المؤلفون: Paul J. Nietert, Waleed O. Twal, Jim C. Oates, Olivia C Harden, Dulaney A. Wilson, Samar M. Hammad

المصدر: Frontiers in Immunology
Frontiers in Immunology, Vol 12 (2021)

مصطلحات موضوعية: 0301 basic medicine, Carotid Artery Diseases, Male, Time Factors, Disease, 030204 cardiovascular system & hematology, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Immunology and Allergy, Lupus Erythematosus, Systemic, Prospective Studies, skin and connective tissue diseases, Original Research, Ultrasonography, music.instrument, Systemic lupus erythematosus, sphingosine, Middle Aged, Prognosis, Plaque, Atherosclerotic, Race Factors, Female, Sphingomyelin, Adult, medicine.medical_specialty, Immunology, sphingomyelin, LDL, 03 medical and health sciences, Lactosylceramide, Predictive Value of Tests, Internal medicine, medicine, Humans, ceramide, music, Autoimmune disease, Sphingolipids, Sphingosine, business.industry, lupus, RC581-607, medicine.disease, Sphingolipid, lactosylceramide, Black or African American, 030104 developmental biology, Cross-Sectional Studies, chemistry, Subclinical atherosclerosis, Asymptomatic Diseases, Lipidomics, sphingolipid, Immunologic diseases. Allergy, atherosclerosis, business, Biomarkers

الوصف: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects females more than males, with African Americans developing more severe manifestation of the disease. SLE patients are at increased risk for cardiovascular disease (CVD), and SLE women 35-44 years old have 50 fold the incidence rate of CVD. Because SLE patients do not follow the typical age and gender pattern for CVD, but instead an accelerated disease course, the traditional biomarkers of elevated LDL and total cholesterol levels do not accurately assess their CVD risk. Recently, we have reported that African American SLE patients had higher ceramide, hexosylceramide, sphingosine and dihydrosphingosine 1-phosphate levels compared to their healthy controls, and those with atherosclerosis had higher sphingomyelin and sphingoid bases levels than those without (PLoS One. 2019; e0224496). In the current study, we sought to identify sphingolipid species that correlate with and pose the potential to predict atherosclerosis severity in African American SLE patients. Plasma samples from a group of African American predominantly female SLE patients with well-defined carotid atherosclerotic plaque burden were analyzed for sphingolipidomics using targeted mass spectroscopy. The data demonstrated that at baseline, plaque area and C3 values correlated inversely with most lactoceramide species. After one-year follow-up visit, values of the change of plaque area correlated positively with the lactoceramide species. There was no correlation between LDL-C concentrations and lactoceramide species. Taken together, lactocylcermide levels may have a ‘predictive’ value and sphingolipidomics have an added benefit to currently available tools in early diagnosis and prognosis of African American SLE patients with CVD.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ef92dc11ae73bc555cfdaade7fec62e7Test
http://europepmc.org/articles/PMC8335560Test

المؤلفون: Samar M. Hammad, Marina Cuchel, Daniel J. Rader, Meghan T. Walsh, M. Mahmood Hussain, Jahangir Iqbal

المصدر: Journal of Lipid Research, Vol 59, Iss 11, Pp 2084-2097 (2018)

مصطلحات موضوعية: 0301 basic medicine, ATP-binding cassette family, Male, medicine.medical_specialty, Ceramide, Blotting, Western, microsomal triglyceride transfer protein, QD415-436, Biochemistry, Microsomal triglyceride transfer protein, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Endocrinology, Tangier disease, Internal medicine, Cell Line, Tumor, medicine, Animals, Humans, Research Articles, sphingolipids, ceramides, biology, Chemistry, A protein, Cell Biology, medicine.disease, Sphingolipid, Sphingomyelins, Mice, Inbred C57BL, lipoproteins, 030104 developmental biology, Apolipoproteins, Liver, ABCA1, biology.protein, lipids (amino acids, peptides, and proteins), Sphingomyelin, 030217 neurology & neurosurgery, ATP Binding Cassette Transporter 1

