• 한국식품과학회지
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• 제36권4호
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• pp.655-661
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• 2004

Ganoderma lucidum 균사체의 액체 배양을 통하여 균체 내 sphingolipid를 분리 정제하여 그 구조를 규명하였으며, 피부보습을 비롯한 각종의 기능성을 탐색하여 화장품 소재 및 새로운 생물 산업소재의 이용가능성을 검토한 결과 배양한 Ganoderma lucidum로부터 일련의 과정을 통하여 crude sphingolipids를 얻고, methanol침전, Dowex AG $50W-X8(H^+\;form)$ cation exchange chromatography 및 preparative thin layer chromatography를 행하여 sphingolipids를 분리하였다. 생산량은 0.4g/L였으며, 수율은 1%였다. UV/VIS spectrum, FT-IR 및 1H-NMR 분석을 행하여 구조를 해석한 결과 phytosphingosine 유도체로 판명되었다. 이 phytosphingosine 유도체의 피부에 대한 보습효과는 $500{\mu}g/mL$ 이상의 농도에서 약 20% 정도 skinmate 값이 증가하였으며, $100{\mu}/mL$ 이상의 농도에서 거칠기 감소에 유의한 결과를 나타내었다. 이상의 결과로부터 Ganoderma lucidum이 생산하는 sphingolipids는 피부보습 및 거칠기 개선에 유의성이 확인되어 화장품 소재 및 새로운 생물 산업소재로서의 이용가능성이 높다고 할 수 있다.

• BMB Reports
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• 제50권3호
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• pp.144-149
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• 2017

Ceramides are the major sphingolipid metabolites involved in cell survival and apoptosis. When HepG2 hepatoma cells were treated with celecoxib, the expression of the genes in de novo sphingolipid biosynthesis and sphingomyelinase pathway was upregulated and cellular ceramide was elevated. In addition, celecoxib induced endoplasmic reticulum (ER) stress in a time-dependent manner. SPTLC2, a subunit of serine palmitoyltransferase, was overexpressed by adenovirus. Adenoviral overexpression of SPTLC2 (AdSPTLC2) decreased cell viability of HEK293 and HepG2 cells. In addition, AdSPTLC2 induced apoptosis via the caspase-dependent apoptotic pathway and elevated cellular ceramide, sphingoid bases, and dihydroceramide. However, overexpression of SPTLC2 did not induce ER stress. Collectively, celecoxib activates de novo sphingolipid biosynthesis and the combined effects of elevated ceramide and transcriptional activation of ER stress induce apoptosis. However, activation of de novo sphingolipid biosynthesis does not activate ER stress in hepatoma cells and is distinct from the celecoxib-mediated activation of ER stress.

• Biomolecules & Therapeutics
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• 제16권3호
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• pp.243-248
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• 2008

In the present study, we investigated activity change of sphingomyelin anabolic enzymes such as sphingomyelin synthase and ceramide synthase. Sprague-Dawley male rats treated with 10 mg/kg of DMN intraperitoneally were used as a hepatic fibrosis model. Sphingomyelin synthase and ceramide synthase activities were measured in 1-week, 2-week, 3-week and 4-week DMN-treated rats along with respective control group rats. We found the increased sphingomyelin synthase activity in 4-week DMN-treated liver but not in kidney. Ceramide synthase activity was significantly increased in DMN-treated kidney after 2-week treatment and in DMN-treated liver after 3-week treatment. Although further investigation is necessary to elucidate meanings of sphingolipid metabolites during the liver fibrosis, activity change of sphingolipid anabolic enzymes may imply that sphingolipid metabolism and sphingolipid metabolites could be involved in liver fibrosis especially under oxidative stress.

