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Jie Xu - One of the best experts on this subject based on the ideXlab platform.

  • Effects of dietary Glucocerebrosides from sea cucumber on the brain sphingolipid profiles of mouse models of Alzheimer's disease
    Food & Function, 2017
    Co-Authors: Yu Song, Yu Ming Wang, Pei Xu Cong, Ling Lu, Qingjuan Tang, Hongwei Zhang, Jie Xu
    Abstract:

    Herein, we investigated the potential relationship between sphingolipids and Alzheimer's disease (AD) with special attention to the relationship between dietary sea cucumber Glucocerebrosides (SCGs) and sphingolipid metabolism. We assessed animal behavior using the Morris water maze test, determined Aβ1-42 concentration in the hippocampus using ELISA, and assessed the sphingolipid profile of the hippocampus and the cortex in normal mice (SAMR1), AD mice (SAMP8), and AD mice (SAMP8) fed with SCG using liquid chromatography-triple quadrupole mass spectrometry. We found that the SAMP8 mice had impaired memory and an SCG diet significantly rescued spatial memory deficits in these mice. As expected, we found that the profiles of sphingolipid species and the levels of total cerebrosides (CBS), ceramides (Cer), and sulfatides (ST) were significantly different in both the hippocampus and the cortex between the three groups; moreover, there were significantly lower ST levels and higher Cer and CBS levels in these regions in the SAMP8 mice. In the AD-SCG group, Cer and ST levels were altered only in the hippocampus, in contrast to the AD group. The major molecular species ST (d18:1-C24:1) and Cer (d18:1/18:0) were especially different between those of the two groups. Unexpectedly, sphingolipid profiles, including the nonhydroxylated fatty acid-ST/hydroxylated fatty acid-ST, very long fatty acid-galactocerebroside/long fatty acid-galactocerebroside, nonhydroxylated fatty acid-galactocerebroside/hydroxylated fatty acid-galactocerebroside and galactocerebroside/Glucocerebroside ratios, were affected by AD. Thus, the ST and Cer levels and the profiles of sphingolipid species in the AD-SCG group were significantly different compared to those of the AD model group. Therefore, SCG has potential ameliorative effects in AD, and exogenous sphingolipid intake may potentially influence sphingolipid metabolism in vivo.

  • Structure of Sphingolipids From Sea Cucumber Cucumaria frondosa and Structure-Specific Cytotoxicity Against Human HepG2 Cells
    Lipids, 2016
    Co-Authors: Yu Song, Pei Xu Cong, Xiaoxu Wang, Jie Xu
    Abstract:

    To investigate the relationship between structure and activity, three Glucocerebroside series (CFC-1, CFC-2 and CFC-3), ceramides (CF-Cer) and long-chain bases (CF-LCB) of sea cucumber Cucumaria frondosa (C. frondosa) were isolated and evaluated in HepG2 cells. The molecular species of CFC-1, CFC-2 and CFC-3 and CF-Cer were identified using reversed-phase liquid chromatography with heated electrospray ionization coupled to high-resolution mass spectrometry (RPLC-HESI-HRMS), and determined on the basis of chemical and spectroscopic evidence: For the three Glucocerebroside series, fatty acids (FA) were mainly saturated (18:0 and 22:0), monounsaturated (22:1, 23:1 and 24:1) and 2-hydroxyl FA (2-HFA) (23:1 h and 24:1 h), the structure of long-chain bases (LCB) were dihydroxy (d17:1, d18:1 and d18:2) and trihydroxy (t16:0 and t17:0), and the glycosylation was glucose; For CF-Cer, FA were primarily saturated (17:0) and monounsaturated (16:1 and 19:1), the structure of LCB were dihydroxy (d17:1 and d18:1), and trihydroxy (t16:0). The results of cell experiment indicated that all of three Glucocerebroside series, CF-Cer and CF-LCB exhibited an inhibitory effects on cell proliferation. Moreover, CFC-3 was most effective in three Glucocerebrosides to HepG-2 cell viability. The inhibition effect of CF-LCB was the strongest, and the inhibition effect of CF-Cer was much stronger than Glucocerebrosides.

