• Biomolecules & Therapeutics
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• v.25 no.1
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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.

• The Korean Journal of Pharmacology
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• v.28 no.1
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• pp.49-60
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• 1992

This study was designed to evaluate the responses of cardiovascular system to endothelin (ET) and neuropeptide Y (NPY) in 12 week-old SHR treated with or without enalapril (ENP) for 6 weeks. The diastolic blood pressure and heart rate were lower in ENP-treated SHR than in control. The pressor response to intravenous, but not intracerebroventricular, ET or NPY was attenuated by ENP treatment. The chronotropic action induced by electrical stimulation was attenuated by ENP or ET. The negative chronotropic action of ET was blocked by yohimbine. The increase in aortic tension induced by electrical field stimulation (EFS) was depressed in ENP-treated group as compared with non-treated group, and enhanced by ET, but not NPY, in the non-treated group. The ET-induced increase in tension was enhanced by removal of endothelium in the control group but not in ENP-treated group. The plasma concentration of norepinephrine and ET-induced increase in concentration of norepinephrine and epinephrine in plasma were decreased in ENP-treated group. These results suggest that preventive effect of enalapril on the development of hypertension may result from depressing vasoactive action of endothelin and neuropeptide Y, and sympathetic neurotransmission at peripheral nervous system.

• Rapid Communication in Photoscience
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• v.5 no.1
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• pp.11-12
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• 2016

Schwann cells and neuronal cells from dorsal root ganglion (DRG) in embryos of rat were cultured in vitro respectively. The purified neuronal cells with anti-mitotic agents and purified Schwann cells were co-cultured and then accomplished myelination processing. Infection of Semliki forest virus into this myelinated co-culture system was performed and then accomplished demyelination. We identified myelination and demyelination processing using antibody of neuropeptide Y.

• Clinical and Experimental Reproductive Medicine
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• v.39 no.2
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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.

• Journal of Acupuncture Research
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• v.20 no.4
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• pp.93-101
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• 2003

Objective: The purpose of this study is to find out the effect of acupuncture at HT7 (Shinmun) on the feeding behavior and hypothalamic neuropeptide Y(NPY) expression in the maternally separated rat pups. Methods: To show the effect of acupuncture, we performed maternal separation(MS) for 7 days beginning on postnatal day 14, and observed body weight, food intake, and NPY immunoreactivity in the paraventricular nucleus (PVN) of hypothalamus after acupuncturing at HT7, the end of the transverse crease of the ulnar wrist of the forepaw. Results: MS induced a significant decreases in body weight and food intake, while acupuncture treatment at acupoint HT7 showed much more improvement in those evaluations. NPY-immunoreactivity in area PVN were decreased in the MS group, but significantly increased in the HT7 group. Conclusions: These findings suggest that acupuncture has an effect on the feeding disorders caused by MS, possibly by modulating NPY expression in the PVN.

• BMB Reports
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• v.49 no.5
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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.

• BMB Reports
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• v.50 no.8
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• pp.417-422
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• 2017

Cisplatin is the most effective and widely used chemotherapeutic agent for many types of cancer. Unfortunately, its clinical use is limited by its adverse effects, notably bone marrow suppression leading to abnormal hematopoiesis. We previously revealed that neuropeptide Y (NPY) is responsible for the maintenance of hematopoietic stem cell (HSC) function by protecting the sympathetic nervous system (SNS) fibers survival from chemotherapy-induced bone marrow impairment. Here, we show the NPY-mediated protective effect against bone marrow dysfunction due to cisplatin in an ovarian cancer mouse model. During chemotherapy, NPY mitigates reduction in HSC abundance and destruction of SNS fibers in the bone marrow without blocking the anticancer efficacy of cisplatin, and it results in the restoration of blood cells and amelioration of sensory neuropathy. Therefore, these results suggest that NPY can be used as a potentially effective agent to improve bone marrow dysfunction during cisplatin-based cancer therapy.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.4
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• pp.433-438
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• 1999

Two components of the neuroendocrine-hormonal response to long-term treatment of acarbose, adipose tissue-derived leptin and central neuropeptide Y (NPY), were investigated in the ICR mice on a high- carbohydrate diet. Acarbose, administered 5 or 50 mg per 100 g diet for four weeks, dose dependently suppressed body weight gain. The body weight gain was reduced along with the amount of daily food intake in 50 mg acarbose-treated group at $7^{th}\;and\;28^{th}$ day. 5 or 50 mg acarbose treatment administered for four weeks reduced leptin mRNA levels to 62% and 77% of the control group, demonstrating that the amount of leptin mRNA in adipocytes correlates with body weight. As dose of acarbose increased, leptin mRNA level also increased, suggesting that potent inhibition of ${\alpha}-glycosidase$ by a higher dose of acarbose furthers the enzyme activity and leptin gene consequently. On the other hand, central expression level of NPY gene was increased significantly compared with the control group at the same amount of acarbose administered, reflecting that leptin and NPY operate in a negative-feedback circuit to regulate body fat stores.

• The Journal of Korean Medicine
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• v.27 no.3 s.67
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• pp.1-13
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• 2006

The purpose of this study was to investigate the anti-obesity effects of crude saponin (CS) in Korean red ginseng (KRG) on rats fed a high fat (HF) diet. Methods: Male Sprague-Dawley (SD) rats were divided into a normal diet group and a high-fat (HF) diet group. The HF diet group became obese from being fed a HF diet over five weeks. The normal diet group were fed a normal diet. Each CS group of the normal diet group and HF diet group was administered CS (200 mg/kg, i.p.) for three weeks, the control group of both types was administered normal saline (1ml/kg, i.p.) instead of CS. Each group had 5 rats. Results: After administration of CS, the body weight, food consumption, adipose tissues, and expression of appetite peptides such as leptin and neuropeptide-Y (NPY) were investigated in the HF diet group as well as the normal diet group. Administration of CS reduced body weight, food intake, and fat content in the HF and normal diet groups. After CS administration, NPY expression and leptin were lower in the HF diet group. Conclusions: Our results suggest that CS may be useful in the treatment of obesity, especially of type qixu (氣虛).

• BMB Reports
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• v.50 no.3
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• pp.138-143
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• 2017

Ovariectomy-induced bone loss is related to an increased deposition of osteoclasts on bone surfaces. We reported that the 36-amino-acid-long neuropeptide Y (NPY) could mobilize hematopoietic stem/progenitor cells (HSPCs) from the bone marrow to the peripheral blood by regulating HSPC maintenance factors and that mobilization of HSPCs ameliorated low bone density in an ovariectomy-induced osteoporosis mouse model by reducing the number of osteoclasts. Here, we demonstrated that new NPY peptides, recombined from the cleavage of the full-length NPY, showed better functionality for HSPC mobilization than the full-length peptide. These recombinant peptides mediated HSPC mobilization with greater efficiency by decreasing HSPC maintenance factors. Furthermore, treatment with these peptides reduced the number of osteoclasts and relieved ovariectomy-induced bone loss in mice more effectively than treatment with full-length NPY. Therefore, these results suggest that peptides recombined from full-length NPY can be used to treat osteoporosis.