• 약학회지
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• 제43권1호
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• pp.61-67
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• 1999

Geranyllinalool, a polyisoprenoid compound, was found to block the early biosynthetic pathway of sphingolipids in LLC-PKl cells. Sphinganine, an intermediate in sphingolipid biosynthetic pathway, was abruptly accumulated in LLC-PKl cells at $2{\;}{\mu}M$ of fumonisin B1(FB1), a specific inhibitor of sphinganine N-acyltransferase, for 24 hr. Geranyllinalool lowered the $B_1(FB_1)$, a specific inhibitor of sphinganine N-acyltransferase, for 24 hr. Geranyllinalool lowered th FB1 and $50{\;}\mu$M geranyllinalool. l-Cy-closerine, an inhibitor of serine-palmitoyl transferase, was used as a positive control to evaluate the inhibitory effect of geranyllinalool. These results suggest that geranyllinalool may inhibit the serine-palmitoyl transferase, the first enzyme in de novo sphingolipid biosynthesis, resulting in the altered regulation of sphingolipid metabolism.

• 식품기술
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• 제22권1호
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• pp.31-40
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• 2009

• Biomolecules & Therapeutics
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• 제16권2호
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• pp.100-105
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• 2008

The sphingolipid metabolites act as lipid mediator for cell proliferation and apoptosis in mammalian cells. In bacteria, sphingolipid metabolism remains unknown. The purpose of this study was to investigate whether sphingolipid metabolism is potential target for fumonisin $B_1$($FB_1$) and desipramine in Sphingomonas chungbukensis, Gram-negative bacteria, by comparing the intracellular contents of bacterial sphingolipids with ones of HIT-T15 ${\beta}$-cells, hamster pancreatic cells. The concentrations of ceramide and dihydroceramide were 18.0 ${\pm}$ 12.0 and 0.025 ${\pm}$ 0.018 nmol/mg protein, respectively, in HIT-T15 cells. However, the concentrations of ceramide and dihydroceramide in the bacterial culture were 2.0 ${\pm}$ 1.2 and 10.6 ${\pm}$ 5.5 nmol/mg protein, respectively. $FB_1$ decreased the level of ceramide from 18.0 to 3.8 nmol/mg protein in HIT-T15 ${\beta}$-cells. However, dihydroceramide content in $FB_1$-treated HIT-T15 cells was slightly decreased compared with the control culture. When S. chungbukensis was treated with either $FB_1$ or desipramine, dihydroceramide level was increased by 5- and 4-fold, respectively, compared with the control bacteria. These results indicate that $FB_1$ and desipramine may act as an activator in bacterial sphingolipid biosynthetic pathway, and bacterial sphingolipid metabolism pathway appears to be different from the pathway of mammalian cells.

• Archives of Pharmacal Research
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• 제24권2호
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• pp.144-149
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• 2001

N-acetylsphingosine (C2-ceramide) is a synthetic water-soluble ceramide mimicking the activity of natural ceramides. By fixing chiral conformation on carbon numbers 2 and 3 in the ceramide structure, four chiral C2-ceramides naming d-erythro-, I-erythro-, d-threo-and 1-three C2-ceramide were synthesized. We have investigated the chiral effects of these C2-ceramides on the sphingolipid metabolism, particularly on both the sphingolipid bio- synthetic pathway and on the degradation pathway. In both HL-60 and U937 cells, the chiral C2-ceramide ($10{\mu}\textrm{m}$) showed sphingosine accumulation monitored fluoromatrically by a high performance liquid chromatographic separation of the sphingoid bases. Most importantly, in HL-60 cells, l-erythro C2-ceramide induced a 50 fold increase in sphingosine as compared to the control, while l-threo C2-ceramide exhibited a minimal 7-fold in-crease. In contrast, sphinganine, another sphingoid base, showed less accumulation by any chiral C2-ceramide tested under the same conditions. These results suggested that chiral C2-ceramide primarilyacts on the sphingolipid degradation pathway rather than on the sphingolipid biosynthetic route. The strong $C_0/G_1$ phase arrest in the cell cycle by treatment of I-erythro C2-ceramide indicates that the blockade of the sphingolipid degradation pathway might be concomitantly involved in the dysfunction of the cell cycle. On the other hand, the fact that all chiral C2-ceramides tested failed to inhibit the activity of sphingosine kinase acting on the removal of sphingosine by producing sphingosine-1 -phosphate demonstrates that chiral C2- ceramides may increase sphingosine by activating various ceramidases by which natural ceramides are divided into sphingosine and free fatty acids. However, the precise steps involved in this interaction are still unknown.