  • Isolation of cytotoxic glucoerebrosides and long-chain bases from sea cucumber Cucumaria frondosa using high speed counter-current chromatography.
    Journal of Oleo Science, 2013
    Co-Authors: Jie Xu, Yu Ming Wang, Lei Du, Tatsuya Sugawara, Takashi Hirata
    Abstract:

    Total Glucocerebrosides of the sea cucumber Cucumaria frondosa (CFC) have been isolated from the less polar lipid fraction of the chloroform-methanol extract using high speed counter-current chromatography (HSCCC) with a two-phase solvent system composed of petroleum ether-methanol-water (5:4:1, v/v). Three Glucocerebroside molecular species (CFC-1, CFC-2 and CFC-3) were isolated from crude total cerebrosides with repeated column chromatography. The structures of these three Glucocerebroside molecular species were determined on the basis of chemical and spectroscopic evidence: fatty acids were mainly saturated (C22:0 and C18:0), monounsaturated (C24:1 and C20:1) and α-hydroxyl fatty acids (C24:1h, C23:0h, C23:1h and C22:0h), the structures of long-chain bases were dihydroxy (d17:1, d18:2 and d18:1) and trihydroxy (t17:0 and t16:0), and the glycosylation was glucose. High purity long-chain bases of sea cucumber Cucumaria frondosa (CF-LCB) were prepared from total lipids by HSCCC with a two-phase solvent system composed of n-hexane-methyl tert butyl ether-methanol-water (1:1:2:1, v/v). Compare with traditional preparative methods, the method of HSCCC is short cycle, high yield and less solvent consumption. The composition analysis of CF-LCB showed that the ratio of d18:2 and d17:1 was approximately 2:1. The four Glucocerebrosides and long-chain bases from sea cucumber Cucumaria frondosa were evaluated for activity in vitro assays for the cytotoxic activities against Caco-2 colon cancer cells. The results indicated that both Glucocerebrosides and long-chain bases exhibited an inhibitory effect on cell proliferation. Moreover, CFC-3 was most effective in four Glucocerebrosides to Caco-2 cell viability. The inhibition effect of CF-LCB was much stronger than Glucocerebrosides.

  • three Glucocerebroside molecular species from the sea cucumber apostichopus japonicus
    Advanced Materials Research, 2012
    Co-Authors: Jie Xu, Yu Ming Wang, Pei Xu Cong
    Abstract:

    Three Glucocerebroside molecular species, AJC-1, AJC-2 and AJC-3, have been isolated from the less lipid fraction of the chloroform–methanol extract of the sea cucumber Apostichopus japonica by repeated column chromatography. The structures of these Glucocerebroside molecular species were determined on the basis of chemical and spectroscopic evidence. The composition of three Glucocerebrosides (AJC-1, AJC-2 and AJC-3): fatty acids were mainly saturated (C18:0), monounsaturated (C24:1) and α-hydroxyl fatty acids (C24:1h, C23:0h and C22:0h), the structures of long-chain base were dihydroxy (d18:2, d17:1 and d17:0) and trihydroxy (t17:0), and the glycosylation was mainly glucose. Three Glucocerebroside molecular species were evaluated for activity in vitro assays for the cytotoxic activities against human colonic cancer cell line (Caco-2).

  • analysis and comparison of Glucocerebroside species from three edible sea cucumbers using liquid chromatography ion trap time of flight mass spectrometry
    Journal of Agricultural and Food Chemistry, 2011
    Co-Authors: Jie Xu, Tatsuya Sugawara, Jingjing Duan, Tingyu Feng, Ping Dong, Takashi Hirata
    Abstract:

    Sphingolipids constitute a highly diverse and complex class of molecules and exhibit important physiological functions. Glucocerebrosides are anticipated to play a positive role in human nutrition. In this study, complicated Glucocerebrosides from three specimens of edible sea cucumbers, specifically, Acaudina molpadioides, Cucumaria frondosa, and Apostichopus japonicus, were rapidly identified using liquid chromatography–ion trap–time-of-flight mass spectrometry (LCMS-IT-TOF), which is a powerful analysis tool. [M + H]+, [M + Na]+, and [M + H – H2O]+ in positive electrospray ionization (ESI) mode were used for MS/MS analysis to obtain product ion spectra. Various long-chain bases of Glucocerebrosides were found in these sea cucumbers. Two of the most common long-chain bases were 2-amino-1,3-dihydroxy-4-heptadecene (d17:1) and 4,8-sphingadienine (d18:2), which were acylated to form saturated and monounsaturated nonhydroxy and monohydroxy fatty acids with 18–25 carbon atoms. The Glucocerebroside molecular ...