الوصف: Sphingolipids, including ceramide, SM, and hexosylceramide (HxCer), are carried in the plasma by lipoproteins. They are possible markers of metabolic diseases, but little is known about their control. We previously showed that microsomal triglyceride transfer protein (MTP) is critical to determine plasma ceramide and SM, but not HxCer, levels. In human plasma and mouse models, we examined possible HxCer-modulating pathways, including the role of ABCA1 in determining sphingolipid plasma concentrations. Compared with control samples, plasma from patients with Tangier disease (deficient in ABCA1) had significantly lower HxCer (-69%) and SM (-40%) levels. Similarly, mice deficient in hepatic and intestinal ABCA1 had significantly reduced HxCer (-79%) and SM (-85%) levels. Tissue-specific ablation studies revealed that hepatic ABCA1 determines plasma HxCer and SM levels; that ablation of MTP and ABCA1 in the liver and intestine reduces plasma HxCer, SM, and ceramide levels; and that hepatic and intestinal MTP contribute to plasma ceramide levels, whereas only hepatic MTP modulates plasma SM levels. These results identify the contribution of ABCA1 to plasma SM and HxCer levels and suggest that MTP and ABCA1 are critical determinants of plasma sphingolipid levels.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6874bd7437fa33cce8da210d568e81ceTest
http://www.sciencedirect.com/science/article/pii/S0022227520309093Test

المؤلفون: Waleed O. Twal, Deepak Nihalani, Samar M. Hammad, Ehtesham Arif, Andrea J. Semler, Richard L. Klein

المصدر: Genes
Volume 11
Issue 2
Genes, Vol 11, Iss 2, p 178 (2020)

مصطلحات موضوعية: 0301 basic medicine, Ceramide, podocyte, lcsh:QH426-470, Lipoproteins, Apoptosis, Ceramides, Article, Cell Line, Podocyte, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Downregulation and upregulation, Genetics, medicine, Humans, 030212 general & internal medicine, RNA-Seq, ceramide, Phosphorylation, Genetics (clinical), PI3K/AKT/mTOR pathway, Carbon Isotopes, Focal Adhesions, sphingolipids, Podocytes, Chemistry, TOR Serine-Threonine Kinases, Cholesterol, HDL, lipoprotein, Lipid Metabolism, Sphingolipid, Cell biology, lcsh:Genetics, 030104 developmental biology, medicine.anatomical_structure, mTOR, lipids (amino acids, peptides, and proteins), Signal transduction, Transcriptome, Signal Transduction, Lipoprotein

الوصف: Sphingolipids are bioactive lipids associated with cellular membranes and plasma lipoproteins, and their synthesis and degradation are tightly regulated. We have previously determined that low plasma concentrations of certain ceramide species predict the development of nephropathy in diabetes patients with normal albumin excretion rates at baseline. Herein, we tested the hypothesis that altering the sphingolipid content of circulating lipoproteins can alter the metabolic and signaling pathways in podocytes, whose dysfunction leads to an impairment of glomerular filtration. Cultured human podocytes were treated with lipoproteins from healthy subjects enriched in vitro with C16 ceramide, or D-erythro 2-hydroxy C16 ceramide, a ceramide naturally found in skin. The RNA-Seq data demonstrated differential expression of genes regulating sphingolipid metabolism, sphingolipid signaling, and mTOR signaling pathways. A multiplex analysis of mTOR signaling pathway intermediates showed that the majority (eight) of the pathway phosphorylated proteins measured (eleven) were significantly downregulated in response to C16 ceramide-enriched HDL2 compared to HDL2 alone and hydroxy ceramide-enriched HDL2. In contrast, C16 ceramide-enriched HDL3 upregulated the phosphorylation of four intermediates in the mTOR pathway. These findings highlight a possible role for lipoprotein-associated sphingolipids in regulating metabolic and signaling pathways in podocytes and could lead to novel therapeutic targets in glomerular kidney diseases.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ace67530355a42fb9c710a2be9460940Test

المؤلفون: Jahangir Iqbal, Meghan T. Walsh, Samar M. Hammad, M. Mahmood Hussain

المصدر: Trends in Endocrinology & Metabolism. 28:506-518

مصطلحات موضوعية: 0301 basic medicine, Ceramide, Extracellular transport, Lipoproteins, Endocrinology, Diabetes and Metabolism, 030204 cardiovascular system & hematology, Biology, Bioinformatics, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Insulin resistance, Metabolic Diseases, Diabetes mellitus, Nonalcoholic fatty liver disease, medicine, Animals, Humans, Secretion, Sphingolipids, medicine.disease, Sphingolipid, 030104 developmental biology, chemistry, Biochemistry, Health, lipids (amino acids, peptides, and proteins), Insulin Resistance, Sphingomyelin

