• 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.

• Biomolecules & Therapeutics
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• 제18권3호
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• pp.262-270
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• 2010

CD95 receptor is a member of tumor necrosis factor receptor family that mediates apoptosis in many cell types when bound by CD95 ligand or cross-linked by agonistic anti-CD95 antibodies. To determine the role of neutral sphingomyelinase (nSMase) on CD95-mediatd apoptosis, human Jurkat T lymphocytes were exposed to recombinant human CD95 ligand. Treatment with CD95 ligand induced cell death in a concentration and time-dependent manner. CD95-induced cell death was suppressed by inhibitors of SMase such as AY9944 or desipramine. Transfection with human nSMase1 siRNA plasmid into CD95 ligand-treated cells significantly prevented CD95-mediated cell death. CD95-mediated elevation of intracellular ceramide level detected by FACS analysis with anti-ceramide antibody was also decreased by nSMase1 siRNA. Knock-down of nSMase1 expression also blocked cytochrome c release into cytosol and caspase-3 cleavage in CD95-treated cells. Taken together, these results suggest that nSMase1 may play an important role in CD95-mediated apoptotic cell death in Jurkat T cells.

• The Korean Journal of Physiology and Pharmacology
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• 제15권6호
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• pp.423-429
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• 2011

B13 analogues are being considered as therapeutic agents for cancer cells, since B13 is a ceramide analogue and inhibits ceramidase to promote apoptosis in cancer cells. B13 sulfonamides are assumed to have biological activity similar to B13, since they are made by bioisosterically substituting the carboxyl moiety of B13 with sulfone group. Twenty B13 sulfonamides were evaluated for their in vitro cytotoxicities against human colon cancer HT-29 and lung cancer A549 cell lines using MTT assays. Replacement of the amide group with a sulfonamide group increased cytotoxicity in both cancer cell lines. The sulfonamides with long alkyl chains exhibited activities two to three times more potent than that of B13 and compound (15) had the most potent activity with $IC_{50}$ values of 27 and $28.7{\mu}M$ for HT-29 and A549, respectively. The comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were used to carry out QSAR molecular modeling of these compounds. The predictive CoMSIA models for HT-29 and A549 gave cross-validated q2 values of 0.703 and 0.830, respectively. From graphical analysis of these models, we suppose that the stereochemistry of 1,3-propandiol is not important for activity and that introduction of a sulfonamide group and long alkyl chains into B13 can increase cytotoxicity.

• 대한화장품학회지
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• 제27권1호
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• pp.3-15
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• 2001

The bilayer forming ability of pseudo-ceramide PC104 in octanoic acid/water/n-octyl $\beta$-D-glucoside mixtures was investigated through the phase diagram. Because of its low solubility in water and of its crystallization, pseudoceramide PC104 was dissolved in octanoic acid, which is nontoxic additive for foods and cosmetics. The mixtures formed four different phases (L1, L2, LC and two phases). Depending on the concentration of PC104 in octanoic acid, the region of each phase was extended or contracted. On the contrary to the region of L2, regions of lamellar phase and L1 phase were expanded. The bilayer-forming ability of PC104 was explained on the basis of concentration of PC104 at interface and interaction between PC104 and octanoic acid. From FT-IR results, it was found that the interactions of PC104’s polar head group with octanoic acid increased as the amount of PC104 in octanoic acid increased. Also emulsion size and size distribution have been studied depending upon the emulsification path. droplets of emulsion prepared from lamellar phase were smaller and more homogeneous compared to those of emulsions formed from L2 phase.

• 분석과학
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• 제8권4호
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• pp.901-906
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• 1995

