• Journal of Life Science
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• v.22 no.6
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• pp.760-771
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• 2012

Marine triterpene glycosides are physiologically active natural compounds isolated from sea cucumbers(holothurians). It was demonstrated that they have a wide range of biological activities, including antifungal, cytotoxic, and antitumor effects. A previous study showed that stichoposide C (STC) isolated from Thelenota anax induces apoptosis through generation of ceramide by activation of acid sphingomyelinase (SMase) and neutral SMase in human leukemia cells. In this study, we investigated whether STD, a structural analog of STC, can induce apoptosis and examined the molecular mechanisms for its activity. It was found that STC and STD induce apoptosis in a dose- and time-dependent manner and lead to the activation of caspase-8, mitochondrial damage, activation of caspase-9, and activation of caspase-3 in K562 and HL-60 cells. STC activates acid SMase and neutral SMase, which results in the generation of ceramide. Specific inhibition of acid SMase or neutral SMase partially blocked STC-induced apoptosis, but not STD-induced apoptosis. In contrast, STD generates ceramide through the activation of ceramide synthase. Specific inhibition of ceramide synthase partially blocked STD-induced apoptosis, but not STC-induced apoptosis. Moreover, STC and STD markedly reduced tumor growth of HL-60 xenograft tumors and increased ceramide generation in vivo. These results indicate that STC and STD can induce apoptosis and have antitumor activity through the different molecular mechanisms, because they have a different sugar residue attached to aglycones. Thus, these results suggest that their actions are affected by a sugar residue attached to aglycones and they can be used as anticancer agents in the treatment of leukemia.

• Journal of Life Science
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• v.9 no.2
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• pp.160-168
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• 1999

Butyrate is one of the short-chain fatty acids that are present in the colon of mammals in millimolar concentration as a result of microbial anaerobic fermentation of dietary fiber, undigested starch, and proteins. In this study, sodium butyrate was examined in HT29 cell, human colonic cancer cell line, on cell viability, alkaline phosphatase activity, PLC-${\gamma}$1 expression and complex sphingolipid biosynthesis. Treatment with butyrate showed that the decrease of cell adhesion and viability was time-dependent. Sodium butyrate also induced to increase the activity of alkaline phosphatase which is a differentiation marker enzyme and decrease the expression of PLC-${\gamma}$1. Biosynthesis of sphingomyelin and galactosylceramide by butyrate treatment were decreased so fast but ceramide was increased 680dpm/mg protein% more than untreated group on first day and then decreased fast. In addition, acid ceramidase and neutral ceramidase activity were inhibited early stage by sodium butyrate. These results suggest that sodium butyrate causes cell differentiation or cell growth arrest of HT29 cell accompanied by early increase of ceramide content and alkaline phosphatase activity and decrease of galactosylceramide content and PLC-r1 expression.

• BMB Reports
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• v.37 no.2
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• pp.185-191
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• 2004

Tissue transglutaminase (tTGase) regulates various biological processes, including extracellular matrix organization, cellular differentiation, and apoptosis. Here we report the protective role of tTGase in the cell death that is induced by the tumor necrosis factor $\alpha$ (TNF-$\alpha$) and ceramide, a product of the TNF-$\alpha$ signaling pathway, in human neuroblastoma SH-SY5Y cells. Treatment with retinoic acid (RA) induced the differentiation of the neuroblastoma cells with the formation of extended neurites. Immunostaining and Western blot analysis showed the tTGase expression by RA treatment. TNF-$\alpha$ or $C_2$ ceramide, a cell permeable ceramide analog, induced cell death in normal cells, but cell death was largely inhibited by the RA treatment. The inhibition of tTGase by the tTGase inhibitors, monodansylcadaverine and cystamine, eliminated the protective role of RA-treatment in the cell death that is caused by TNF-$\alpha$ or $C_2$-ceramide. In addition, the co-treatment of TNF-$\alpha$ and cycloheximide ecreased the protein level of tTGase and cell viability in the RA-treated cells, supporting the role of tTGase in the protection of cell death. DNA fragmentation was also induced by the co-treatment of TNF-$\alpha$ and cycloheximide. These results suggest that tTGase expressed by RA treatment plays an important role in the protection of cell death caused by TNF-$\alpha$ and ceramide.

• Molecules and Cells
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• v.46 no.11
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• pp.688-699
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• 2023

We set up this study to understand the underlying mechanisms of reduced ceramides on immune cells in acute rejection (AR). The concentrations of ceramides and sphingomyelins were measured in the sera from hepatic transplant patients, skin graft mice and hepatocyte transplant mice by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Serum concentrations of C24 ceramide, C24:1 ceramide, C16:0 sphingomyelin, and C18:1 sphingomyelin were lower in liver transplantation (LT) recipients with than without AR. Comparisons with the results of LT patients with infection and cardiac transplant patients with cardiac allograft vasculopathy in humans and in mouse skin graft and hepatocyte transplant models suggested that the reduced C24 and C24:1 ceramides were specifically involved in AR. A ceramide synthase inhibitor, fumonisin B₁ exacerbated allogeneic immune responses in vitro and in vivo, and reduced tolerogenic dendritic cells (tDCs), while increased P3-like plasmacytoid DCs (pDCs) in the draining lymph nodes from allogeneic skin graft mice. The results of mixed lymphocyte reactions with ceranib-2, an inhibitor of ceramidase, and C24 ceramide also support that increasing ceramide concentrations could benefit transplant recipients with AR. The results suggest increasing ceramides as novel therapeutic target for AR, where reduced ceramides were associated with the changes in DC subsets, in particular tDCs.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.11a
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• pp.144-144
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• 2002