الوصف: Sphingolipids are structurally and functionally diverse molecules with significant physiologic functions and are found associated with cellular membranes and plasma lipoproteins. The cellular and plasma concentrations of sphingolipids are altered in several metabolic disorders and may serve as prognostic and diagnostic markers. Here we discuss various sphingolipid transport mechanisms and highlight how changes in cellular and plasma sphingolipid levels contribute to cardiovascular disease, obesity, diabetes, insulin resistance, and nonalcoholic fatty liver disease (NAFLD). Understanding of the mechanisms involved in intracellular transport, secretion, and extracellular transport may provide novel information that might be amenable to therapeutic targeting for the treatment of various metabolic disorders.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::02609a6d0d9f3afc17a5c0e0f55e6eb2Test
https://doi.org/10.1016/j.tem.2017.03.005Test

المؤلفون: Stefanka D. Spassieva, Jad M. El Abiad, Samar M. Hammad, Dcct, Nathaniel L. Baker, Richard L. Klein, Maria F. Lopes-Virella, Barbara Rembiesa, Jacek Bielawski, Jason S. Pierce

المصدر: NeuroMolecular Medicine. 19:46-56

مصطلحات موضوعية: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Ceramide, Diabetic neuropathy, Pilot Projects, 030209 endocrinology & metabolism, Type 2 diabetes, Ceramides, Article, Glycosphingolipids, Young Adult, 03 medical and health sciences, Cellular and Molecular Neuroscience, Lactosylceramide, chemistry.chemical_compound, 0302 clinical medicine, Diabetic Neuropathies, Tandem Mass Spectrometry, Internal medicine, Diabetes mellitus, Odds Ratio, Humans, Medicine, Cysteine, Amino Acids, music, Sphingolipids, Type 1 diabetes, music.instrument, business.industry, medicine.disease, Sphingolipid, Sphingomyelins, Observational Studies as Topic, Cross-Sectional Studies, Diabetes Mellitus, Type 1, 030104 developmental biology, Peripheral neuropathy, Endocrinology, Neurology, chemistry, Sensation Disorders, Molecular Medicine, Female, business, Follow-Up Studies

الوصف: 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.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::acd42c7d2511b600436ec7f3cd0b0418Test
https://doi.org/10.1007/s12017-016-8423-9Test

المؤلفون: Waleed O. Twal, Paul J. Nietert, Jim C. Oates, Jasmyn R. Hardin, Samar M. Hammad, Dulaney A. Wilson

المصدر: PLoS ONE
PLoS ONE, Vol 14, Iss 11, p e0224496 (2019)

مصطلحات موضوعية: 0301 basic medicine, Physiology, Comorbidity, Cardiovascular Medicine, Biochemistry, Vascular Medicine, Mass Spectrometry, chemistry.chemical_compound, 0302 clinical medicine, immune system diseases, Medicine and Health Sciences, Ethnicities, Lupus Erythematosus, Systemic, African American people, skin and connective tissue diseases, Multidisciplinary, Systemic lupus erythematosus, Population groupings, Middle Aged, Lipids, Body Fluids, 3. Good health, Chemistry, Blood, Cholesterol, Cardiovascular Diseases, 030220 oncology & carcinogenesis, Physical Sciences, Medicine, Female, Anatomy, Sphingomyelin, Research Article, Adult, Ceramide, Science, Immunology, Systemic Lupus Erythematosus, Blood Plasma, White People, Autoimmune Diseases, Phosphates, Young Adult, 03 medical and health sciences, Rheumatology, medicine, Humans, Autoimmune disease, Sphingolipids, Lupus erythematosus, Lupus Erythematosus, Sphingosine, business.industry, Chemical Compounds, Case-control study, Biology and Life Sciences, Health Status Disparities, Atherosclerosis, medicine.disease, Sphingolipid, Black or African American, 030104 developmental biology, chemistry, Case-Control Studies, Lipidomics, Clinical Immunology, Clinical Medicine, People and places, business

