• Title/Summary/Keyword: Sphingolipids

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Profiling Analysis of Sphingolipids in HL-60 Cells by High-Performance Liquid Chromatography-Tandem Mass Spectrometry in combination with Multiple Reaction Monitoring

  • Son, Jung-Hyun;Lee, Jae-Ick;Yang, Ryung;Kim, Dong-Hyun
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.288.3-289
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    • 2003
  • Sphingolipid species are important second messengers due to their role in the mitogenesis, differentiation and apoptosis. We developed a new column liquid chromatography-triple quadrupole tandem mass spectrometry (LC-MS/MS) in combination with multiple reaction monitoring (MRM) method for the rapid, simultaneous and quantitative determination of unambiguous detecting sphingolipids in cell culture of human cancer cells (HL-60). (omitted)

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The altered $Na^+,\;K^+$-pump activity following the fumonisin exposure to LLC-PKl cells

  • Choi, Heon-Kyo;Yoo, Jae-Myung;Tudev, Munkhtsetseg;Lee, Yong-Moon;Yun, Yeo-Pyo;Yoo, Hwan-Soo
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.110.1-110.1
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    • 2003
  • Fumonisins are specific inhibitors of ceramide synthase in sphingolipid metabolism. Sphingolipids are biologically active lipid mediators in cellular physiology and involved in cell signaling, growth, transformation, angiogenesis and differentiation. The objective of this study was to determine the effect of fumonisin B1 on $Na^+, \;K^+$-pump activity when fumonisin B1 was exposed to LLC-PK1 cells. Fumonisin B1 elevated free sphingoid bases and their 1-phosphates, while total complex sphingolipids were depleted at 20$\mu$M fumonisin B1 during the 3 day exposure. (omitted)

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Inhibition of GM3 Synthase Attenuates Neuropathology of Niemann-Pick Disease Type C by Affecting Sphingolipid Metabolism

  • Lee, Hyun;Lee, Jong Kil;Bae, Yong Chul;Yang, Song Hyun;Okino, Nozomu;Schuchman, Edward H.;Yamashita, Tadashi;Bae, Jae-Sung;Jin, Hee Kyung
    • Molecules and Cells
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    • v.37 no.2
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    • pp.161-171
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    • 2014
  • In several lysosomal storage disorders, including Niemann-Pick disease Type C (NP-C), sphingolipids, including glycosphingolipids, particularly gangliosides, are the predominant storage materials in the brain, raising the possibility that accumulation of these lipids may be involved in the NP-C neurodegenerative process. However, correlation of these accumulations and NP-C neuropathology has not been fully characterized. Here we derived NP-C mice with complete and partial deletion of the Siat9 (encoding GM3 synthase) gene in order to investigate the role of ganglioside in NP-C pathogenesis. According to our results, NP-C mice with homozygotic deletion of GM3 synthase exhibited an enhanced neuropathological phenotype and died significantly earlier than NP-C mice. Notably, in contrast to complete depletion, NP-C mice with partial deletion of the GM3 synthase gene showed ameliorated NP-C neuropathology, including motor disability, demyelination, and abnormal accumulation of cholesterol and sphingolipids. These findings indicate the crucial role of GM3 synthesis in the NP-C phenotype and progression of CNS pathologic abnormality, suggesting that well-controlled inhibition of GM3 synthesis could be used as a therapeutic strategy.

Disruption of Sphingolipid Metabolism as a Potential Mechanism of Fumonisin Inhibition of Cell Growth in $LLC-PK_1$ Cells

  • Yoo, Hwan-Soo;Yun, Yeo-Pyo
    • Toxicological Research
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    • v.11 no.1
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    • pp.1-8
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    • 1995
  • Fumonisins are a family of mycotoxins produced by the fungus Fusarium moniliforme which is a common contaminant in corn. Fumonisins are potent inhibitors of sphingosine and sphinganine N-acyltransferase (ceramide synthase), key enzymes in sphingolipid metabolism. The purpose of this study was to provide the evidence that the elevated levels of free sphingoid bases (primarily sphinganine) and depletion of complex sphingolipids were closely related to the inhibition of cell growth in LLC-$PK_1$ cells exposed to fumonisin $B_1$$(\leq 35 {\mu}M)$. Concentrations of fumonisin $B_1$ between 10 and $35 {\mu}M$ were known to inhibit cell growth without cytotoxicity in $LLC-PK_1$ cells (Yoo et al. Toxicol. Appl. Pharmacol. 114, 9-15, 1992). Cells exposed to 35$\mu M$ fumonisin B$_1$ for 48 and 72 hr developed a fibroblast-like (elongated and spindle-shaped) appearance and were less confluent than normal cells. At between 24 and 48 hr after exposure to fumonisin $B_1$ cells were beginning to show the inhibition of cell growth and at 72 hr the number of viable cells in fumonisin-treated cultures was about 50% of concurrent control cultures. During the 24 hr lag period preceding inhibition of cell growth, the free sphinganine levels in cells exposed to $35 {\mu}M$ fumonisin $B_1$ were highly elevated (approximately 230 fold higher than normal cells). The elevated levels of free sphinganine were $435\pm14$$pmoles/{10^6}$ cells at 48 hr and approximately TEX>$333\pm11$$pmoles/{10^6}$ cells in cells exposed to $35{\mu}M$ fumonisin$B_1$ at 72 hr, while the levels of free sphinganine in normal cells were less than 2$pmoles/{10^6}$ cells. Under the same condition, depletion of intracellular complex sphingolipids as a consequence of fumonisin inhibition of de novo sphingolipid biosynthesis and turnover pathway was appeared. Content of free sphingold bases in dividing cells was more elevated than in confluent cells at 24-48 hr after cells were exposed to $20{\mu}M$ fumonisin $B_1$. The dividing cells were showing the inhibition of cell growth at 48-72 hr and $20{\mu}M$ fumonisin $B_1$. The results of this study support the hypothesis that the inhibition of cell growth is very well related to the disruption of sphingolipid metabolism in $LLC-PK_1$ cells.

