• Toxicological Research
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• 제24권2호
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• pp.129-135
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• 2008

The results of recent studies indicate that high levels of free fatty acids(FFAs) and adipokines may be the main causes of non-alcoholic liver disease; however, the molecular mechanism that links FFAs to lipotoxicity remains unclear. In the present study, we treated HepG2 cells with FFA(either palmitate or oleate) to investigate the mechanisms involved in lipotoxicity in the liver cells. We also treated cells with palmitate in the presence of a chemical chaperone, 4-phenylbutyric acid(PBA), to confirm the involvement of ER stress in lipotoxicity. Palmitate significantly induced cytotoxicity in dose- and time-dependent manners. Apoptosis was also significantly induced by palmitate as measured by caspase-3 activity and DAPI staining. Palmitate led to increased expressions of the spliced form of X-box-protein(Xbp)-1 mRNA and C/EBP homologous transcription factor(CHOP) protein, suggesting activation of the unfolded-protein response. PBA co-incubation significantly attenuated apoptosis induced by palmitate. The above data demonstrate that high levels of palmitate induce apoptosis via the mediation of ER stress in the liver cells and that chemical chaperones act to modulate ER stress and accompanying apoptosis.

• 대한화장품학회지
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• 제22권1호
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• pp.40-59
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• 1996

Retinol은 열과 빛에 쉽게 산화되기 때문에 그 유도체인 Retinyl Palmitate를 사용하고 있으나 이것 또한 안정성이 우려되어 많은 양을 사용하지 못하고 있다. 본 연구에서는 Retinyl Palmitate 5% 와 Tocopgeryl Acetate 10%를 함유한 W/O, W/S, O/W, MLV Type의 크림에서 열적 안정성 및 UV 안정성을 CHROMA METERS로 측정하였으며, $25^{\circ}C$, $45^{\circ}C$에서 RP의 함량을 HPLC로 정량 분석하였다. 또한 RP가 열, 빛 등에 의해서 어떤 물질로 변화하였는지를 측정하였으며, 변화된 물질의 독성에 대한 연구를 하였다. 각각의 크림 TYPE 마다 입자 SIZE를 측정했으며, DNA와 CHROMA METERS를 사용하여 CELLULAR RENEWAL을 측정하였다.

• Journal of Pharmaceutical Investigation
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• 제30권4호
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• pp.259-266
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• 2000

Vitamin A palmitate, an oily drug which has low chemical stability and is poorly absorbed in the intestine, was formulated into a novel powdered dosage form. This is designated as a redispersible dry emulsion by freeze-drying technique. Before preparing a dry emulsion, vitamin A palmitate oil in solid in water (O/S/W) emulsion with soybean oil and coconut oil using Aerosil 200 as an emulsion stabilizer and polyoxyethylene-polyoxypropylene-blockcopolymer (Pluronic F68) as a surfactant was prepared. The resultants of the stability tests indicated that vitamin A palmitate O/S/W emulsion was improved on increasing the oil content of the formulation. The resultant dry emulsion particles have a good stabilities and free flow properties and readily released the oily droplets to form stable emulsions on rehydration. The drug releasing property from the resultant dry emulsion particles was dependent on factors such as amount of oily carrier(soybean oil) and surfactant(Pluronic F68) formulated. Above 80% of vitamin A palmitate content was released from the dry emulsion for 1 hour. It was deduced that vitamin A palmitate dry emulsion was definitely suitable for oral administration, since small droplets of vitamine A palmitate from the dry emulsion may alter the drug absorption profile resulting in bioavailability enhancement.

• 대한한의학회지
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• 제32권1호
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• pp.109-120
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• 2011

Objectives: The aim of this investigation was to evaluate the efficacy of KHchunggan-tang aqueous extract on the experimental nonalcoholic fatty liver disease(NAFLD) induced by palmitate. Materials and Methods: To generate a cellular model of NAFLD, we used HepG2 cells, a human hepatoma cell line, treated with 0.5 mM palmitate. By this cellular model, effects of KHchunggan-tang aqueous extract were evaluated. Intracellular lipid accumulation, free radical formation, and apoptosis were detected by Nile red staining, 2',7'-dichloroflourescin diacetate(H2DCF-DA), and 4',6-diamidino-2-phenylindole(DAPI)/propidium iodide(PI) staining, respectively. Some proteins related with NAFLD were determined by western blot. Results: Typical pathological features of NAFLD occurred in the cellular model. Palmitate increased the levels of intracellular lipid vacuoles, decreased cell viability, and increased apoptosis. Palmitate increased free radical formation and lipid peroxidation, too. However, KHchunggan-tang aqueous extract reduced palmitate-induced pathologic features, i.e. steatosis, free radical formation, and apoptosis. In addition, KHchunggan-tang aqueous extract suppressed palmitate-activated c-Jun N-terminal kinase(JNK) signaling, and SP600125, a JNK inhibitor, significantly reversed the palmitate-induced pathologic changes as KHchunggan-tang aqueous extract. It means that the signaling pathway other than JNK can be involved in the KHchunggan-tang mediated cellular protection of palmitate-treated Hep G2 cells. Conclusions: These results suggest that KHchunggan-tang aqueous extract has hepatoprotective effects on NAFLD with combined properties in cellular steatosis, ROS production, and cytoprotection, and thus may have valuable clinical applications for treatment of this chronic liver disease.

