• 통합자연과학논문집
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• 제5권2호
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• pp.65-71
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• 2012

Neuropeptide Y (NPY), a 36-amino acid polypeptide, is a member of the pancreatic polypeptide family, which consists of NPY, peptide YY (PYY) and pancreatic polypeptide (PP). The neuropeptide Y (NPY) receptors called Y receptors belongs to G-protein coupled that are involved in a variety of physiological functions such as appetite regulation, circadian rhythm and anxiety. Five receptor subtypes have been cloned in mammals (Y1, Y2, Y4, Y5, and Y6) of which four are functional. In this short review, information about the functional NYP receptors was analyzed. Sequence analyses were done between these receptors to identify the relationships between them. Phylogram was generated between these receptors to identify the close homologue between these receptors. Our sequence analyses found that Y1 and Y4 receptors are close than the other receptors. Further structure based analysis could be useful to identify subtype selective antagonists and dual antagonists targeting Y1 and Y4 receptors.

• Molecules and Cells
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• 제37권4호
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• pp.295-301
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• 2014

SIFamide receptor (SIFR) is a Drosophila G protein-coupled receptor for the neuropeptide SIFamide (SIFa). Although the sequence and spatial expression of SIFa are evolutionarily conserved among insect species, the physiological function of SIFa/SIFR signaling remains elusive. Here, we provide genetic evidence that SIFa and SIFR promote sleep in Drosophila. Either genetic ablation of SIFa-expressing neurons in the pars intercerebralis (PI) or pan-neuronal depletion of SIFa expression shortened baseline sleep and reduced sleep-bout length, suggesting that it caused sleep fragmentation. Consistently, RNA interference-mediated knockdown of SIFR expression caused short sleep phenotypes as observed in SIFa-ablated or depleted flies. Using a panel of neuron-specific Gal4 drivers, we further mapped SIFR effects to subsets of PI neurons. Taken together, these results reveal a novel physiological role of the neuropeptide SIFa/SIFR pathway to regulate sleep through sleep-promoting neural circuits in the PI of adult fly brains.

• BMB Reports
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• 제48권12호
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• pp.645-646
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• 2015

The sympathetic nervous system (SNS) or neurotransmitters in the bone marrow microenvironment has been known to regulate hematopoietic stem cell (HSC) functions such as self-renewal, proliferation and differentiation. However, the specific role of neuropeptide Y (NPY) in this process remains relatively unexplored. In this study, we demonstrated that NPY deficient mice have significantly reduced HSC numbers and impaired bone marrow regeneration due to apoptotic destruction of SNS fibers and/or endothelial cells. Moreover, NPY treatment prevented bone marrow impairments in a mouse model of chemotherapy-induced SNS injury, while conditional knockout mice lacking the Y1 receptor in macrophages did not restore bone marrow dysfunction in spite of NPY injection. Transforming growth factor-beta (TGF-β) secreted by NPY-mediated Y1 receptor stimulation in macrophages plays a key role in neuroprotection and HSC survival in the bone marrow. Therefore, this study reveals a new role of NPY in bone marrow HSC microenvironment, and provides an insight into the therapeutic application of this neuropeptide.

• 생명과학회지
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• 제26권6호
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• pp.721-726
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• 2016

누에(Bombyx mori)에서 short neuropeptide F (sNPF) receptor를 encoding하고 있는 cDNA를 cloning하여서 BsNPF-R라고 이름을 붙였다. BsNPF-R는 이미 보고된 sNPF-R들과 아미노산 수준에서 사람(36%), 쥐(34%), 제브라피쉬(35%), 초파리(51%)와 상동성을 보였다. BsNPF-R는 계산적으로 분자량이 42,731 Da이고 원형질막을 관통하는 단백질이다. BsNPF-R 유전자발현은 중장, 후견사선, 말피기관, 정소에서 강한 반면 지방체, 혈세포, 난소에서 약하게 발현하였다. 그리고 합성된 sNPF에 의해서도 BsNPF-R의 유전자발현이 조절되었다.