الوصف: Systemic lupus erythematous (SLE) is a chronic multi-organ autoimmune disease. Genetic and environmental factors contribute to disease onset and severity. Sphingolipids are signaling molecules involved in regulating cell functions and have been associated with multiple genetic disease processes. African-Americans are more likely to suffer from SLE morbidity than Whites. The Medical University of South Carolina has banked plasma samples from a well-characterized lupus cohort that includes African-Americans and Whites. This study examined the influence of race on plasma sphingolipid profiles in SLE patients and association of sphingolipid levels with comorbid atherosclerosis and SLE disease activity. Mass spectrometry revealed that healthy African-Americans had higher sphingomyelin levels and lower lactosylcermide levels compared to healthy Whites. SLE patients, irrespective of race, had higher levels of ceramides, and sphingoid bases (sphingosine and dihydrosphingosine) and their phosphates compared to healthy subjects. Compared to African-American controls, African-American SLE patients had higher levels of ceramides, hexosylceramides, sphingosine and dihydrosphingosine 1-phosphate. Compared to White controls, White SLE patients exhibited higher levels of sphingoid bases and their phosphates, but lower ratios of C16:0 ceramide/sphingosine 1-phosphate and C24:1 ceramide/sphingosine 1-phosphate. White SLE patients with atherosclerosis exhibited lower levels of sphingoid bases compared to White SLE patients without atherosclerosis. In contrast, African-American SLE patients with atherosclerosis had higher levels of sphingoid bases and sphingomyelins compared to African-American SLE patients without atherosclerosis. Compared to White SLE patients with atherosclerosis, African-American SLE patients with atherosclerosis had higher levels of select sphingolipids. Plasma levels of sphingosine, C16:0 ceramide/sphingosine 1-phosphate ratio and C24:1 ceramide/sphingosine 1-phosphate ratio significantly correlated with SLEDAI in the African-American but not White SLE patients. The C16:0 ceramide/sphingosine 1-phosphate ratio in SLE patients, and levels of C18:1 and C26:1 lactosylcermides, C20:0 hexosylceramide, and sphingoid bases in SLE patients with atherosclerosis could be dependent on race. Further ethnic studies in SLE cohorts are necessary to verify use of sphingolipidomics as complementary diagnostic tool.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::188b8bfbb83f031308b820bfd5c07ed7Test
https://doi.org/10.1371/journal.pone.0224496Test

المؤلفون: Gayenell S. Magwood, Paul J. Nietert, Robert J. Adams, Samar M. Hammad, Joy N. Jones Buie, Leonardo Bonilha, Catrina Sims-Robinson

المصدر: PLoS ONE
PLoS ONE, Vol 14, Iss 5, p e0216213 (2019)

مصطلحات موضوعية: Male, 0301 basic medicine, Physiology, Cross-sectional study, Blood Pressure, Cardiovascular Medicine, 030204 cardiovascular system & hematology, Biochemistry, Vascular Medicine, chemistry.chemical_compound, Endocrinology, 0302 clinical medicine, Risk Factors, Sphingosine, Medicine and Health Sciences, Ethnicities, African American people, Chromatography, High Pressure Liquid, Multidisciplinary, Middle Aged, Population groupings, Lipids, Body Fluids, 3. Good health, Blood, Cardiovascular Diseases, Hypertension, Cohort, Medicine, Female, Anatomy, Research Article, Adult, medicine.medical_specialty, Ceramide, Endocrine Disorders, Science, Hypercholesterolemia, Ceramides, Gas Chromatography-Mass Spectrometry, White People, Blood Plasma, 03 medical and health sciences, Insulin resistance, Internal medicine, Diabetes mellitus, Diabetes Mellitus, medicine, Humans, Aged, Dyslipidemias, Sphingolipids, Endocrine Physiology, business.industry, Biology and Life Sciences, medicine.disease, Obesity, Sphingolipid, Black or African American, Cross-Sectional Studies, 030104 developmental biology, chemistry, Metabolic Disorders, Lysophospholipids, People and places, Insulin Resistance, business, Dyslipidemia