• 대한화학회지
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• 제37권3호
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• pp.302-308
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• 1993

Calcium-palmitate의 단분자막을 압전수정결정 위에 Langmuir-Blodgett(LB) 기법으로 적층시켜 수정판의 진동수 변화로부터 LB막의 적층수를 평가할 수 있었다. 바탕용액에 Ca$^{2+}C$ 이온을 포함하는 palmitic acid(PA) 단분자막으로부터 이전 및 적층된 LB막 물질을 적외선 분광분석을 한 결과 1704 cm$^{-1}C$에서 갈라진 흡수띠가 나타나는 것으로 보아 calcium palmitate가 형성되었음을 알 수 있었다. 1580cm$^{-1}C$과 1540cm$^{-1}C$의 두 흡수띠는 각각 calcium carboxylate기의 비대칭 신축진동과 carboxylate가 수화되어 대칭강하된 것으로 확인되었다$^1$. 이사실은 X-선 회절분석에 의해서도 확인되었다. 23$^{\circ}C$ 물 속에서 LB막의 팽윤거동을 LB막이 적층된 수정진동판의 진동수 변화로부터 관측되었다. Calcium palitate LB막은 충분히 팽윤이 되었으나 hexadecanol LB막은 거의 팽윤이 되지 않았다. Calcium palmitate LB막 팽창량은 무게비로 건조 LB막의 47${\%}$였으며 calcium palmitate 단위 분자당 7개의 물분자가 결합되었다. Calcium palmitate 건조 LB막의 화학적 구조는 [CH$_3$(CH$_2$)$_{14}$COO]$_2$Ca${\cdot}$XH$_2$O이고 수화수는 1 H$_2$O였다.

• 대한수의학회지
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• 제44권2호
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• pp.185-193
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• 2004

The effects of membrane lipid peroxidation and retinyl palmitate on rat liver microsomal functions were investigated in vitro. Rat liver homogenates exposed to oxygen tension for 0, 3, 6, 9 or12 hours and lipid peroxidation levels were evaluated by the measurements of fluorescence intensity, malondialdehyde (MDA) and retinyl palmitate. The fluorescence intensity of homogenates and microsomes were elevated and retinyl palmitate concentrations were decreased. But the concentration of MDA was not affected to exposure time. Therefore, fluorescence intensity and retinyl palmitate concentration were used to analyze the correlation between lipid peroxidation and microsomal functions. To investigate the liver microsomal functions, the microsome was isolated from rat liver homogenates exposed to oxygen. The concentration of cytochrome P450 and the activity of NADPH-cytochrome P450 reductase in liver microsomes were gradually decreased with increasing the exposure time. The correlation between fluorescence intensity of microsomes showed a very high inverse correlation of -0.97 and -0.93, respectively. The decrease of cytochrome P450 concentration was due to the regeneration of cytochrome P450 to cytochrome P420. Also, the activities of cytochrome P450-dependent aminopyrine demethylase and benzpyrene hydroxylase of liver microsomes were gradually decreased with increasing the exposure time. The correlation with fluorescence intensity of microsome showed a high inverse correlation of -0.97 and -0.91, respectively. The retinyl palmitate concentrations of rat liver homogenates were decreased with increasing the exposure time. The decrease of retinyl palmitate concentration was followed by a low concentration of cytochrome P450 and activity of NADPH-cytochrome P450 reductase. The correlation indicated high direct correlation of 0.92 and 0.93, respectively. The decrease of retinyl palmitate concentration was also accompanied by the reduction of aminopyrine demethylase and benzpyrene hydroxylase activities. The correlation was analyzed a high direct correlation of 0.90 and 0.85, respectively. In conclusion, these studies have shown that the membrane lipid peroxidation of rat liver microsome proportionally decreased microsomal enzyme activities in vitro experiments.

