• 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.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.6
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• pp.441-447
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• 2010

B13, a ceramide analogue, is a ceramidase inhibitor and induces apoptosis to give potent anticancer activity. A series of thiourea B13 analogues was evaluated for their in vitro cytotoxic activities against human renal cancer Caki-2 and leukemic cancer HL-60 in the MTT assay. Some compounds (12, 15, and 16) showed stronger cytotoxicity than B13 and C6-ceramide against both tumor cell lines, and compound (12) gave the most potent activity with $IC_{50}$ values of 36 and $9\;{\mu}M$, respectively. Molecular modeling of thiourea B13 analogues was carried out by comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). We obtained highly reliable and predictive CoMSIA models with cross-validated $q^2$ values of 0.707 and 0.753 and CoMSIA contour maps to show the structural requirements for potent activity. These data suggest that the amide group of B13 could be replaced by thiourea, that the stereochemistry of 1,3-propandiol may not be essential for activity and that long alkyl chains increase cytotoxicity.

• Journal of Integrative Natural Science
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• v.6 no.3
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• pp.125-137
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• 2013

Promising evidence suggests that amyloid beta peptide ($A{\beta}$), a key mediator in age-dependent neuronal and cerebrovascular degeneration, activates death signalling processes leading to neuronal as well as non-neuronal cell death in the central nervous system. A major cellular event in $A{\beta}$-induced apoptosis of non-neuronal cells, including cerebral endothelial cells, astrocytes and oligodendrocytes, is mitochondrial dysfunction. The apoptosis signalling cascade upstream of mitochondria entails $A{\beta}$ activation of neutral sphingomyelinase, resulting in the release of ceramide from membrane sphingomyelin. Ceramide then activates protein phosphatase 2A (PP2A), a member in the ceramide-activated protein phosphatase (CAPP) family. PP2A dephosphorylation of Akt and FKHRL1 plays a pivotal role in $A{\beta}$-induced Bad translocation to mitochondria and transactivation of Bim. Bad and Bim are pro-apoptotic proteins that cause mitochondrial dysfunction characterized by excessive ROS formation, mitochondrial DNA (mtDNA) damage, and release of mitochondrial apoptotic proteins including cytochrome c, apoptosis inducing factor (AIF), endonuclease G and Smac. The cellular events activated by $A{\beta}$ to induce death of non-neuronal cells are complex. Understanding these apoptosis signalling processes will aid in the development of more effective strategies to slow down age-dependent cerebrovascular degeneration caused by progressive cerebrovascular $A{\beta}$ deposition.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.3 s.47
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• pp.419-426
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• 2004

The nano-ceramide capsulation is a technique that capsulates ceramide III and tocopheryl linoleate at the mono-vesicle to act on the horny layer in skin. In this technique, $0.5{\~}5.0\;wt\%$ of hydrogenated lecithin and $0.01{\~}2.00\;wt\%$ of lysolecithin are used as the membrane-strengthen agents of the mono-vesicle and $5.0{\~}10.0\;wt\%$ of propylene glycol and $5.0{\~}10.0\;wt\%$ of ethyl alcohol are used as solvents. Active ingredients such ceramide III and tocopheryl linoleate are utilized to enhance the moisturizing efficacy and treat atopy skin. These materials do not contain synthetic emulsifiers. The optimal conditions or nano-ceramide capsulation are such that particles pass Microfludizdizer 3 times at 1,000 bar and $60{\~}70^{\circ}C$ and pH of nano capsules is $5.8{\pm}0.5.$ The average size of particles is $63.1{\pm}7.34\;nm$ showing lucid state like water by the laser light scattering. A zeta potential value is $-55.1\pm0.84\;mV.$ Through clinical tests, the moisturizing effect (in-vivo, n=8, p-value<0.05) showed $21.15\%$ of improvement comparison to comparison-samples and $36.31\%$ of improvement compared to the state before treatment. Moreover, the effectiveness of atopy skin showed positive reaction from 10 volunteers.

• Proceedings of the PSK Conference
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• 2001.04a
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• pp.99.1-99.1
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• 2001

• The Zoological Society Korea : Newsletter
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• v.12 no.2
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• pp.129.1-129
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• 1995

No Abstract, See Full Text

• Proceedings of the Zoological Society Korea Conference
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• 1995.10b
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• pp.342.2-342
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• 1995

No Abstract, See Full Text

• Proceedings of the SCSK Conference
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• 2003.09b
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• pp.268-279
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• 2003

The nano capsulation of the ceramide was a technique that capsulated ceramide III and tocopheryl linoleate at the mono-vesicle, so as to act the horny layer in skin. It was used 0.5-5.0 wt% of hydrogenated lecithin and 0.01~2.00 wt% of lysolecithin as the membrane-strengthen agents of the mono-vesicle, 5.0~10 wt% of propylene glycol and 5.0~10.0 wt% of ethyl alcohol made by high-pressure Microfluidizer. To enhance the moisturizing efficacy and treat an atopy skin, used ceramide III and tocopheryl linoleate as the active ingredients, and it was made the nano-capsule that synthetic emulsifiers were free. The optimal condition of capsulation of nano ceramide was as follows. The conditions were 3 times at 1,000bar and 60-7$0^{\circ}C$. The particle size showed 63.1$\pm$7.34 nm such as the transparence water as the results for measuring by the laser light scattering. A zeta potential value was -55.1$\pm$0.84 ㎷. The result of the clinical test, the moisturizing effect (in-vivo, n=8, p-value<0.05) was improved 21.15% compared to control, as well as it was improved 36.31 % before the treatment. Moreover, the effectiveness of atopy skin indicated positive reaction that patients were 10 volunteers.

• Nutrition Research and Practice
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• v.10 no.4
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• pp.398-403
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• 2016

BACKGROUND/OBJECTIVES: Atopic dermatitis (AD), a chronic inflammatory skin disease, is accompanied by disruption of the epidermal lipid barrier, of which ceramide (Cer) is the major component. Recently it was reported that vitamin C is essential for de novo synthesis of Cer in the epidermis and that the level of vitamin C in plasma is decreased in AD. The objective of this study was to determine the associations among clinical severity, vitamin C in either plasma or epidermis, and Cer in the epidermis of patients with AD. SUBJECTS/METHODS: A total of 17 patients (11 male and 6 female) aged 20-42 years were enrolled. The clinical severity of AD was assessed according to the SCORAD (SCORing Atopic Dermatitis) system. Levels of vitamin C were determined in plasma and biopsies of lesional epidermis. Levels of epidermal lipids, including Cer, were determined from tape-stripped lesional epidermis. RESULTS: The clinical severity of patients ranged between 0.1 and 45 (mild to severe AD) based on the SCORAD system. As the SCORAD score increased, the level of vitamin C in the plasma, but not in the epidermis, decreased, and levels of total Cer and Cer2, the major Cer species in the epidermis, also decreased. There was also a positive association between level of vitamin C in the plasma and level of total Cer in the epidermis. However, levels of epidermal total lipids including triglyceride, cholesterol, and free fatty acid (FFA) were not associated with either SCORAD score or level of vitamin C in the plasma of all subjects. CONCLUSIONS: As the clinical severity of AD increased, level of vitamin C in the plasma and level of epidermal Cer decreased, and there was a positive association between these two parameters, implying associations among plasma vitamin C, epidermal Cer, and the clinical severity of AD.