• BMB Reports
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• 제32권1호
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• pp.6-11
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• 1999

To understand the function of phospholipids and their fatty acid composition on the morphological changes in the amp 1-4 mutant of Arabidopsis, the mutant was compared to the wild-type Arabidopsis by TLC, HPTLC, phosphorous assay, HPLC, and GC. In the mutant, phosphatidylethanolamine (PE) was increased 5-fold and phosphatidylglycerol (PG) was decreased 1.2-fold (nmol phosphorous/g tissue). Inositol phospholipids showed a generally increased trend ranging from 1.4-to 3.0-fold (nmol inositol/g tissue). When fatty acid composition of the mutant was compared to the wild-type, linoleic (18:2) and linolenic (18:3) acids of phosphatidylcholine (PC) and PG were decreased but palmitoleic acid (16:1) and oleic acid (18:1) of PC was increased 2.5- and 2.1-fold (mol%), respectively. In galactolipids, myristic acid (14:0) of monogalactosyl-diacylglycerol (MGDG) were increased 5.8-fold (mol%). Among the inositol phospholipids, lysophosphatidylinositol (L-PI) and phosphatidylinositol 4,5-bisphosphate ($PIP_2$) showed 4-and 1.9-fold (mol%) increase of 16:1, respectively. These results suggest that the increase of PE, the decrease of PG, the increase of inositol phospholipids, and the altered fatty acid composition are related to the phenotypic changes affecting the morphological features, and might cause different physiological changes in the amp 1-4 mutant compared to wild-type Arabidopsis.

• Natural Product Sciences
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• 제23권1호
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• pp.35-39
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• 2017

D-chiro-inositol (DCI) is a secondary messenger in insulin signal transduction. It is produced in vivo from myo-inositol via action of epimerase. In this study, we evaluated antitumor activity of DCI against human breast cancer both in vitro and in vivo. In order to determine the inhibitory effects of DCI on growth of human breast cancer cells (MDA-MB-231), two different assessment methods were implemented: MTT assay and mouse xenograft assay. MTT assay demonstrated downturn in cell proliferation by DCI treatment (1, 5, 10, 20 and 40 mM) groups by 18.3% (p < 0.05), 17.2% (p < 0.05), 17.5% (p < 0.05), 18.4% (p < 0.05), and 24.9% (p < 0.01), respectively. Also, inhibition of tumor growth was investigated in mouse xenograft model. DCI was administered orally at the dose of 500 mg/kg and 1000 mg/kg body weight to treat nude mouse for 45 consecutive days. On the 45th day, tumor growth of DCI (500 mg/kg and 1000 mg/kg) groups was suppressed by 22.1% and 67.6% as mean tumor volumes were $9313.8{\pm}474.1mm^3$ and $3879.1{\pm}1044.1mm^3$, respectively. Furthermore, breast cancer stem cell (CSC) phenotype ($CD44^+/C24^-$) was measured using flow cytometry. On the 46th day, CSC ratios of DCI (500 mg/kg) and co-treatment with doxorubicin (4 mg/kg) and DCI (500 mg/kg) group decreased by 24.7% and 53.9% (p < 0.01), respectively. Finally, from tumor recurrence assay, delay of 5 days in the co-treatment group compared to doxorubicin (4 mg/kg) alone group was observed. Based on these findings, we propose that DCI holds potential as an anti-cancer drug for treatment of breast cancer.

• Molecules and Cells
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• 제43권3호
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• pp.222-227
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• 2020

Inositol polyphosphate multikinase (IPMK) is required for the biosynthesis of inositol phosphates (IPs) through the phosphorylation of multiple IP metabolites such as IP3 and IP4. The biological significance of IPMK's catalytic actions to regulate cellular signaling events such as growth and metabolism has been studied extensively. However, pharmacological reagents that inhibit IPMK have not yet been identified. We employed a structure-based virtual screening of publicly available U.S. Food and Drug Administration-approved drugs and chemicals that identified the antidepressant, vilazodone, as an IPMK inhibitor. Docking simulations and pharmacophore analyses showed that vilazodone has a higher affinity for the ATP-binding catalytic region of IPMK than ATP and we validated that vilazodone inhibits IPMK's IP kinase activities in vitro. The incubation of vilazodone with NIH3T3-L1 fibroblasts reduced cellular levels of IP5 and other highly phosphorylated IPs without influencing IP4 levels. We further found decreased Akt phosphorylation in vilazodone-treated HCT116 cancer cells. These data clearly indicate selective cellular actions of vilazodone against IPMK-dependent catalytic steps in IP metabolism and Akt activation. Collectively, our data demonstrate vilazodone as a method to inhibit cellular IPMK, providing a valuable pharmacological agent to study and target the biological and pathological processes governed by IPMK.