• 생물정신의학
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• 제5권1호
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• pp.34-45
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• 1998

단가아민 신경전달물질과 신경펩타이드의 가장 큰 차이점은 합성과정에 있다. 시냅스에서의 활동과 비활성화 과정에서도 양자의 차이는 뚜렷하다. 단가아민 신경전달물질의 작용은 매우 단시간 내에 일어나며, 대개는 재흡수기전을 통해 활동이 정지되고, 일부가 효소반응에 의해 비활성물질로 대사된다. 또한 이들은 단가아민 신경전달물질들과 마찬가지로 presynaptic peptidergic receptor를 갖는다는 사실이 알려져 있으며, 신경펩타이드 분비를 조절하는 자가수용체도 갖고 있다. 신경펩타이드의 시냅스전 세포로의 재흡수기전에 대해서는 아직 밝혀져 있지 않다. 신경펩타이드들도 시냅스 후막의 수용체로 확산되어 이차전령, 삼차전령을 통해 생물학적 반응을 일으킨다는 것은 단가아민 신경전달 물질과 동일하다. 본래 신경세포는 자극에 의해 glycoproteins, enzymes, inorganic ions, metal ions, phospholipids, purines, amines, peptides 등의 물질들을 함께 분비한다. 이들 중에는 신경전달물질의 기준에 부합되는 것도 있으나, 대다수는 기능이 없다. 때로는 수 종류의 신경전달물질들과 신경신경펩타이드들이 한가지 신경전달물질의 분비에 관여하기도 한다. 저자들은 현재 임상연구에서 괄목할 만한 진전을 보이고 있는 두가지 신경펩타이드들에 대해 그 신경생물학적 측면과 임상적 측면을 고찰하였다. 알코올의 신경생리에 있어 가장 흥미있는 것은 아마 강화기전일 것이다. 내인성 opioid계 물질들이 알코올의 강화효과와 관계가 있다는 근거들은 많다. Naltrexone은 수용체 차단을 통해 이러한 강화기전을 차단함으로서 음주욕을 감소시키는 것으로 해석된다. Opioid reinforcement는 변연계의 도파민 활성화를 통해 이루어진다. 이는 알코올의 강화에 도파민이 관여한다는 사실과도 관계된다. 이를 도파민-알코올 강화 가설이라 한다. 기타 세로토닌도 알코올의 강화를 중재하는 신경전달물질로 생각되고 있다. 선택적 세로토닌 재흡수 차단제를 장기간 사용하거나, $5-HT_3$ 수용체 길항제를 사용하면 음주욕이 감소된다고 알려져 있다. 신경전달물질계간에는 중요한 상호작용이 있다. 알코올이 측중격핵에서 도파민의 분비를 촉진시키는 기전에도 여러 신경전달계의 상호작용이 관여된다. 이의 기전에 생리적 수준에서 관여되는 대표적인 물질로는 (1) opiates, (2) serotonin, (3) amino acids, (4) 기타 neuropeptide들을 들 수 있다. Opiate 수용체 길항제들은 측중격핵에서 도파민 분비를 차단하고, $5-HT_3$ 수용체 효현제는 이를 자극한다. 이들을 총체적으로 종합하면, 도파민, 세로토닌, opiate 수용체들을 조절하면 알콜리즘을 치료할 수 있다는 것이다. CCK는 흥분성 신경전달물질로 밝혀지고 있으며, 진통 및 morphine에 대한 내성형성, 포만, 기억 등의 정신병리에 일부 관여하나, 역시 최근 가장 주목을 받는 것은 CCK계가 불안의 병리에 관여한다는 소견이다. 이 분야의 연구에 기폭제가 된 것은 CCK-4가 공황발작을 유발한다는 임상 연구결과로부터 비롯된다. 이에 의한 불안반응은 자연유발된 공황발작과 거의 같으며, 정상인과 공황장애 환자를 구별하는 민감도를 갖고 있다. 이 CCK-4에 의해 유발된 공황발작은 $CCK_B$ 길항제들에 의해 차단된다. 즉 공황불안의 기전에 $CCK_B$ 수용체가 관여할 가능성이 있다. 따라서 공황발작이 $CCK_B$ 수용체의 민감도 결함으로 추정될 수 있다. 또한 이 반응은 imipramine과 benzodiazepine계 약물들에 의해 차단됨이 알려져 있다. 이 공황 불안의 형성 기전에 다른 신경전달계와의 상호작용이 있다. 본고에서는 특히 benzodiazepine계와의 상호작용 및 5-HT계와의 상호작용을 거론하였다. 향후 CCK 길항제들이 항불안제로 개발될 전망이다. 이들은 내성형성, 금단증상, 진정작용 등의 문제가 없으므로 새로운 항불안제로 기대된다.