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Production of Sphingolipids by Submerged Culture of Ganoderma lucidum and Cutaneous Hydration Effect (Ganoderma lucidum 균사체의 액체배양의 의한 sphingolipids의 생산 및 피부 보습 효과)

  • Ryu, Il-Hwan;Kim, Jung-Enn;Lee, Kap-Sang
    • Korean Journal of Food Science and Technology
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    • v.36 no.4
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    • pp.655-661
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    • 2004
  • Sphingolipid production was investigated through Ganoderma lucidum-submerged cultivation. Crude sphingolipid obtained from G. lucidum was purified by methanol precipitation, Dowex AG DW-X8 (H+ form) cation exchange chromatography, and preparative thin layer chromatography, Structure and functionalities of purified sphingolipid were elucidated including cutaneous hydration effect. Possibility of use as cosmetics material and new biomaterial was explored. Production was 0.4 g/L at 1% yield. Purified sphingolipid was identified as D-ribo-1,3,4-trihydroxy-2-aminoocta decan through UV/VIS, FT-IR, and $^1H-NMR$. Sphingolipids increased skinmate value for cutaneous hydration effect by 20% at $500\;{\mu}g/mL$ and decreased skin roughness at $100\;{\mu}g/mL$. Results suggest shingolipids from G. lucidum are effective for cutaneous hydration and improvement of skin roughness.

Links between accelerated replicative cellular senescence and down-regulation of SPHK1 transcription

  • Kim, Min Kyung;Lee, Wooseong;Yoon, Gang-Ho;Chang, Eun-Ju;Choi, Sun-Cheol;Kim, Seong Who
    • BMB Reports
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    • v.52 no.3
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    • pp.220-225
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    • 2019
  • We have identified a mechanism to diminish the proliferative capacity of cells during cell expansion using human adipose-derived stromal cells (hAD-SCs) as a model of replicative senescence. hAD-SCs of high-passage numbers exhibited a reduced proliferative capacity with accelerated cellular senescence. Levels of key bioactive sphingolipids were significantly increased in these senescent hAD-SCs. Notably, the transcription of sphingosine kinase 1 (SPHK1) was down-regulated in hAD-SCs at high-passage numbers. SPHK1 knockdown as well as inhibition of its enzymatic activity impeded the proliferation of hAD-SCs, with concomitant induction of cellular senescence and accumulation of sphingolipids, as seen in high-passage cells. SPHK1 knockdown-accelerated cellular senescence was attenuated by co-treatment with sphingosine-1-phosphate and an inhibitor of ceramide synthesis, fumonisin $B_1$, but not by treatment with either one alone. Together, these results suggest that transcriptional down-regulation of SPHK1 is a critical inducer of altered sphingolipid profiles and enhances replicative senescence during multiple rounds of cell division.

The ceramide contents of Saccharomyces cerevisiae in batch culture (Saccharomyces cerevisiae 의 회분식 배양에서 세라마이드의 생산)

  • Kim, Se-Kyung;Noh, Yong-Ho;Yun, Hyun-Shik
    • KSBB Journal
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    • v.23 no.5
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    • pp.449-451
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    • 2008
  • Ceramide has become a widely used ingredient in cosmetic and pharmaceutical industries, however, only a few yeast strains were investigated for the synthesis of ceramide and the concentration was very low. Ceramide is not only a core intermediate of sphingolipids but also an important modulator of many cellular events including apoptosis, cell cycle arrest, senescence, differentiation, and stress responses. In this study S.cerevisiae was grown in a batch culture and the cellular content of ceramide was measured at different growth phases. The ceramide content was highest at stationary phase and 2.01 mg ceramide/g cell was obtained.