), together with ferritin (OR, 1.006; CI, 1.003-1.010; P < 0.001), alkaline phosphatase (OR, 1.020; CI, 1.001-1.039; P 5 0.032), and interleukin-28B genotype (OR, 9.483; CI,; P < 0.001). Conclusion: Our study demonstrates a tight interaction between variations in serum SL levels and progression of liver fibrosis as well as responsiveness to antiviral therapy. Particularly, sphingosine, sphinganine, and C24Cer appear as promising novel biomarkers in chronic HCV infection and should be further evaluated within the noninvasive prediction of liver fibrosis. (HEPATOLOGY 2015;61:812-822)

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The equilibrium between long and very long chain ceramides is important for the fate of the cell and can be influenced by co-expression of CerS

Cited by 74 publications

References 29 publications

Increased Plasma Levels of Select Deoxy-ceramide and Ceramide Species are Associated with Increased Odds of Diabetic Neuropathy in Type 1 Diabetes: A Pilot Study

Increased Plasma Levels of Select Deoxy-ceramide and Ceramide Species are Associated with Increased Odds of Diabetic Neuropathy in Type 1 Diabetes: A Pilot Study

Compounds of the sphingomyelin-ceramide-glycosphingolipid pathways as secondary messenger molecules: new targets for novel therapies for fatty liver disease and insulin resistance

Variations in serum sphingolipid levels associate with liver fibrosis progression and poor treatment outcome in hepatitis C virus but not hepatitis B virus infection

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