• Clinical and Experimental Reproductive Medicine
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• 제39권2호
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• pp.87-93
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• 2012

Objective: Lin28 has been known to control the proliferation and pluripotency of embryonic stem cells. The purpose of this study was to determine the downstream effectors of Lin28 in mouse embryonic stem cells (mESCs) by RNA interference and microarray analysis. Methods: The control siRNA and Lin28 siRNA (Dharmacon) were transfected into mESCs. Total RNA was prepared from each type of transfected mESC and subjected to reverse transcription-polymerase chain reaction (RT-PCR) analysis to confirm the downregulation of Lin28. The RNAs were labeled and hybridized with an Affymetrix Gene-Chip Mouse Genome 430 2.0 array. The data analysis was accomplished by GenPlex 3.0 software. The expression levels of selected genes were confirmed by quantitative real-time RT-PCR. Results: According to the statistical analysis of the cDNA microarray, a total of 500 genes were altered in Lin28-downregulated mESCs (up-regulated, 384; down-regulated, 116). After differentially expressed gene filtering, 31 genes were selected as candidate genes regulated by Lin28 downregulation. Among them, neuropeptide Y5 receptor and oocyte-specific homeobox 5 genes were significantly upregulated in Lin28-downregulated mESCs. We also showed that the families of neuropeptide Y receptor (Npyr) and oocyte-specific homeobox (Obox) genes were upregulated by downregulation of Lin28. Conclusion: Based on the results of this study, we suggest that Lin28 controls the characteristics of mESCs through the regulation of effectors such as the Npyr and Obox families.

• Biomolecules & Therapeutics
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• 제25권1호
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• pp.57-68
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• 2017

Seven transmembrane receptors (7TMRs), also known as G protein-coupled receptors, are popular targets of drug development, particularly 7TMR systems that are activated by peptide ligands. Although many pharmaceutical drugs have been discovered via conventional bulk analysis techniques the increasing availability of structural and evolutionary data are facilitating change to rational, targeted drug design. This article discusses the appeal of neuropeptide-7TMR systems as drug targets and provides an overview of concepts in the evolution of vertebrate genomes and gene families. Subsequently, methods that use evolutionary concepts and comparative analysis techniques to aid in gene discovery, gene function identification, and novel drug design are provided along with case study examples.

• 통합자연과학논문집
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• 제10권1호
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• pp.7-13
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• 2017

Neuromedin U receptor 1 is a GPCR protein which binds with the neuropeptide, neuromedin. It is involved in the regulation of feeding and energy homeostasis and related with immune mediated inflammatory diseases like asthma. It plays an important role in maintaining the biological clock and in the regulation of smooth muscle contraction in the gastrointestinal and genitourinary tract. Analysing the structural features of the receptor is crucial in studying the pathophysiology of the diseases related to the receptor important. As the three dimensional structure of the protein is not available, in this study, we have performed the homology modelling of the receptor using 5 different templates. The models were subjected to model validation and two models were selected as optimal. These models could be helpful in analysing the structural features of neuromedin U receptor 1 and their role in disorders related to them.

• 통합자연과학논문집
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• 제10권1호
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• pp.14-19
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• 2017

Neuromedin, a neuropeptide, which is involved in various functions that include contractile activity on smooth muscle, controlling the blood flow and ion transport in the intestine, increased blood pressure and regulation of adrenocortical function. It is involved in the pathophysiology of various immune mediated inflammatory diseases like asthma. In this study, we have performed protein-protein docking analysis of neuromedin U - neuromedin U receptor 1 complex. We have developed homology models of neuromedin U, and selected a reliable model using model validation. The model was docked with the receptor model, to analyse the crucial interactions of the complex. This study could be helpful as a tool in developing novel and potent drugs for the diseases related with neuromedin U receptor 1.

• BMB Reports
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• 제49권5호
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• pp.288-292
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• 2016

Cisplatin is a platinum-based chemotherapeutic drug for treating various types of cancers. However, the use of cisplatin is limited by its negative effect on normal tissues, particularly nephrotoxicity. Various mechanisms such as DNA adduct formation, mitochondrial dysfunction, oxidative stress, and apoptosis are involved in the adverse effect induced by cisplatin treatment. Several studies have suggested that neuropeptide Y (NPY) is involved in neuroprotection as well as restoration of bone marrow dysfunction from chemotherapy induced nerve injury. However, the role of NPY in chemotherapy-induced nephrotoxicity has not been studied. Here, we show that NPY rescues renal dysfunction by reducing the expression of pro-apoptotic proteins in cisplatin induced nephrotoxicity through Y1 receptor, suggesting that NPY can protect kidney against cisplatin nephrotoxicity as a possible useful agent to prevent and treat cisplatin-induced nephrotoxicity.