• Biomolecules & Therapeutics
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• 제20권5호
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• pp.470-476
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• 2012

Resveratrol, a chemopreventive agent, is rapidly metabolized in the intestine and liver via glucuronidation. Thus, the pharmacokinetics of resveratrol limits its efficacy. To improve efficacy, the activity of resveratrol was investigated in the context of sphingolipid metabolism in human gastric cancer cells. Diverse sphingolipid metabolites, including dihydroceramides (DHCer), were tested for their ability to induce resveratrol cytotoxicity. Exposure to resveratrol ($100{\mu}M$) for 24 hr induced cell death and cell cycle arrest in gastric cancer cells. Exposure to the combination of resveratrol and dimethylsphingosine (DMS) increased cytotoxicity, demonstrating that sphingolipid metabolites intensify resveratrol activity. Specifically, DHCer accumulated in a resveratrol concentration-dependent manner in SNU-1 and HT-29 cells, but not in SNU-668 cells. LC-MS/MS analysis showed that specific DHCer species containing C24:0, C16:0, C24:1, and C22:0 fatty acids chain were increased by up to 30-fold by resveratrol, indicating that resveratrol may partially inhibit DHCer desaturase. Indeed, resveratrol mildly inhibited DHCer desaturase activity compared to the specific inhibitor GT-11 or to retinamide (4-HPR); however, in SNU-1 cells resveratrol alone exhibited a typical cell cycle arrest pattern, which GT-11 did not alter, indicating that inhibition of DHCer desaturase is not essential to the cytotoxicity induced by the combination of resveratrol and sphingolipid metabolites. Resveratrol-induced p53 expression strongly correlated with the enhancement of cytotoxicity observed upon combination of resveratrol with DMS or 4-HPR. Taken together, these results show that DHCer accumulation is a novel lipid biomarker of resveratrol-induced cytotoxicity in human gastric cancer cells.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.162.2-163
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• 2003

Fumonisins are specific inhibitors of ceramide synthase in sphingolipid metabolism. The objective of this study was to investigate whether the elevation of free sphingoid bases 1-phosphate (S1P) are related to the fumonisin exposure. Sprague Dawley rats were injected i.p. with 10mg/kg fumonisin B1 (FB1), and kidney, liver, heart, lung, brain and serum were collected for sphingolipid analysis. (omitted)

• Molecules and Cells
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• 제43권5호
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• pp.419-430
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• 2020

The liver is an important organ in the regulation of glucose and lipid metabolism. It is responsible for systemic energy homeostasis. When energy need exceeds the storage capacity in the liver, fatty acids are shunted into nonoxidative sphingolipid biosynthesis, which increases the level of cellular ceramides. Accumulation of ceramides alters substrate utilization from glucose to lipids, activates triglyceride storage, and results in the development of both insulin resistance and hepatosteatosis, increasing the likelihood of major metabolic diseases. Another sphingolipid metabolite, sphingosine 1-phosphate (S1P) is a bioactive signaling molecule that acts via S1P-specific G protein coupled receptors. It regulates many cellular and physiological events. Since an increase in plasma S1P is associated with obesity, it seems reasonable that recent studies have provided evidence that S1P is linked to lipid pathophysiology, including hepatosteatosis and fibrosis. Herein, we review recent findings on ceramides and S1P in obesity-mediated liver diseases and the therapeutic potential of these sphingolipid metabolites.