Studies on the chemical constituents from a Korean wild mushroom, Phellinus ribis, were carried out. A triterpenoid, two peroxysterols, and a chlorobenzene compound were isolated from the hexane soluble fraction of the methanol extract of dried fruiting bodies of the basidomycetes. Those compounds identifed were 3-hydroxy-20(29)-lupen-28-oic acid (betulinic acid), 5,8-epidioxyergosta-6,22-dien-3-ol(ergosterol peroxide), 5,8-epidioxyergosta-6,9(11),22-trien-3-ol (dehydroperoxyergosterol), and 1,2,4,5-tetrachloro-3,6-dimethoxybenzene. Structural studies were carried out on molecular species of a ceramide and cerebroside isolated from the chloroform soluble fraction of the methanol extract. For ceramide, the major component fatty acids were a-hydroxy fatty acid isomers of $C_{22:00}{\sim}C_{25:00};$ the predominant long-chain bases were trihydroxy sphinganine of $C_{17}{\sim}C_{18}$. The structure of a cerebroside containing mono-sugar was assumed that the long-chain base was $C_{19:2}$ sphingadienine; the major fatty acids were $C_{16}{\sim}C_{15}$ ${\alpha}$-hydroxy fatty acid isomers.

• The Korean Journal of Physiology and Pharmacology
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• 제17권3호
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• pp.237-243
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• 2013

B13 is a ceramide analogue and apoptosis inducer with potent cytotoxic activity. A series of arylpropyl sulfonamide analogues of B13 were evaluated for their cytotoxicity using MTT assays in prostate cancer PC-3 and leukemia HL-60 cell lines. Some compounds (4, 9, 13, 14, 15, and 20) showed stronger activities than B13 in both tumor cell lines, and compound (15) gave the most potent activity with $IC_{50}$ values of 29.2 and 20.7 ${\mu}M$, for PC-3and HL-60 cells, respectively. Three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis was performed to build highly reliable and predictive CoMSIA models with cross-validated $q^2$ values of 0.816 and 0.702, respectively. Our results suggest that long alkyl chains and a 1R, 2R configuration of the propyl group are important for the cytotoxic activities of arylpropyl sulfonamides. Moreover, the introduction of small hydrophobic groups in the phenyl ring and sulfonamide group could increase biological activity.

• Applied Biological Chemistry
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• 제50권1호
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• pp.72-76
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• 2007

대표적인 스핑고지질인 글리코실세라미드의 생리적 기능을 조사하기 위하여 쌀겨 추출물로부터 cerebroside를 분리하였다. 정제하지 않은 글리코실세라미드를 flash system 칼럼으로 분리한 후 ELSD를 검출기로 사용하여 순상 HPLC로 정제하였다. 클로로포름 : 메탄올 : 증류수(99:11:1, v/v/v)을 용출용매로 사용하여 주요 cerebroside를 얻을 수 있었고, MALDI/TOF-MS, FAB-MS, GC, 600MHz $^1$H-NMR로 구조를 분석하였다. 구성당은 글루코오스였고 cerebroside의 구성 지방산은 2-hydroxy-arachidic산이었다. 장쇄 염기는 sphinga-4,8-dienine이었다.

• Nutrition Research and Practice
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• 제18권5호
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• pp.602-616
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• 2024

BACKGROUND/OBJECTIVES: Inflammation and ferroptosis are implicated in various diseases and lipopolysaccharides (LPS) have been linked with these disorders. Recently, many edible insects, such as Gryllus bimaculatus, Protaetia brevitarsis larvae (PB) and Tenebrio molitor larvae, have been recommended as alternative foods because they contain lots of nutritional sources. In this study, we explored the potential of PB extract in preventing LPS-induced inflammation and ferroptosis in Hep3B cells. MATERIALS/METHODS: PB powder was extracted using 70% ethanol and applied to Hep3B cells. Co-treatment with LPS was conducted to induce ferroptosis and inflammation. The anti-inflammatory and anti-ferroptosis mechanisms of the PB extract were confirmed using Western blot, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction analysis. RESULTS: PB extract effectively prevented LPS-induced cell death and restored LPS-induced inflammatory cytokine production, NF-κB signaling, endoplasmic reticulum (ER) stress and ferroptosis. Interestingly, PB extract reduced LPS-induced ceramide increase and acid sphingomyelinase (ASMase) expression. The use of the ASMase inhibitor, desipramine, also demonstrated a reduction in these pathways, highlighting the pivotal role of ASMase in inflammation and ferroptosis. Treatment with each inhibitor revealed that ferroptosis causes ER stress and that NF-κB and MAP kinase pathways are involved in inflammation. CONCLUSION: PB emerges as a potential functional food with inhibitory effects on LPS-induced inflammation and ferroptosis, making it a promising candidate for nutritional interventions.