Ryuichi Higuchi - One of the best experts on this subject based on the ideXlab platform.

Takashi Hirata - One of the best experts on this subject based on the ideXlab platform.

  • Isolation of cytotoxic glucoerebrosides and long-chain bases from sea cucumber Cucumaria frondosa using high speed counter-current chromatography.
    Journal of Oleo Science, 2013
    Co-Authors: Jie Xu, Yu Ming Wang, Lei Du, Tatsuya Sugawara, Takashi Hirata
    Abstract:

    Total Glucocerebrosides of the sea cucumber Cucumaria frondosa (CFC) have been isolated from the less polar lipid fraction of the chloroform-methanol extract using high speed counter-current chromatography (HSCCC) with a two-phase solvent system composed of petroleum ether-methanol-water (5:4:1, v/v). Three Glucocerebroside molecular species (CFC-1, CFC-2 and CFC-3) were isolated from crude total cerebrosides with repeated column chromatography. The structures of these three Glucocerebroside molecular species were determined on the basis of chemical and spectroscopic evidence: fatty acids were mainly saturated (C22:0 and C18:0), monounsaturated (C24:1 and C20:1) and α-hydroxyl fatty acids (C24:1h, C23:0h, C23:1h and C22:0h), the structures of long-chain bases were dihydroxy (d17:1, d18:2 and d18:1) and trihydroxy (t17:0 and t16:0), and the glycosylation was glucose. High purity long-chain bases of sea cucumber Cucumaria frondosa (CF-LCB) were prepared from total lipids by HSCCC with a two-phase solvent system composed of n-hexane-methyl tert butyl ether-methanol-water (1:1:2:1, v/v). Compare with traditional preparative methods, the method of HSCCC is short cycle, high yield and less solvent consumption. The composition analysis of CF-LCB showed that the ratio of d18:2 and d17:1 was approximately 2:1. The four Glucocerebrosides and long-chain bases from sea cucumber Cucumaria frondosa were evaluated for activity in vitro assays for the cytotoxic activities against Caco-2 colon cancer cells. The results indicated that both Glucocerebrosides and long-chain bases exhibited an inhibitory effect on cell proliferation. Moreover, CFC-3 was most effective in four Glucocerebrosides to Caco-2 cell viability. The inhibition effect of CF-LCB was much stronger than Glucocerebrosides.

  • analysis and comparison of Glucocerebroside species from three edible sea cucumbers using liquid chromatography ion trap time of flight mass spectrometry
    Journal of Agricultural and Food Chemistry, 2011
    Co-Authors: Jie Xu, Tatsuya Sugawara, Jingjing Duan, Tingyu Feng, Ping Dong, Takashi Hirata
    Abstract:

    Sphingolipids constitute a highly diverse and complex class of molecules and exhibit important physiological functions. Glucocerebrosides are anticipated to play a positive role in human nutrition. In this study, complicated Glucocerebrosides from three specimens of edible sea cucumbers, specifically, Acaudina molpadioides, Cucumaria frondosa, and Apostichopus japonicus, were rapidly identified using liquid chromatography–ion trap–time-of-flight mass spectrometry (LCMS-IT-TOF), which is a powerful analysis tool. [M + H]+, [M + Na]+, and [M + H – H2O]+ in positive electrospray ionization (ESI) mode were used for MS/MS analysis to obtain product ion spectra. Various long-chain bases of Glucocerebrosides were found in these sea cucumbers. Two of the most common long-chain bases were 2-amino-1,3-dihydroxy-4-heptadecene (d17:1) and 4,8-sphingadienine (d18:2), which were acylated to form saturated and monounsaturated nonhydroxy and monohydroxy fatty acids with 18–25 carbon atoms. The Glucocerebroside molecular ...

Ernest Beutler - One of the best experts on this subject based on the ideXlab platform.

