• 제목/요약/키워드: KiSS-1

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홍바리 Epinephelus fasciatus의 KiSS1, KiSS2, GPR54 mRNA 발현양상 (KiSS1, KiSS2, GPR54 mRNA Expression of the Blacktip Grouper Epinephelus fasciatus)

  • 강형철;이치훈;송영보;백혜자;김형배;이영돈
    • 한국발생생물학회지:발생과생식
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    • 제16권2호
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    • pp.121-128
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    • 2012
  • 최근 여러 포유류 종에서 Kisspeptin이 그 수용체인 GPR54와 함께 GnRH 분비를 자극하여 성 성숙과 최종배란에 영향을 미친다고 보고되고 있다. 이러한 보고들은 KiSS-GPR54 system이 번식과 밀접한 연관이 있음을 제시하고 있지만, 어류에 관한 연구는 미비한 실정이다. 이 연구는 어류에서의 KiSS-GPR54 system의 생리적 기능과 번식내분비적 기능을 탐색하기 위해 홍바리 Epinephelus fasciatus 뇌에서 KiSS1, KiSS2, GPR54 mRNA의 부분 염기서열을 클로닝 하였으며, KiSS1, KiSS2, GPR54 mRNA의 각 조직별 발현을 RT-PCR을 이용하여 확인하였다. 성 성숙과 KiSS-GPR54 system과의 연관성을 확인하기 위해 생식소 발달 상태(성숙과 미성숙)에 따른 발현을 qRT-PCR을 이용하여 분석하였다. KiSS1, KiSS2, GPR54의 부분 염기서열은 각각 232 bp, 304 bp, 613 bp 였으며, 조직별 발현을 조사한 결과 공통적으로 뇌에서 발현되었다. 생식소발달에 따른 발현 양상은 KiSS1, KiSS2 mRNA의 경우 성숙 상태에서가 미성숙 상태에 비해 유의적으로 높게 발현되었다. 하지만 GPR54 mRNA의 경우 미성숙 상태에서 더 높게 발현되었다. 이러한 결과들로 미루어 보아, KiSS-GPR54 system은 홍바리에 있어 번식과 밀접한 관련이 있을 것으로 사료된다.

Evaluation of KiSS1 as a Prognostic Biomarker in North Indian Breast Cancer Cases

  • Singh, Richa;Bhatt, Madan Lal Brahma;Singh, Saurabh Pratap;Kumar, Vijay;Goel, Madhu Mati;Mishra, Durga Prasad;Kumar, Rajendra
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권4호
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    • pp.1789-1795
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    • 2016
  • Background: Breast cancer is the commonest female cancer worldwide and its propensity to metastasize negatively impacts on therapeutic outcome. Several clinicopathological parameters with prognostic/predictive significance have been associated with metastatic suppressor expression levels. The role of metastatic suppressor gene (MSG) KiSS1 in breast cancer remains unclear. Our goal was to investigate the possible clinical significance of KiSS1 breast cancer. Materials and Methods: The study was conducted on 87 histologically proven cases of breast cancer and background normal tiisue. Quantitative reverse transcriptase polymerase chain reaction (qRT PCR) and immunohistochemistry (IHC) were used to investigate KiSS1 at gene and protein levels, respectively, for correlation with several patient characteristics including age, family history, hormonal receptor status, stage, tumor size, nodal involvement and metastatic manifestation and finally with median overall survival (OS). Results: Our study revealed (i) KiSS1 levels were generally elevated in breast cancer vs normal tissue (P < 0.05). (ii) however, a statistically significant lower expression of KiSS1 was observed in metastatic vs non metastatic cases (P = 0.04). (iii) KiSS1 levels strongly correlated with T,N,M category, histological grade and advanced stage (p<0.001) but not other studied parameters. (iv) Lastly, a significant correlation between expression of KiSS1 and median OS was found (P = 0.04). Conclusions: Conclusively, less elevated KiSS1 expression is a negative prognostic factor for OS, advancing tumor stage, axillary lymph node status, metastatic propensity and advancing grade of the breast cancer patient. Patients with negative KiSS1 expression may require a more intensive therapeutic strategy.