• 한국식품영양과학회지
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• 제31권2호
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• pp.177-183
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• 2002

대두 및 대두발효식품인 청국장과 된장의 cerebroside 구성성분인 지방산, 당 및 장쇄 sphingoid base들을 GC-MS로 분석하였다. Cerebroside 산-가수분해물의 지방산들을 O-TMS methylester 유도체로 만들어 분석하였으며 대두 및 청국장의 경우 2-hydroxyhexadecanoic acid(16 : 0h)가 각각 52.2% 및 62.0%로 가장 많았고 2-hydroxydocosanoic acid(22 : 0h) 및 2-hydroxytetracosanoic acid(24 : 0h)도 15.0~17.6%이었다. 그러나 된장의 경우 16 : 0h는 10.2%로 많은 감소를 보인 반면 24 : 0h는 40.9%, 22 : 0h는 23.4% 었으며 23 : 0h, 25 : 0h 및 26 : 0h도 대두 및 청국장에 비하여 많았다. Cerebroside 산-가수분해물의 장쇄 sphingoid base들은 N-acetyl-O-TMS 유도체로 분석하였으며 대두 및 청국장에서 4- trans, 8-trans-sphingadienine (d18 : 2 $\Delta$$^{4trans, 8trans}$) 는 59.9% 및 44.5%이었으며 4-hydroxy-8-trans, cis-sphingening (t18 : 1$\Delta$$^{8trans or cis}$)는 20.9% 및 35.9% 이었고 된장 cerebroside 역시 dl8 : 2$\Delta$$^{4trans, 8trans}$가 가장 많았다. 그러나 phytosphingosine(t18 : 0) 및 sphingosine 이 성질체(d18 : 1)들은 거의 보이지 않았다. 또한 된장의 경우 오랜 기간 미생물들에 의하여 발효되었지만 Aspergillus 속들의 cerebroside가 가지는 것으로 알려진 2-hydroxyoxtadec-3-enoic acid(18 : 1h) 및 9-methyl-4,8-sphingadienine 등은 발견되지 않았다. 대두, 청국장 및 된장 cerebroside의 당유도체 mass spectrum 분석 결과 99%이상이 glucose 1번 탄소가 ceramide backbone에 결합된 monoglucocerebroside 인 것으로 나타났다.

• 대한화장품학회지
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• 제30권3호
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• pp.345-352
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• 2004

아토피 피부염을 설명하는 데는 두 가지 패러다임이 있는데, 첫 번째는 outside-inside paradigm이고 두 번째는 inside-ouside paradigm이다. Outside-inside paradigm에 의하면 아토피 피부염을 치료하기 위한 가장 좋은 방법은 피부 장벽 기능을 회복시키는 것이다. 장벽 기능은 각질층의 특징적인 구조에 의해 유지되는데, 각질층은 층상구조의 inter-cellular lipids와 corneocyte로 구성되어 있다. 아토피 피부염 환자, 층판상 어린선 환자의 각질층 내 층상구조는 hexagonal 구조가 많이 존재하고 있음을 보였으며, 이는 Ceramide 1 타입과 long chain fatty acid의 감소 때문이라고 보여진다. 이러한 이유에서 라멜라구조를 가지며 intercellular long periodicity phase 기능을 복원할 수 있는 보습제는 각질층의 intercellular lipid의 층상구조를 복원시킬 수 있을 것이다. 또한 세라마이드와 유사세라마이드를 함유한 보습제는 손상된 피부장벽, 피부질환, 아토피 피부염을 위한 유용한 치료제로 사용할 수 있다. Inside-outside paradigm에 따르면, 아토피 피부염 등이 보조 T cell, lg E, eosinophil 등을 포함한 면역반응과 관계되는데, 특히 Th1/Th2 imbalance의 복원이 아토피 피부염을 치료하는데 효과적일 것이다. 현재 여러 종류의 면역억제제가 소개되고 있지만, 이들은 고유 면역기능을 감소시킬 우려를 가지고 있다. 따라서, 세라마이드 대사산물인 SPC와 S1P는 면역조절 기능 및 상처치유의 기능을 가짐으로써 향후 관심이 집중될 것이다.