• 한국수산과학회지
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• 제36권5호
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• pp.442-448
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• 2003

Melanin concentrating hormone (MCH) regulating color change of fish skin was identified from brain cDNA library of Olive flounder (Paralichthys olivaceus) during the analysis of Expressed Sequence Tags (ESTs). Olive flounder MCH gene consisted of 598 nucleotides encoding 150 amino acids. Olive flounder MCH protein revealed to contain signal peptide of 19 amino acid residues, pro-MCH of 131 amino acids being processed to biologically active and mature form of hormone with 25 amino acid residues at the carboxyl terminus. A comparative structural analysis revealed that Olive flounder MCH precursor had low sequence identity with other fish species and mammalian counterparts, while the amino acid sequences of mature hormone had a relatively high identity and more conserved. RT-PCR analysis revealed that olive flounder MCH precersor gene was expressed spectically only in the brain and not in other tissues.

• Biomolecules & Therapeutics
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• 제18권2호
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• pp.152-158
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• 2010

Melanin concentrating hormone is a neuropeptide highly expressed in the brain that regulates several physiological functions mediated by receptors in the G-protein coupled receptor family, especially plays an important role in the complex regulation of energy balance and body weight mediated by the melanin concentrating hormone receptor subtype 1 (MCH1). Compelling pharmacological evidence implicating MCH1 signaling in the regulation of food intake and energy expenditure has generated a great deal of interest by pharmaceutical companies as MCH1 antagonists may have potential therapeutic benefit in the treatment of obesity and metabolic syndrome. Although fluorescence-based calcium mobilization assay platform has been one of the most widely accepted tools for receptor research and drug discovery, fluorescence interference and shallow assay window limit their application in high throughput screening and have led to a growing interest in alternative, luminescence-based technologies. Herein, a luminescence-based functional assay system for the MCH1 receptor was developed and validated with the mitochondrial targeted aequorin. Aequorin based functional assay system for MCH1 presented excellent Z' factor (0.8983) and high signal-to-noise ratio (141.9). The nonpeptide MCH1 receptor antagonist, SNAP 7941 and GSK 803430, exhibited $IC_{50}$ values of 0.62 ${\pm}$ 0.11 and 12.29 ${\pm}$ 2.31 nM with excellent correlation coefficient. These results suggest that the aequorin based assay system for MCH1 is a strong alternative to the traditional GPCR related tools such as radioligand binding experiments and fluorescence functional determinations for the compound screening and receptor research.

• 생명과학회지
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• 제28권3호
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• pp.284-292
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• 2018

멜라닌 농축 호르몬(melanin-concentrating hormone, MCH)은 17개의 아미노산으로 구성된 환형의 시상하부 펩티드로 색소 침착의 조절인자로서 연어에서 처음 분리되었다. 포유동물의 MCH는 19개의 아미노산으로 구성되어 있으며 섭식 및 에너지 항상성을 조절하는데 관여한다. 본 연구에서는 양식넙치의 다양한 조직에서 MCH 유전자의 발현 분포, 멜라닌 함유 세포의 집적, 포유동물 MCH 수용체와 양식넙치 MCH의 상호작용을 조사하였다. Real-time qPCR을 이용하여 뇌, 정소, 난소에서 MCH 유전자의 발현이 나타나는 것을 확인하였고, 수정 후 발달 단계에서도 MCH 유전자의 발현을 확인할 수 있었다. 합성된 연어 sMCH, 포유류 hMCH, 양식넙치 fMCH, dN-fMCH, dC-fMCH를 양식 넙치의 표피에 처리했을 때 다양한 농도에 따라 멜라닌 함유 세포의 집적이 다양하게 나타났다. 연어 sMCH, 포유류 hMCH에 비해 양식넙치 fMCH의 멜라닌 함유세포의 집적도가 36~99.85%로 비역가를 나타났으나 양식넙치 dN-fMCH, dC-fMCH를 처리한 경우 양식넙치 fMCH에 비해 높은 농도에서 집적이 나타나고 짧은 시간에 분산되었다. 또한, 인간 MCH 수용체와 쥐 MCH 수용체가 발현된 포유동물의 세포주에 양식넙치 fMCH를 처리하여 각 수용체와 결합하는 것을 확인하였다. 이러한 결과는 어류에서 발현되는 MCH가 포유동물의 MCH와 유사한 구조를 가지고 있어 MCH 수용체에 대한 새로운 리간드로서 제공될 수 있으며, 향후 어류의 MCH 수용체에 확대 적용할 수 있을 것이다.