Overexpression of KiSS1 Induces the Proliferation of Hepatocarcinoma and Increases Metastatic Potential by Increasing Migratory Ability and Angiogenic Capacity

  • Cho-Won, Kim;Hong, Kyu, Lee;Min-Woo, Nam;Youngdong, Choi;Kyung-Chul, Choi
    • Molecules and Cells
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    • 제45권12호
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    • pp.935-949
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    • 2022
  • Liver cancer has a high prevalence, with majority of the cases presenting as hepatocellular carcinoma (HCC). The prognosis of metastatic HCC has hardly improved over the past decade, highlighting the necessity for liver cancer research. Studies have reported the ability of the KiSS1 gene to inhibit the growth or metastasis of liver cancer, but contradictory research results are also emerging. We, therefore, sought to investigate the effects of KiSS1 on growth and migration in human HCC cells. HepG2 human HCC cells were infected with lentivirus particles containing KiSS1. The overexpression of KiSS1 resulted in an increased proliferation rate of HCC cells. Quantitative polymerase chain reaction and immunoblotting revealed increased Akt activity, and downregulation of the G1/S phase cell cycle inhibitors. A significant increase in tumor spheroid formation with upregulation of β-catenin and CD133 was also observed. KiSS1 overexpression promoted the migratory, invasive ability, and metastatic capacity of the hepatocarcinoma cell line, and these effects were associated with changes in the expressions of epithelial mesenchymal transition (EMT)- related genes such as E-cadherin, N-cadherin, and slug. KiSS1 overexpression also resulted in dramatically increased tumor growth in the xenograft mouse model, and upregulation of proliferating cell nuclear antigen (PCNA) and Ki-67 in the HCC tumors. Furthermore, KiSS1 increased the angiogenic capacity by upregulation of the vascular endothelial growth factor A (VEGF-A) and CD31. Based on these observations, we infer that KiSS1 not only induces HCC proliferation, but also increases the metastatic potential by increasing the migratory ability and angiogenic capacity.

Excess of leptin inhibits hypothalamic KiSS-1 expression in pubertal mice

  • Ahn, Sung-Yeon;Yang, Sei-Won;Lee, Hee-Jae;Byun, Jong-Seon;Om, Ji-Yeon;Shin, Choong-Ho
    • Clinical and Experimental Pediatrics
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    • 제55권9호
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    • pp.337-343
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    • 2012
  • Purpose: Leptin has been considered a link between metabolic state and reproductive activity. Defective reproductive function can occur in leptin-deficient and leptin-excessive conditions. The aim of this study was to examine the effects of centrally injected leptin on the hypothalamic KiSS-1 system in relation to gonadotropin-releasing hormone (GnRH) action in the initial stage of puberty. Methods: Leptin (1 ${\mu}g$) was injected directly into the ventricle of pubertal female mice. The resultant gene expressions of hypothalamic GnRH and KiSS-1 and pituitary LH, 2 and 4 hours after injection, were compared with those of saline-injected control mice. The changes in the gene expressions after blocking the GnRH action were also analyzed. Results: The basal expression levels of KiSS-1, GnRH, and LH were significantly higher in the pubertal mice than in the prepubertal mice. The 1-${\mu}g$ leptin dose significantly decreased the mRNA expression levels of KiSS-1, GnRH, and LH in the pubertal mice. A GnRH antagonist significantly increased the KiSS-1 and GnRH mRNA expression levels, and the additional leptin injection decreased the gene expression levels compared with those in the control group. Conclusion: The excess leptin might have suppressed the central reproductive axis in the pubertal mice by inhibiting the KiSS-1 expression, and this mechanism is independent of the GnRH-LH-estradiol feedback loop.