  • Reviews in Cell Biology and Molecular Medicine - Gaucher Disease, Molecular Biology of
    Reviews in Cell Biology and Molecular Medicine, 2006
    Co-Authors: Ernest Beutler
    Abstract:

    First page of article Keywords: Glucocerebroside; Glucocerebrosidase; Pyruvate kinase; Polymorphism; Pseudogene

  • polymorphisms in glucosylceramide Glucocerebroside synthase and the gaucher disease phenotype
    Israel Medical Association Journal, 2002
    Co-Authors: Ernest Beutler, Carol West
    Abstract:

    Background: Gaucher disease results from the accumulation of glucosylceramide (Glucocerebroside) in tissues of affected persons. Patients sharing the same genotype present with widely varying degrees of lipid storage and of clinical manifestations. Objectives: To determine whether variation in the glucosylceramide synthase (UDPGlucose ceramide glucosyltransferase) gene, which encodes the enzyme that regulates the synthesis of Glucocerebroside, could account for the variability and clinical manifestations. Methods: Patients homozygous for the 1226G (N370S) mutation, the most common in the Ashkenazi Jewish population, were investigated. The exons and flanking sequences of the gene were sequenced using DNA derived from five very mild Gaucher disease patients and four patients with relatively severe Gaucher disease. Results: One polymorphism was found in the coding region, but this did not change any amino acids. Seven other polymorphisms were found in introns and in the 5' untranslated region. Some of these were single nucleotide polymorphisms; others were insertions. The mutations appear to be in linkage equilibrium and none were found with a significantly higher frequency in either severe or mildly affected individuals. Conclusions: Mutations in the glucosylceramide synthase gene do not appear to account for the variability in expression of the common Jewish Gaucher disease mutation.

  • A chimeric mouse model of Gaucher disease.
    Molecular Medicine, 2002
    Co-Authors: Ernest Beutler, Carol West, Bruce E. Torbett, Hiroshi Deguchi
    Abstract:

    BACKGROUND: There is a major need for a mouse model of Gaucher disease, but the glucocerebrosidase knockout mouse is not viable; it dies shortly before or immediately after birth, apparently because of involvement of the central nervous system and/or skin. The most common form of Gaucher disease, type I, has a phenotype that is limited to the monocyte-macrophage system. MATERIALS AND METHODS: We have created a chimeric mouse by infusing hematopoietic stem cells from fetuses that are homozygous for the glucocerebrosidase knockout into irradiated mice. RESULTS: The chimeric mice manifested a severe deficiency of glucocerebrosidase activity in peripheral blood cells and spleen indicating a lack of cell-cell correction. Levels of Glucocerebroside in spleen and liver are increased, and infusing the mice with exogenous Glucocerebroside/albumin particles produced a marked increase in the amount of Glucocerebroside stored in liver and spleen. Morphologically identifiable Gaucher cells were not present. CONCLUSIONS: The chimeric model reflects the increased glycolipid storage in the reticuloendothelial system that is characteristic of Gaucher disease, and could be useful as a model for studying treatment of Gaucher disease.

  • A Chimeric Mouse Model of Gaucher Disease
    Molecular Medicine, 2002
    Co-Authors: Ernest Beutler, Carol West, Bruce E. Torbett, Hiroshi Deguchi
    Abstract:

    Background There is a major need for a mouse model of Gaucher disease, but the glucocerebrosidase knockout mouse is not viable; it dies shortly before or immediately after birth, apparently because of involvement of the central nervous system and/or skin. The most common form of Gaucher disease, type I, has a phenotype that is limited to the monocyte-macrophage system. Materials and Methods We have created a chimeric mouse by infusing hematopoietic stem cells from fetuses that are homozygous for the glucocerebrosidase knockout into irradiated mice. Results The chimeric mice manifested a severe deficiency of glucocerebrosidase activity in peripheral blood cells and spleen indicating a lack of cell-cell correction. Levels of Glucocerebroside in spleen and liver are increased, and infusing the mice with exogenous Glucocerebroside/albumin particles produced a marked increase in the amount of Glucocerebroside stored in liver and spleen. Morphologically identifiable Gaucher cells were not present. Conclusions The chimeric model reflects the increased glycolipid storage in the reticuloendothelial system that is characteristic of Gaucher disease, and could be useful as a model for studying treatment of Gaucher disease.

Rachel Levy - One of the best experts on this subject based on the ideXlab platform.