• KSBB Journal
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• 제19권6호
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• pp.462-466
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• 2004

S. coelicolor A3(2)로부터 항산화 저분자 thiol분자인 MSH를 HPLC 및 monobromobimane 형광 검출 방법으로 분리${\cdot}$정제하여 그 존재를 확인하였다. 표준물질인 MSH-bimane과 동일하게 용출되는 MSH 분획을 확인하였으며 여러 thiol 분획 중 MSH 분획이 가장 많은 것으로 보아 MSH가 S. coelicolor의 주된 thiol 화합물로 판단되었다. MSH 생합성에 관여하는 효소 중 I-1-Pase의 유전자의 기능을 알아보기 위하여 이 유전자를 방선균에서 분리한 후 대장균에 클로닝하여 과도발현시켰다. 발현된 I-1-Pase를 Ni-NTA column을 사용하여 정제하였다. 정제된 I-1-Pase는 soluble protein으로 281개 아미노산으로 구성되어 있으며 분자량은 32 kDa이었다. 인간 및 대장균의 I-1-Pase와 각각 24와 $25\%$의 sequence homology를 보였으며, 기존의 I-1-Pase가 가지고 있는 공통의 I-1-Pase motif A와 motif B를 S. coelicolor A3(2)도 가지고 있는 것으로 확인되었다.

• 한국산학기술학회논문지
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• 제12권7호
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• pp.3310-3316
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• 2011

Hematoxylin은 한국의 남부지방에서 당뇨합병증을 치료하기 위하여 사용해오던 민간약제인 Hematoxylon campechianum의 주성분이다. 본 논문에서는 hematoxylin의 혈당저하 메커니즘을 연구하기 위하여 3개 군의 흰쥐-정상군, 당뇨군, hematoxylin 처치군-에서 분리한 대퇴신경을 대상으로 2-deoxyglucose 수송능과 인지질 대사능을 조사였다. 실험결과 hematoxylin은 당뇨군에서 혈당치를 현저하게 감소시키는 것으로 나타났다. 또한 무게단위의 기준으로 당뇨군의 신경조직의 경우, 총 인지질의 양은 20% 감소하였으나 상대적으로 phosphatidylinositide의 감소는 작은 것으로 나타났다. 이 경우, hematoxylin을 처치하면 2-[3H] myo-inositol이 총 phosphoinositids로 대사되는 비율이 증가하는 것으로 밝혀졌다. 이러한 효과는 낮은 농도의 hematoxylin 처치군보다 높은 농도의 처치군에서 훨씬 큰 것으로 나타났다. 이상의 실험결과는 hematoxylin의 당뇨개선 메커니즘이 myo-inositol 대사를 증가시킴으로써 체내 당 수송과 인지질 대사를 정상화시킨다는 점을 제시하고 있다. 따라서 본 연구결과를 토대로 저자들은 hematoxylin은 향후 당뇨 치료제로서 후보 물질이 될 수 있음을 제시하고자 한다.

• 한국잠사곤충학회지
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• 제35권1호
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• pp.7-10
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• 1993

