• Archives of Pharmacal Research
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• 제27권7호
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• pp.742-750
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• 2004

This paper for the first time reports the isolation of 5 compounds from Phellinus linteus. A sphingolipid (1) and two tyrosinase inhibitory compounds (2, 3) along with two carboxylic acids (4, 5), were isolated from the fruiting body of Phellinus linteus (Berk ＆ Curt) Aoshima. The structure of compound 1 was identified as 1-O-$\beta$-D-glucopyranosyl-(2S, 3R, 4E, 8E)-2-[(2R)-2-hydroxyhexadecanoylamino]-9-methyl-4,8-octadecadiene-1,3-diol, known as cerebroside B, based on spectroscopic methods such as 1D and 2D NMR as well as by acid hydrolysis. Compounds 2-5 were identified as protocatechualdehyde (2), 5-hydroxymethyl-2-furaldehyde (HMF) (3), succinic acid (4), and fumaric acid (5) based on the spectroscopic evidence. Compounds 2 and 3 inhibited the oxidation of L-tyrosine catalyzed by mushroom tyrosinase with an $IC_{50}$ of 0.40 and 90.8 $\mu\textrm{g}$/mL, respectively. The inhibitory kinetics, which were analyzed by the Lineweaver-Burk plots, were found to be competitive and noncompetitive inhibitors with a $K_{j}$ of 1.1 $\mu\textrm{m}$ and 1.4 mM, respectively.

• Biomolecules & Therapeutics
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• 제31권2호
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• pp.183-192
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• 2023

p38 MAPK has been implicated in the pathogenesis of asthma as well as pro-allergic Th2 cytokines, orosomucoid-like protein isoform 3 (ORMDL3), regulation of sphingolipid biosynthesis, and regulatory T cell-derived IL-35. To elucidate the role of p38 MAPK in the pathogenesis of asthma, we examined the effect of NJK14047, an inhibitor of p38 MAPK, against ovalbumin (OVA)-induced allergic asthma; we administrated NJK14047 before OVA sensitization or challenge in BALB/c mice. As ORMDL3 regulation of sphingolipid biosynthesis has been implicated in childhood asthma, ORMDL3 expression and sphingolipids contents were also analyzed. NJK14047 inhibited antigen-induced degranulation of RBL-2H3 mast cells. NJK14047 administration both before OVA sensitization and challenge strongly inhibited the increase in eosinophil and lymphocyte counts in the bronchoalveolar lavage fluid. In addition, NJK14047 administration inhibited the increase in the levels of Th2 cytokines. Moreover, NJK14047 reduced the inflammatory score and the number of periodic acid-Schiff-stained cells in the lungs. Further, OVA-induced increase in the levels of C16:0 and C24:1 ceramides was not altered by NJK14047. These results suggest that p38 MAPK plays crucial roles in activation of dendritic and mast cells during sensitization and challenge periods, but not in ORMDL3 and sphingolipid biosynthesis.

• 운동영양학회지
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• 제23권2호
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• pp.1-6
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• 2019

[Purpose] Strenuous exercise often induces skeletal muscle damage, which results in impaired performance. Sphingolipid metabolism contributes to various cellular processes, including apoptosis, stress response, and inflammation. However, the relationship between exercise-induced muscle damage and ceramide (a key component of sphingolipid metabolism), is rarely studied. The present study aimed to explore the regulatory role of sphingolipid metabolism in exercise-induced muscle damage. [Methods] Mice were subjected to strenuous exercise by treadmill running with gradual increase in intensity. The blood and gastrocnemius muscles (white and red portion) were collected immediately after and 24 h post exercise. For 3 days, imipramine was intraperitoneally injected 1 h prior to treadmill running. [Results] Interleukin 6 (IL-6) and serum creatine kinase (CK) levels were enhanced immediately after and 24 h post exercise (relative to those of resting), respectively. Acidic sphingomyelinase (A-SMase) protein expression in gastrocnemius muscles was significantly augmented by exercise, unlike, serine palmitoyltransferase-1 (SPT-1) and neutral sphingomyelinase (N-SMase) expressions. Furthermore, imipramine (a selective A-SMase inhibitor) treatment reduced the exercise-induced CK and IL-6 elevations, along with a decrease in cleaved caspase-3 (Cas-3) of gastrocnemius muscles. [Conclusion] We found the crucial role of A-SMase in exercise-induced muscle damage.