• Bulletin of the Korean Chemical Society
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• 제33권7호
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• pp.2389-2392
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• 2012

• Bulletin of the Korean Chemical Society
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• 제28권7호
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• pp.1151-1155
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• 2007

In a previous study, a catalyst (A) was discovered for oxidative decarboxylation of melanin-concentrating hormone (MCH). To explain the catalytic action and to predict the structure of a new catalyst with improved activity, docking simulations were carried out for the complex formed between A and MCH. The simulations suggested that the three terminal groups of A form a hydrophobic pocket and that van der Waals interactions between the hydrophobic pocket and MCH play a role in stabilizing the MCH-A complex. Consequently, a new catalyst (B) was designed and synthesized in expectation of improved catalytic activity resulting from enhanced van der Waals interactions. The new catalyst, however, showed slightly lower catalytic activity. Lack of the accurate solution structure of MCH may be one of the factors associated with difficulties in prediction of improvement in catalytic activity by purely theoretical means. The results, however, revealed that variation of the acyl portion of the hydroxyproline portion may lead to improved catalysts.

• Bulletin of the Korean Chemical Society
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• 제34권8호
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• pp.2305-2310
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• 2013

A novel series of 2-heteroaryl substituted benzimidazole derivatives, containing the piperidinylphenyl acetamide group at the 1-position, were synthesized and evaluated as MCH-R1 antagonists. Extensive SAR investigation probing the effects of C-2 heteroaryl group led to the identification of 2-[2-(pyridin-3-yl)ethyl] analog 3o, which exhibits highly potent MCH-R1 binding activity with an $IC_{50}$ value of 1 nM. This substance 3o also has low hERG binding activity, good metabolic stability, and favorable pharmacokinetic properties.

• Natural Product Sciences
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• 제15권1호
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• pp.27-31
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• 2009

The present study was performed to investigate the binding affinity of the ethanol extract from the leaves of Morus alba (EMA) and some EMA related plant materials (EMA-D, EMA-DM) for melanin-concentrating hormone-1 receptor (MCH-1) and also to examine the antagonistic effect of them for the recombinant MCH-1 receptor expressed in CHO cells. EMA, dichloromethane fraction (EMA-D) and EMA-DM exhibited high affinity for mammalian MCH receptor in receptor binding assays ($IC_{50}$ value: 2.3, 1.6 and $1.0{\mu}g/ml$, respectively). Other plant materials (MMA-D, MMA-DM) obtained from methanol extracts from the leaves of Morus alba (MMA) also exhibited high affinity for mammalian MCH receptor, even though the $IC_{50}$ values of them were lower than those of EMA-D and EMA-DM. In Chinese hamster ovary (CHO) cells expressing human MCH-1, EMA-DM and EMA-D significantly inhibited MCH-induced intracellular $Ca^{2+}$ increase ($IC_{50}$ values: 16.5 and $22.7{\mu}g/ml$, respectively). These results clearly indicate that the ethanol extract from the leaves of Morus alba (EMA) and some EMA related plant materials (EMA-D, EMA-DM) are novel selective MCH-1 receptor antagonist, respectively.

• Bulletin of the Korean Chemical Society
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• 제34권12호
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• pp.3851-3854
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• 2013

• Fisheries and Aquatic Sciences
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• 제17권3호
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• pp.325-337
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• 2014

To assess the functional structure of prepro-melanin-concentrating hormone (pMCH), we isolated and cloned pMCH (of-pMCH) mRNA from the brain of the olive flounder, Paralichthys olivaceus, and compared its amino acid sequence with those from other animals. In addition, to examine whether activation of the brain of-pMCH gene is influenced by background color, density, and feeding, we compared pMCH mRNA activities against different background colors (bright and dark) and at different densities (100% PCA and 200% PCA). To examine whether the pMCH gene is related with malpigmentation of blind-side skin and appetite, we compared pMCH gene expression between ordinary and hypermelanic flounders, and between feeding and fasting flounders. The of-pMCH cDNA was 405 bp in the open reading frame [ORF] and encoded a protein of 135 amino acids; MCH was 51 bp in length and encoded a protein of 17 amino acids. An obvious single band of the expected size was obtained from the brain and pituitary by RT-PCR. In addition, of-pMCH gene activity was significantly higher in the bright background only at low density (< 100% PCA) making the ocular skin of fish whitening, and in ordinary fish. However, the gene activity was significantly decreased in dark background, at high density (>200% PCA), and in hypermelano fish. These results suggest that skin whitening camouflage of the flounder is induced by high MCH gene activity, and the density disturbs the function of background color in the physiological color change. Moreover, our data suggest that a low level of MCH gene activity may be related to malpigmentation of the blind-side skin. In feeding, although pMCH gene activity was significantly increased by feeding in the white background, the pMCH gene activity in the dark background was not influenced by feeding, indicating that the MCH gene activity increased by feeding can be offset by dark background color, or is unaffected by appetite. In conclusion, this study showed that MCH gene expression is related to ocular-skin whitening camouflage and blind-skin hypermelanosis, and is influenced by background color and density.