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.328.1-328.1
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• 2002

A major lipid-signaling pathway in mammalian cells implicated the activation of sphingomyelinase (SMase), which hydrolyses sphingomyeline to generate ceramide and phosphocholine. Sphingomyelinase is divided into many isoform groups dependent on optimal pH, and essential cation especially magnesium in their activation. Such as acidic sphingomyelinase, neutral sphingomyelinase and alkaline sphingomyelinase. Ceramide is known as a crucial second messenger in cell responses like cell proliferation. cell cycle arrest. cellular senescence, and apoptosis. (omitted)

• Applied Chemistry for Engineering
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• v.21 no.6
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• pp.603-609
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• 2010

This paper aims to investigate the lyotropic behaviors of DSPC and CER3 when they are swollen by GLY as a solvent. The analyses were carried out on DSC, XRDs, PM, and Cryo-SEM. CER3 which has its high crystallinity and structural similarity with DSPC was well arranged up to 7.0 wt% in comparison to 20 wt% DSPC without any separation, but it was separated from the liquid crystalline (LC) phase to form another crystalline phase with the expression of its characteristic peak in XRDs and eutectic thermal behavior in DSC. Introducing CER3, two types of patterns were shown in XRD spectra; one is SPP expressed in a normal LC and another is LPP expressed in human skin SC. Therefore, it was confirmed that the incorporation of CER3 makes LC structure more similar to human skin. In Cryo-SEM study, it was shown that CER3 makes LC structure thicker and denser.

• Korean Journal of Community Nutrition
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• v.11 no.1
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• pp.63-71
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• 2006

The objective of this study was to evaluate whether nutrient intakes and serum biochemical indices are associated with the skin condition of humans. Anthropometric data, skin surface hydration, ceramide content, dietary intake of nutrients and serum lipids (total cholesterol, HDL-, LDL-cholesterol, TG, MDA: malondialdehyde, TAS: total antioxidant status) were obtained from 36 healthy young women. Subjects were classified into 2 groups {LM: Low Moisture Group (n = 20) , HM: High Moisture Group (n = 16)} by forehead skin hydration. The results of this study were as follows: The average age, BMI, total body water, LBM, body fat$\%$, WHR, forehead hydration, ceramide content were 20.2 yrs, 20.7, 28.81, 39.2 kg, $28.0\%$, 0.8, $44.3\%$, and 1.05 $\mu$g/$\mu$g protein, repectively. The intakes of SF A (saturated fatty acid) , MUFA (monounsaturated fatty acid) in the HM group were significantly higher (p < 0.05) than in the LM group, but zinc intakes in the LM group were higher than in the HM group. Serum levels of TAS in the LM group (1.27 mmol/l) were significantly higher (p < 0.05) than that of in the HM group (1.20 mmol/l). Whereas other lipid levels were not significantly different, intakes of vitamin $B_{6}$ and folate showed significant positive correlation with the forehead hydration (r = 0.447, r = 0.377). Intakes of calcium and phosphorus showed significant negative correlation with forearm ceramide content (r = -0.496, r = -0.485). Several associations between nutrient intakes and skin conditions were observed, indicating that changes in baseline nutritional status may affect skin health.

• Korean Journal of Veterinary Research
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• v.44 no.2
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• pp.233-239
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• 2004

This study was designed to quantitative assay of cellular receptor globotriosyl ceramide($Gb_3$) and globotetraosyl ceramide($Gb_4$) and to determine binding affinity of the receptors for Shigatoxin 2e in difference with day olds of pig. The amount of $Gb_3$ and $Gb_4$ extracted from each swine tissue were detected in order of spleen, ileocecum, kidney, and jejunum. The amount of $Gb_3$ and $Gb_4$ extracted from each swine ileocecum and jejunum in different day old swine were detected in order of 24, 6, 98, 12 and 35, but the difference of amount was not significant. The binding affinity of $Gb_4$ extracted from ileocecum and jejunum with different day old swine for Stx2e were shown that the extracts of 24, 12, and 35 days old swine were higher significantly than that of 6 and 98 days old swine.

• Applied Chemistry for Engineering
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• v.32 no.5
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• pp.541-546
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• 2021

Hydrated liquid crystalline vesicles containing a high content of ceramide were prepared by constituting an optimal composition in which ceramides can be mutually self-associated with phospholipid and cholesterol. From the result of manufacturing various vesicles with different component composition, when the edge activator sodium deoxycholate (SDOC) and the solubilizer PEG-60 hydrogenated castor oil (HCO 60) were mixed to form vesicles, the smallest nano-sized particles were produced and the vesicle dispersion solution was weakly acidic and maintained the most stable state. In addition, it was confirmed through polarized light microscopy and thermal analysis that the addition of SDOC and HCO 60 had an effect on the inhibition of crystallinity of lipid components such as ceramide. The stability of the vesicle dispersion solution was maintained without change in appearance and viscosity even after long-term storage at high temperature for eight weeks.