• 생명과학회지
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• 제9권2호
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• pp.160-168
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• 1999

Butyrate는 탄소사슬이 짧은 지방산 중 하나로 소화되지 않은 식이성 섬유의 혐기적 발효결과 포유동물의 위장관내에 millimolar 농도로 유지되며 대장의 상피세포에서 흡수되어 energy원으로 사용된다. 70%정도 confluent하게 자란 사람의 대장암세포주인 HT29 cell에 5mM sodium butyrate를 시간별로 처리하고 세포의 생존율, 암세포의 분화정도의 biomarker로 알려진 alkaline phosphatase 및 PLC-rl의 발현정도를 측정하였으며 sphingolipid의 생합성 및 ceramidase 활성도 측정하였다. Sodium butyrate 처리는 성장중인 HT29 cell의 부착을 저해하여 처리 1일째부터 세포수가 감소하였고 형질막 효소인 alkaline phosphatase의 발현을 증가시켰으며 PLC-${\gamma}$의 발현을 감소시켰다. 또한, 복합 sphingolipid들의 생합성을 측정한 결과, 세포성장의 저해와 함께 sphingomyelin은 2일째부터 감소하였으며, galactosyl ceramide는 1일째부터 급속히 감소하였다. 그러나 ceramide의 경우, 1일째는 처리하기 전보다 680dpm/mg protein정도 증가하였으며 2일째에는 다시 급속히 감소하였다. 또한 butyrate처리에 의하여 HT29 cell의 acid ceramidase와 neutral ceramidase활성이 저해됨을 관찰하였는데 그 결과 ceramide함량이 초기에 증가된 것으로 생각된다. 본 실험결과들로부터 HT29 cell의 sodium butyrate처리는 세포분화 또는 세포성장저해를 가져오는데 이와 함께 초기의 ceramide함량 및 alkaline phosphatase활성의 증가와 galactosylceramide함량 및 LC-rl 발현의 감소현상이 동반됨을 알 수 있다.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2000년도 추계학술발표대회 및 bio-venture fair
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• pp.725-728
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• 2000

The effects of agitation rate and agitation time on the synthesis of sphingosome were studied. As increase in the agitation rates 4,000, 6,000, 8,000, 10,000 and 12,000 rpm the viscosity of sphingosome were decreased. The most sufficient agitation rate was 8,000rpm for which micell viscosity and stability. The effect of agitation time on the sphingosome viscosity and stability was investigated by changing the agitation times 2, 4, 6, 8 and 10 minute at 8,000rpm. 4 minute was the most sufficient for the viscosity and stability. The sphingolipid activity of cutaneous wound healing in impaired mice was examined. As a result, we could prove that phytosphingosine-HCl medically worked on wound healing well. For the phytosphingosine-HCl, it was found that the experimentally determined medical action more effective than that of tetra-acetylphytosphingosine.

• BMB Reports
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• 제53권1호
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• pp.28-34
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• 2020

Sphingolipids are ubiquitous building blocks of eukaryotic cell membranes that function as signaling molecules for regulating a diverse range of cellular processes, including cell proliferation, growth, survival, immune-cell trafficking, vascular and epithelial integrity, and inflammation. Recently, several studies have highlighted the pivotal role of sphingolipids in neuroinflammatory regulation. Sphingolipids have multiple functions, including induction of the expression of various inflammatory mediators and regulation of neuroinflammation by directly effecting the cells of the central nervous system. Accumulating evidence points to sphingolipid engagement in neuroinflammatory disorders, including Alzheimer's and Parkinson's diseases. Abnormal sphingolipid alterations, which involves an increase in ceramide and a decrease in sphingosine kinase, are observed during neuroinflammatory disease. These trends are observed early during disease development, and thus highlight the potential of sphingolipids as a new therapeutic and diagnostic target for neuroinflammatory diseases.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.69.1-69.1
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• 2003