الوصف: BackgroundPopulation-wide reductions in cardiovascular disease (CVD) have not been equally shared in the African American community due to a higher burden of CVD risk factors such as metabolic disorders and obesity. Differential concentrations of sphingolipids such as ceramide, sphingosine, and sphingosine 1-phosphate (S1P) has been associated with the development of CVD, metabolic disorders (MetD), and obesity. Whether African Americans have disparate expression levels of sphingolipids that explain higher burdens of CVD remains unknown.MethodsA cross sectional analysis of plasma concentrations of ceramides, sphingosine, and S1P were measured from 8 whites and 7 African Americans without metabolic disorders and 7 whites and 8 African Americans with metabolic disorders using high performance liquid chromatography/tandem mass spectrometry methodology (HPLC/MS-MS). Subjects were stratified by both race and metabolic status. Subjects with one or more of the following physician confirmed diagnosis: diabetes, hypertension, hypercholesterolemia, or dyslipidemia were classified as having metabolic disease (MetD). Data was analyzed using a Two-Way ANOVA and Tukey's post hoc test.ResultsTotal ceramide levels were increased in African Americans compared to African Americans with MetD. Ceramide C16 levels were higher in whites with MetD compared to African Americans with MetD (pConclusionsPlasma ceramide concentration patterns are distinct in African Americans with MetD. Further research with larger samples sizes are needed to confirm these findings and to understand whether racial disparities in sphingolipid concentrations have potential therapeutic implications for CVD-related health outcomes.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::abb7e2b274d30614592aacf90be11f70Test
https://doi.org/10.1371/journal.pone.0216213Test

المؤلفون: Nalini Mayroo, Samar M. Hammad, Alicja Bielawska, Kent J. Smith, Gabriel Virella, Mohammed M. Al Gadban, Yusuf A. Hannun, Jean-Philip Truman, Maria F. Lopes-Virella, Russell W. Jenkins

المصدر: Immunology. 136:30-45

مصطلحات موضوعية: Ceramide, Phagocytosis, Monocyte, medicine.medical_treatment, Immunology, Biology, Cell biology, chemistry.chemical_compound, medicine.anatomical_structure, Cytokine, Biochemistry, chemistry, Lysosome, medicine, Immunology and Allergy, lipids (amino acids, peptides, and proteins), Scavenger receptor, Acid sphingomyelinase, Sphingomyelin, medicine.drug

الوصف: Oxidized low-density lipoprotein (oxLDL) and oxLDL-containing immune complexes (oxLDL-IC) contribute to the formation of lipid-laden macrophages (foam cells). Fcγ receptors mediate uptake of oxLDL-IC, whereas scavenger receptors internalize oxLDL. We have previously reported that oxLDL-IC, but not free oxLDL, activate macrophages and prolong their survival. Sphingomyelin is a major constituent of cell membranes and lipoprotein particles and acid sphingomyelinase (ASMase) hydrolyses sphingomyelin to generate the bioactive lipid ceramide. ASMase exists in two forms: lysosomal (L-ASMase) and secretory (S-ASMase). In this study we examined whether oxLDL and oxLDL-IC regulate ASMase differently, and whether ASMase mediates monocyte/macrophage activation and cytokine release. The oxLDL-IC, but not oxLDL, induced early and consistent release of catalytically active S-ASMase. The oxLDL-IC also consistently stimulated L-ASMase activity, whereas oxLDL induced a rapid transient increase in L-ASMase activity before it steadily declined below baseline. Prolonged exposure to oxLDL increased L-ASMase activity; however, activity remained significantly lower than that induced by oxLDL-IC. Further studies were aimed at defining the function of the activated ASMase. In response to oxLDL-IC, heat-shock protein 70B' (HSP70B') was up-regulated and localized with redistributed ASMase in the endosomal compartment outside the lysosome. Treatment with oxLDL-IC induced the formation and release of HSP70-containing and IL-1β-containing exosomes via an ASMase-dependent mechanism. Taken together, the results suggest that oxLDL and oxLDL-IC differentially regulate ASMase activity, and the pro-inflammatory responses to oxLDL-IC are mediated by prolonged activation of ASMase. These findings may contribute to increased understanding of mechanisms mediating macrophage involvement in atherosclerosis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::91c1481163b1a1f2a43519ed662b5dcdTest
https://doi.org/10.1111/j.1365-2567.2012.03552.xTest

المؤلفون: Mohammed M. Al Gadban, Jean-Philip Truman, Kent J. Smith, Samar M. Hammad