제한된 기간내에 접목 노력의 집중화에 따른 일손 부족 및 묘질의 저하를 막기 위하여 접목시기를 앞당겨 접목을 실시하고, 접목묘를 건조 톱밥 중량 대비 1.5배와 2.0배의 수분율을 조절한 톱밥에 저장하였으며, 접목 당일 채취한 것과 접목 10일전 채취, 15$^{\circ}C$ 항온기에 보존한 수목을 써서 접목을 하고, 접목당일 접눈의 유기 및 무기성분과 활착률과등을 분석 조사하였다. 1. 접목묘 저장용 톱밥의 최적 수분율은 건조 톱밥 중량 대비 1.5배이었다. 2. 활착율일 가장 높았던 접목시기는 관행인 3월 27일구의 81.0%이었으며, 3월 3일 접목구는 74.4%, 2월 17일구는 75.5%로 관행구 대비 5.3~6.3%, 생육상태는 5.7~7.9cm 떨어졌으나 통계적인 유의차는 인정되지 않았다. 3. 접목 20일전 채취하여 항온조건에 보존한 것은 활착율이 현저히 감소하였다. 보존수목은 당일 채취한 수목에 비하여 수분, T-N, P2O5, CaO, inositol 등은 높았으나, glucose, fructose, sucrose, total carbohydrate 등은 낮았다. 4. 접목적기에 가까워짐에 따라 접눈중에 fructose는 증가하는 반면, inositol은 3월 초에 약간 증가하였다가 하순경에는 급격히 감소하는 것이 수목저장구와 크게 다른 점이었다.

• The Korean Journal of Physiology and Pharmacology
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• 제2권1호
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• pp.41-48
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• 1998

The present study was undertaken to characterize homocysteic acid (HCA)-and cysteic acid (CA)-mediated formation of inositol phosphates (InsP) in primary culture of rat cerebellar granule cells. HCA and CA stimulated InsP formation in a dose-dependent manner, which was prevented by the N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2-amino-5-phosphopentanoic acid (APV). CA-, but not HCA-, mediated InsP formation was in part prevented by the metabotropic glutamate receptor antagonist ?${\alpha}$-methyl-4-carboxyphenylglycine ($({\pm})$-MCPG). Both HCA- and CA-mediated increases in intracellular calcium concentration were completely blocked by APV, but were not altered by $({\pm})$-MCPG. CA-mediated InsP formation was in part prevented by removal of endogenous glutamate. In contrast, the glutamate transport blocker L-aspartic acid-${\beta}$-hydroxamate synergistically increased CA responses. These data indicate that in cerebellar granule cells HCA mediates InsP formation wholly by activating NMDA receptor. In contrast, CA stimulates InsP formation by activating both NMDA receptor and metabotropic glutamate receptor, and in part by releasing endogenous glutamate into extracellular milieu.

• Natural Product Sciences
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• 제22권3호
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• pp.168-174
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• 2016

Anti-melanogenic effects of amaranth (AT), one of the key source of squalene, were investigated in melanocytes. Amaranth seed powder was extracted with water and melan-a cells were treated with various concentrations of AT. By using HPLC, content of myo-inositol, one of potential active components, was measured in the crude extract of AT.AT reduced the melanin content in melan-a melanocytes and down-regulated melanogenic enzyme activity such as tyrosinase, TRP-1 and TRP-2. By regulating melanogenic enzyme activity, AT may be a potential natural source for whitening agent. Myo-inositol was detected in AT by HPLC and may be one of the active compounds from AT involved in the regulation of anti-melanogenesis. In this study, we demonstrated that AT has anti-melanogenesis properties. This new function of amaranth may be useful in the development of new skin-whitening products and its value as food.

• Bulletin of the Korean Chemical Society
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• 제31권12호
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• pp.3623-3631
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• 2010

We prepared several novel molecular transporters built on myo- and scyllo-inositol scaffolds with variations in the number of guanidine residues, linker chain lengths and patterns. Some of these transporters were found to localize in mitochondria, and the mitochondrial affinity seems to be substantially related to the scaffold stereochemistry.

• 약학회지
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• 제54권1호
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• pp.8-12
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• 2010

Inositol 1,4,5-trisphosphate ($IP_3$) receptor ($IP_3R$)-mediated signaling pathway is involved in many cellular processes including fertilization, apoptosis and neuronal function. Although cardiac myocytes express the $IP_3R$, its pathophysiological role has not been clearly understood because of limited selectivity of currently available pharmacological blockers. In the present study we constructed shRNA-expressing adenovirus to knock-down the type 2 $IP_3R$ ($IP_3R2$), a major subtype in cardiac ventricular myocytes, and demonstrated that the virus successfully eliminated the expression and localization of the $IP_3R2$. These results may provide a reliable tool for probing pathophysiological roles of the $IP_3R2$ in isolated intact cardiac myocytes.