Fumonisins are a family of mycotoxins produced from Fusarium verticillioides. Most of fumonisin B1 (FB1) toxicities can be explained by its ability to alter sphingolipid metabolism by inhibiting ceramide synthase. At least, the elevation in dihydrosphingosine (DHS) mediates the earliest toxicity of FB1. Some tissues such as kidney and liver, may be most affected by FB1 because they shows high rates of de novo sphingolipid synthesis. Recent review on FB1 toxicity by A.H. Merrill Jr. et al. suggested the possible role of dihydrosphingosine 1-phosphate (dihydroS1P), which sometimes elevated in cell- or tissue specific manners. (omitted)

• 한국미생물학회:학술대회논문집
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• 한국미생물학회 1997년도 제37회 춘계학술발표대회
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• pp.66.1-66.1
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• 1997

• Toxicological Research
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• 제27권3호
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• pp.185-190
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• 2011

Di-(2-ethylhexyl)-phthalate (DEHP), the most widely utilized industrial plastizer and a ubiquitous environmental contaminant, can act on peroxisome proliferators-activated nuclear hormone receptor family (PPAR) isoforms. To understand the contribution of sphingolipid metabolism to DEHP-induced hepatotoxicity, effect of DEHP exposure on activities of sphingolipid metabolic enzymes in rat liver was investigated. DEHP (250, 500 or 750 mg/kg) was administered to the rats through oral gavage daily for 28 days. The activities of acidic and alkaline ceramidases were slightly increased in 250 mg/kg DEHP-administered rat livers and significantly elevated in 500 mg/kg DEHP-administered ones, although the level of 750 mg/kg DEHP-administered ones was not increased. Neutral ceramidase, acidic and neutral sphingomyelinases, sphingomyeline synthase and ceramide syhthase were not changed at all by DEHP exposure. Therefore, acidic and alkaline ceramidases might play important roles in DEHP-induced hepatotoxicity.

• 약학회지
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• 제41권6호
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• pp.789-796
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• 1997

The purpose of this study was to determine the effect of sulfinpyrazone on fumonisin $B_1$-induced elevation of free sphingoid bases in LLC-$PK_1$ cells. Fumonis ins are a family of mycotoxins produced by the fungi Fusarium moniliforme which is common contaminant in corn. Fumonisins are also potent inhibiors of sphingosine and sphinganine N-acyltransferases (ceramide synthases), key enzymes in sphingolipid metabolism resulting in the elevation of free sphinganine. The cytosolic concentration of fumonisin B1 was known to be closely proportional to the elevation of free sphinganine in LLC-PK1 cells [Yoo, H.-S., Norred, W.P., Wang, E., Merrill, A.H., Jr., and Riley, R.T. (1992) Toxicol. Appl.Pharmacol. 114. 9-15]. Sulfinpyrazone, an anion transport inhibitor, reduced the elevated level of free sphinganine resulting from fumonisin B1 inhibition of de novo sphingolipid biosynthesis. Fumonisin B1 at a concentration of 20${\mu}$M showed approximately 120pmol/$10^6$ cells relative to 3-10pmol/$10^6$ cells in control cultures, and sulfinpyrazone at a concentration of 200${\mu}$M partially reversed the increased level of free sphinganine induced by fumonisin $B_1$ down to normal level after exposure to fumonisin $B_1$ for 8 to 24hr. However, the reduced effect of sulfinpyrazone on the fumonisin $B_1$-induced elevation of intracellular sphinganine was not shown after 24hr. Fumonisin $B_1$ exposure to LLC-PK1 cells for 36 and 48hr showed approximately 74 and 80pmol per $10^6$ cells relative to 82 and 76pmol,respectively, in fumonisin $B_1$ plus sulfinpyrazone-treated cultures. Sulfinpyrazone-induced less elevation of free sphinganine in confluent cells after exposure to fumonisin $B_1$ suggested that either sulfinpyrazone may block the availability of fumonisin $B_1$ to cells or act on the fumonisin $B_1$ interaction with ceramide synthase.