KiSS-1 : 포유동물 생식계에서의 새로운 신경펩타이드 (KiSS-1 : A Novel Neuropeptide in Mammalian Reproductive System)

  • 이성호;최돈찬
    • 한국발생생물학회지:발생과생식
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    • 제9권1호
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    • pp.1-5
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    • 2005
  • 시상하부-뇌하수체-생식소(HPG) 호르몬 축은 유아기와 아동기에는 작동하지 않다가 사춘기 개시 직전에 활성화되는 흥분성 및 억제성 신호들의 복잡한 중추성 조절 네트워크에 의해 조절된다. 최근 주목받고 있는 kisspeptin은 KiSS-1 유전자의 펩타이드 산물로, 최초 orphan receptor로 클로닝된 G protein-coupled receptor 54(GPR54)의 내인성 리간드이다. KiSS-l은 본래 종양전이억제 유전자로 알려졌으나, 최근의 연구들은 KiSS-1/GPR54 시스템이 생식계의 주요한 조절자임을 시사하고 있다. 비록 생식 관련 호르몬 분비의 신경내분비적 조절에서 KiSS-1/GPR54 시스템의 정확한 역할은 아직 자세히 모르지만, 이 시스템은 생식호르몬 축에서의 일차적인 연결 고리일 수 있다. 중추적(icv) 또는 말초적(sc 또는 ip)으로 kisspeptin을 주사할 경우 시상하부-뇌하수체-생식소 축이 자극되어 혈중 LH 수준이 증가함이 설치류, 양, 원숭이 그리고 인간을 대상으로 한 실험들에서 관찰되었다. 이러한 kisspeptin의 효과는 시상하부 GnRH 신경계를 경유하여 나타나는 것으로 보이지만, 뇌하수체 전엽에 직접 작용할 수도 있다. GPR54 녹아웃 생쥐에서는 사춘기 개시의 소실과 생식소자극호르몬 저하성 생식소 기능저하증(hypogonadotropic hypogonadism, HH)이 나타났다. 따라서 kisspeptin 주사는 인간의 생식계 이상을 치료하기 위한 HPG 축을 활성화시키는 치료에 응용할 수 있을 것이다.

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Structure Prediction of KiSS1-derived Peptide Receptor Using Comparative Modelling

  • Nagarajan, Santhosh Kumar;Madhavan, Thirumurthy
    • 통합자연과학논문집
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    • 제9권2호
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    • pp.136-143
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    • 2016
  • KiSS1-derived peptide receptor, a GPCR protein, binds with the hormone kiss peptin. They are important in the neuroendocrine regulation of reproduction and in the secretion of gonadotrophin-releasing hormone. Thus, analysing the structural features of the receptor becomes important. However, the three dimensional structure of the protein is unavailable. Hence in this study, we have performed the homology modelling of KiSS1-derived peptide receptor with 5 different templates. 30 models were constructed using two platforms - Easymodeller and ITasser. The optimal models were chosen based on the model validation. Two models were selected after validation. The developed models could provide useful for analysing the structural features of KiSS1-derived peptide receptor and their pathophysiological role in various disorders related to them.

Kisspeptins (KiSS-1): Essential Players in Suppressing Tumor Metastasis

  • Prabhu, Venugopal Vinod;Sakthivel, Kunnathur Murugesan;Guruvayoorappan, Chandrasekharan
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권11호
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    • pp.6215-6220
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    • 2013
  • Kisspeptins (KPs) encoded by the KiSS-1 gene are C-terminally amidated peptide products, including KP-10, KP-13, KP-14 and KP-54, which are endogenous agonists for the G-protein coupled receptor-54 (GPR54). Functional analyses have demonstrated fundamental roles of KiSS-1 in whole body homeostasis including sexual differentiation of brain, action on sex steroids and metabolic regulation of fertility essential for human puberty and maintenance of adult reproduction. In addition, intensive recent investigations have provided substantial evidence suggesting roles of Kisspeptin signalling via its receptor GPR54 in the suppression of metastasis with a variety of cancers. The present review highlights the latest studies regarding the role of Kisspeptins and the KiSS-1 gene in tumor progression and also suggests targeting the KiSS-1/GPR54 system may represent a novel therapeutic approach for cancers. Further investigations are essential to elucidate the complex pathways regulated by the Kisspeptins and how these pathways might be involved in the suppression of metastasis across a range of cancers.