  • monocyte dysfunction in patients with gaucher disease evidence for interference of Glucocerebroside with superoxide generation
    Blood, 1994
    Co-Authors: Yair Liel, Assaf Rudich, Ofra Nagaukershriker, Tikva Yermiyahu, Rachel Levy
    Abstract:

    Gaucher disease patients are occasionally affected by chronic or fulminant infections. Since Gaucher cells originate from tissue phagocytes, we studied the functional implications of glucocerbroside accumulation on phagocytes in Gaucher disease patients. Circulating monocytes and granulocytes from nine type I Gaucher disease patients, and matched controls, were studied. Evaluation of phagocytic activity included (1) maximal superoxide generation rates following stimulation by phorbol 12-myristate 13-acetate (PMA), opsonized zymosan (OZ), or formyl-methionyl-leucylphenylalanine (FMLP); (2) nitroblue tetrazolium reduction test (NBT); (3) chemotaxis toward FMLP; (4) phagocytosis of OZ particles; and (5) killing activity against Staphylococcus aureus. Superoxide generation in monocytes following PMA, OZ, and FMLP stimulation was significantly suppressed at 52% +/- 15%, 39% +/- 8%, and 51% +/- 11% of control, respectively. Superoxide generation in granulocytes was normal. NBT reduction, staphylococcal killing, and phagocytosis were also markedly decreased in monocytes, and normal in granulocytes. Mean chemotaxis rates were normal in both monocytes and granulocytes; however, decreased chemotactic rates were observed in some patients. The abnormality of superoxide generation could be reproduced in a dose- and time-dependent manner in normal circulating monocytes incubated with Glucocerebroside. Superoxide generation in Glucocerebroside-conditioned normal monocytes in a cell-free system showed normal superoxide generation, reflecting the integrity of the NADPH oxidase complex itself. These results demonstrate markedly compromised phagocytic functions in circulating monocytes in Gaucher disease patients. These abnormalities can be attributed to accumulation of Glucocerebroside, since it could be reproduced in normal monocytes incubated with Glucocerebroside. Similar abnormalities in Gaucher cells throughout the reticuloendothelial system could impair host defense, and may be of particular importance in the pathogenesis of osteomyelitis in Gaucher disease patients.

  • Monocyte dysfunction in patients with Gaucher disease: evidence for interference of Glucocerebroside with superoxide generation [see comments]
    Blood, 1994
    Co-Authors: Yair Liel, Assaf Rudich, Tikva Yermiyahu, O Nagauker-shriker, Rachel Levy
    Abstract:

    Abstract Gaucher disease patients are occasionally affected by chronic or fulminant infections. Since Gaucher cells originate from tissue phagocytes, we studied the functional implications of glucocerbroside accumulation on phagocytes in Gaucher disease patients. Circulating monocytes and granulocytes from nine type I Gaucher disease patients, and matched controls, were studied. Evaluation of phagocytic activity included (1) maximal superoxide generation rates following stimulation by phorbol 12-myristate 13-acetate (PMA), opsonized zymosan (OZ), or formyl-methionyl-leucylphenylalanine (FMLP); (2) nitroblue tetrazolium reduction test (NBT); (3) chemotaxis toward FMLP; (4) phagocytosis of OZ particles; and (5) killing activity against Staphylococcus aureus. Superoxide generation in monocytes following PMA, OZ, and FMLP stimulation was significantly suppressed at 52% +/- 15%, 39% +/- 8%, and 51% +/- 11% of control, respectively. Superoxide generation in granulocytes was normal. NBT reduction, staphylococcal killing, and phagocytosis were also markedly decreased in monocytes, and normal in granulocytes. Mean chemotaxis rates were normal in both monocytes and granulocytes; however, decreased chemotactic rates were observed in some patients. The abnormality of superoxide generation could be reproduced in a dose- and time-dependent manner in normal circulating monocytes incubated with Glucocerebroside. Superoxide generation in Glucocerebroside-conditioned normal monocytes in a cell-free system showed normal superoxide generation, reflecting the integrity of the NADPH oxidase complex itself. These results demonstrate markedly compromised phagocytic functions in circulating monocytes in Gaucher disease patients. These abnormalities can be attributed to accumulation of Glucocerebroside, since it could be reproduced in normal monocytes incubated with Glucocerebroside. Similar abnormalities in Gaucher cells throughout the reticuloendothelial system could impair host defense, and may be of particular importance in the pathogenesis of osteomyelitis in Gaucher disease patients.