• 한국응용과학기술학회지
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• 제25권1호
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• pp.48-51
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• 2008

Dipalmitoyl phosphatidyl choline and p-nitrophenyl palmitate were directly sonicated in acidic water for 6 minutes to give clear stock solutions. The catalytic hydrolysis of p-nitrophenyl palmitate was studied at $30-50^{\circ}C$ in the presence of unilamellar vesicle and mixture of unilamellar and multilamellar aggregates. The difference of reaction rate between unilamellar and multilamellar was observed. The rate of unilamellar reaction compared to the rate of mixture reaction showed more catalytic effect. The phase transition temperature of vesicle was measured at $37-44^{\circ}C$.

• 한국동물학회지
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• 제36권1호
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• pp.84-96
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• 1993

한국산 도롱뇽(Hynobius leechii) 유생의 다리 발생 과정을 관찰하고 잠재적 돌연변이 유발물질인 제-methyl-N'-nitro-N-nitrosoguanidine(MNNG)과 잠재적 기형 유발물질인 retinol palmitate가 다리 발생에 미치는 영향을 알아보았다. 정상적인 개체에서 됫다리의 발생 단계는 외부와 내부의 형태적 특징을 기준으로 하여 7단계로 나누어 볼 수 있었으며 전연골세포의 밀집에 따른 골격형성은 다리 발생아의 근위부에서 시작하여 원위부로 진행됨을 확인할 수 있었다. 도롱뇽 유생을 MNNG(10 rpm)나 retinol palmitate(37.5 lpm)로 처리한 경우, 공통적으로 다리 원위부의 골격 형성이 억제되었으며, 특히 이러한 골격 형성 억제 현상은 처리시기가 이를수록 보다 심하게 나타났다. 이러한 결과는 발생을 저해하는 물질에 대한 미분화 상태의 세포들의 반응성이 발생과정 중 특정 단계에 국한됨을 시사하는 것으로 해석된다.

• BMB Reports
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• 제42권6호
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• pp.367-372
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• 2009

In this study, we showed that WAX9D, a nonspecific lipid-transfer protein found in broccoli, binds palmitate (C16) and stearate (C18) with dissociation constants of 0.56 ${\mu}M$ and 0.52 ${\mu}M$, respectively. WAX9D was fused to thioredoxin protein by genetic manipulation to enhance its solubility. The data revealed strong interaction of Trx-WAX9D with palmitate and stearate. The dissociation constants of Trx-WAX9D for palmitate and stearate were 1.1 ${\mu}M$ and 6.4 ${\mu}M$, respectively. The calculated number of binding sites for palmitate and stearate was 2.5 to 2.7, indicating that Trx-WAX9D can bind three molecules of fatty acids. Additionally, Trx-WAX9D was shown to inhibit the apoptotic effect of palmitate in endothelial cells. Our data using Trx-WAX9D provide insight into the broad spectrum of its biological applications with specific palmitate binding.

• 생명과학회지
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• 제29권9호
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• pp.964-971
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• 2019

간의 지질 축적과 인슐린 저항성은 비알콜성 지방간 환자에게서 증가한다. Piperine은 후추(Piper nigrum)와 필발(인도산 후추, P. longum)의 주요 성분으로 항암, 항비만, 항 당뇨병, 항염증 및 항산화 등의 생리활성이 보고되었다. 그러나 piperine의 인간 간세포 HepG2 세포에서 지질 축적과 인슐린 저항성의 억제제로서의 연구는 보고된 바가 없다. 본 연구의 목적은 지질 축적 및 인슐린 저항성에 대한 piperine의 효과를 palmitate처리된 HepG2 세포에서 잠재적인 분자 기전을 밝히는 것이다. 그 결과 piperine처리군은 지질 함량을 감소시켰고, 지방 형성 표적 유전자인 SREBP-1c와 FAS의 발현을 억제함으로써 palmitate처리된 세포내 지질 축적을 감소시켰다. 게다가 piperine처리군은 지방산 산화에 관련된 CPT-1과 인산화된 ACC 및 인산화된 IRS-1 (Tyr632)와 Akt의 레벨을 증가시켰다. 또한, piperine처리군은 인산화된 IRS-1 (Ser307)의 레벨을 감소시켰다. 결론적으로 palmitate처리된 HepG2 세포에서 piperine은 SREBP-1와 FAS발현의 감소 및 CPT-1과 ACC 인산화의 증가 및 인산화된 IRS-1(Try632)와 Akt 신호전달 경로를 조절함으로써 지질 축적 및 인슐린 저항성을 개선함을 확인하였다. 따라서 piperine의 지질 축적 및 인슐린 저항성을 예방하는 약물로써 가능성이 제시되었다.