Protein-Protein Interaction Analysis of KiSS1-Derived Peptide Receptor with Kisspeptin-10 and Kisspeptin-15

  • Nagarajan, Santhosh Kumar
    • 통합자연과학논문집
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    • 제11권1호
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    • pp.9-13
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    • 2018
  • KiSS1-derived peptide receptor, a GPCR protein, binds with the hormone Kisspeptin plays a major role in the neuroendocrine regulation of reproduction. It is important in the onset of puberty and triggers the release of gonadotrophin-releasing hormone. It is a potential drug target for the disorders related to GnRH, hence, analysing the structural features of the receptor becomes important. The three dimensional of the receptor modelled in a previous study was utilised. In this study, we have analysed the protein - protein interaction of the receptor with Kisspeptin 10 and 15. The study revealed the important residues which are involved in the interaction. The result of this study could be helpful in understanding the mechanism of Kiss1 receptor activation and the pathophysiology of the disorders related to the receptor.

강우 시 도시 하천으로의 비점오염원 유출특성 (The runoff characteristics of non-point source to urban stream during rainfall)

  • 박운지;김동욱;안종화;이찬기
    • 산업기술연구
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    • 제27권B호
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    • pp.83-89
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    • 2007
  • We studied runoff characteristics of combined sewer overflows in a city while it was raining. The event mean concentration (EMC) of biochemical oxygen demand (BOD), chemical oxygen demand ($COD_{Cr}$), suspended solids (SS), total nitrogen (TN), and total phosphorus (TP) in one of the combined sewer sites in Chuncheon was 63.5-211.6 mg/L, 114.9-523.8 mg/L, 70.3-436.4 mg/L, 6.4-33.0 mg/L, and 1.09-6.81 mg/L, respectively. In another combined sewer, the EMC of BOD, COD, SS, TN, and TP was 42.1-131.4 mg/L, 107.7-256.5 mg/L, 33.7-221.1 mg/L, 7.9-26.4 mg/L, and 1.16-3.91 mg/L, respectively. The ratio of the cumulative pollutant mass and the cumulative discharged volume determined using all parameters (BOD, $COD_{Cr}$, SS, TN, and TP) was over 1.0, which shows the first flush effect. Relationships between flow and loadings of BOD, $COD_{Cr}$, SS, TN, and TP were 0.90, 0.89, 0.88, 0.89, 0.92, respectively. Although the size of two areas was almost same, pollutant concentration and loading were different because of the amount of rainfall, rainfall intensity and basin area.

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Type I Interferon Increases Inflammasomes Associated Pyroptosis in the Salivary Glands of Patients with Primary Sjögren's Syndrome

  • Seung-Min Hong;Jaeseon Lee;Se Gwang Jang;Jennifer Lee;Mi-La Cho;Seung-Ki Kwok;Sung-Hwan Park
    • IMMUNE NETWORK
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    • 제20권5호
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    • pp.39.1-39.13
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    • 2020
  • Sjögren's syndrome (SS) is a chronic and systemic autoimmune disease characterized by lymphocytic infiltration in the exocrine glands. In SS, type I IFN has a pathogenic role, and recently, inflammasome activation has been observed in both immune and non-immune cells. However, the relationship between type I IFN and inflammasome-associated pyroptosis in SS has not been studied. We measured IL-18, caspase-1, and IFN-stimulated gene 15 (ISG15) in saliva and serum, and compared whether the expression levels of inflammasome and pyroptosis components, including absent in melanoma 2 (AIM2), NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), caspase-1, gasdermin D (GSDMD), and gasdermin E (GSDME), in minor salivary gland (MSG) are related to the expression levels of type I IFN signature genes. Expression of type I IFN signature genes was correlated with mRNA levels of caspase-1 and GSDMD in MSG. In confocal analysis, the expression of caspase-1 and GSDMD was higher in salivary gland epithelial cells (SGECs) from SS patients. In the type I IFN-treated human salivary gland epithelial cell line, the expression of caspase-1 and GSDMD was increased, and pyroptosis was accelerated in a caspase-dependent manner upon inflammasome activation. In conclusion, we demonstrate that type I IFN may contribute to inflammasome-associated pyroptosis of the SGECs of SS patients, suggesting another pathogenic role of type I IFN in SS in terms of target tissue -SGECs destruction.