المصدر: Cellular and Molecular Life Sciences. 68:3293-3305

مصطلحات موضوعية: Ceramide, Biology, Sphingomyelin phosphodiesterase, Article, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Lysosome, medicine, Animals, Humans, Macrophage, Molecular Biology, Tissue homeostasis, Pharmacology, Innate immune system, Macrophages, Cell Biology, Cell biology, Sphingomyelin Phosphodiesterase, medicine.anatomical_structure, Biochemistry, chemistry, Molecular Medicine, Acid sphingomyelinase, Sphingomyelin, medicine.drug

الوصف: Macrophages play a central role in innate immune responses, in disposal of cholesterol, and in tissue homeostasis and remodeling. To perform these vital functions macrophages display high endosomal/lysosomal activities. Recent studies have highlighted that acid sphingomyelinase (ASMase), which generates ceramide from sphingomyelin, is involved in modulation of membrane structures and signal transduction in addition to its metabolic role in the lysosome. In this review, we bring together studies on ASMase, its different forms and locations that are necessary for the macrophage to accomplish its diverse functions. We also address the importance of ASMase to several disease processes that are mediated by activated macrophages.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d049a3350554cb3b4f789e7514c28c8cTest
https://doi.org/10.1007/s00018-011-0686-6Test

المؤلفون: Barbara Rembiesa, Samar M. Hammad, Jacek Bielawski, Kent J. Smith, Alicja Bielawska, Yusuf A. Hannun, Jason S. Pierce, Farzan Soodavar, Richard L. Klein, Mohammed M. Al Gadban

المصدر: Journal of Lipid Research, Vol 51, Iss 10, Pp 3074-3087 (2010)

مصطلحات موضوعية: Adult, Male, Proteomics, medicine.medical_specialty, Ceramide, Very low-density lipoprotein, QD415-436, Biology, Ceramides, Biochemistry, sphingomyelin, chemistry.chemical_compound, Lactosylceramide, Endocrinology, Tandem Mass Spectrometry, Internal medicine, medicine, Methods, Humans, ceramide, music, Chromatography, High Pressure Liquid, Sphingolipids, music.instrument, Sphingosine, sphingosine, Heparin, Cell Biology, Sphingolipid, Sphingomyelins, carbohydrates (lipids), sphingolipid metabolome, chemistry, Female, lipids (amino acids, peptides, and proteins), Sample collection, Sphingomyelin, Lipoprotein

الوصف: We used a HPLC-MS/MS methodology for determination of a basic metabolomic profile (18:1,18:0 sphingoid backbone, C(14)-C(26) N-acyl part) of "normal" sphingolipid levels in human serum and plasma. Blood was collected from healthy males and nonpregnant females under fasting and nonfasting conditions with and without anticoagulants. Sphingolipids analyzed included sphingoid bases, sphingosine and dihydrosphingosine, their 1-phosphates (S1P and dhS1P), molecular species (C(n)-) of ceramide (Cer), sphingomyelin (SM), hexosylceramide (HexCer), lactosylceramide (LacCer), and Cer 1-phosphate (Cer1P). SM, LacCer, HexCer, Cer, and Cer1P constituted 87.7, 5.8, 3.4, 2.8, and 0.15% of total sphingolipids, respectively. The abundant circulating SM was C(16)-SM (64.0 µM), and it increased with fasting (100 µM). The abundant LacCer was C(16)-LacCer (10.0 µM) and the abundant HexCer was C(24)-HexCer (2.5 µM). The abundant Cer, C(24)-Cer (4.0 µM), was not influenced by fasting; however, levels of C(16)-C(20) Cers were decreased in response to fasting. S1P levels were higher in serum than plasma (0.68 µM vs. 0.32 µM). We also determined levels of sphingoid bases and SM species in isolated lipoprotein classes. HDL(3) was the major carrier of S1P, dhS1P, and Sph, and LDL was the major carrier of Cer and dhSph. Per particle, VLDL contained the highest levels of SM, Cer, and S1P. HPLC-MS/MS should provide a tool for clinical testing of circulating bioactive sphingolipids in human blood.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::76b3f2a09c7dd93ac3e2b4845a16989fTest
http://www.sciencedirect.com/science/article/pii/S0022227520409976Test