• KSBB Journal
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• 제21권6호
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• pp.466-473
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• 2006

본 연구에서는 췌장 베타세포의 인슐린 분비 촉진 물질로 선별된 방선균 배양액에서 유래한 YHB-2017 (genistein)의 인슐린 분비 촉진 활성의 특성을 조사하고 그 작용 기전을 밝히고자 하였다. YHB-2017는 췌장소도에서 glucose 농도가 16 mM일 때 농도 의존적으로 인슐린 분비를 대조군에 비해 2배 이상 촉진시켰으며, 5.5 mM 이하의 glucose 농도에서는 인슐린 분비 촉진 활성이 거의 없는 것으로 나타났다. MIN6 세포를 이용한 YHB-2017의 인슐린 분비 촉진 활성 특성을 분석한 결과, PKA inhibitor (H89)에 의해서 활성이 저해되었으며, 세포막의 $K_{ATP}$ channel를 배제하고 단순히 칼슘이온을 최대로 세포내로 유입시킨 조건인 diazoxide ($200\;{mu}M$)와 KCI (35 mM)를 첨가한 경우에 YHB-2017는 인슐린 분비 촉진 활성을 나타내 $K_{ATP}$ channel-independent pathway를 통한 인슐린 분비 촉진 기전을 추정할 수 있었다. 베타세포의 단백질 인산화에 대한 영향을 조사한 결과 YHB-2017는 고농도 glucose 조건에서만 PKA 기질과 cAMP response element-binding protein (CREB)의 인산화를 증가시키는 것으로 나타났고, PKC 기질의 인산화에는 영향이 없었다. 또한, YHB-2017를 18시간동안 베타세포에 처리하였으나 인슐린 유전자 발현에는 영향을 주지 않았다. 이상의 결과를 종합하여 볼 때 YHB-2017는 기존의 sulphonylurea 계열 약물과는 다른 작용 기전에 의해 췌장 베타세포에서 인슐린 분비를 촉진시키며, 그 기전은 PKA경로를 통해 amplify 신호를 활성화시키는데 관여하는 것으로 추정된다.

• The Korean Journal of Physiology and Pharmacology
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• 제8권4호
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• pp.227-235
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• 2004

The aim of the present study was to examine the effect of leptin on CA release from the isolated perfused model of the rat adrenal gland, and to establish its mechanism of action. Leptin $(1{\sim}100\;ng/ml)$, when perfused into an adrenal vein of the rat adrenal gland for 60 min, enhanced a dose-dependently the secretory responses of CA evoked by ACh $(5.32{\times}10^{-3}\;M)$, DMPP $(10^{-4}\;M)$ and McN-A-343 $(10^{-4}\;M)$, although it alone has weak effect on CA secretion. However, it did not affect the CA secretion evoked by excess $K^+\;(5.6{\times}10^{-2}\;M)$. Leptin alone produced a weak secretory response of the CA. Moreover, leptin (10 ng/ml) in to an adrenal vein for 60 min also augmented the CA release evoked by BAY-K-8644, an activator of the dihydropyridine L-type $Ca^{2+}$ channels, and cyclopiazonic acid, an inhibitor of cytoplasmic $Ca^{2+}$ ATPase. However, in the presence of U0126 $(1\;{\mu}M)$, an inhibitor of mitogen-activated protein kinase (MAPK), leptin no longer enhanced the CA secretion evoked by ACh and DMPP. Furthermore, in the presence of anti-leptin (10 ng/ml), an antagonist of Ob receptor, leptin (10 ng/ml) also no longer potentiated the CA secretory responses evoked by DMPP and Bay-K-8644. Collectively, these experimental results suggest that leptin enhances the CA secretion from the rat adrenal medulla evoked by cholinergic stimulation (both nicotininc and muscarinic receptors), but does not that by membrane depolarization. It seems that this enhanced effect of leptin may be mediated by activation of U0126-sensitive MAPK through the leptin receptors, which is probably relevant to the activation of the dihydropyridine L-type $Ca^{2+}$ channels located on the rat adrenomedullary chromaffin cells.

• KSBB Journal
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• 제23권2호
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• pp.142-146
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• 2008

본 연구에서는 U-373-MG 세포를 이용하여 오디 추출물과 VEGF에 의한 MMPs 및 플라스민의 분비에 미치는 영향을 확인하고자 하였다. U-373-MG 세포에 오디 추출물을 $100{\sim}600\;{\mu}g/mL$의 농도로 처리한 결과, MMP-2의 분비는 거의 완벽하게 억제되었고 MMP-9의 분비는 약 $1.6{\sim}5.9$배 증가하였다. 이에 비해 플라스민의 분비는 오디 추출물 농도 $500{\sim}600\;{\mu}g/mL$에서 $36%{\sim}58%$ 감소하였다. 오디 추출물과 VEGF를 병용처리한 경우, MMP-2의 분비는 VEGF만을 처리한 것과 비교하여 약 85.5% 감소하였고, MMP-9의 분비는 약 89.8% 감소하였다. 또한, U-373-MG 세포에서 오디 추출물($100\;{\mu}g/mL$)에 의한 MMP-2와 MMP-9의 분비 증가와 플라스민 분비증가는 PI 3'-kinase 경로에 의존적이었다. 본 연구 결과를 통해 오디 추출물이 VEGF의 과발현에 따른 암의 성장을 억제 조절하는데 이용될 수 있는 가능성을 확인하였다.

• Genomics & Informatics
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• 제5권2호
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• pp.77-82
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• 2007

Serotonin (5-HT), the endogenous nonselective 5-HT receptor agonist, activates the inositol-1,4,5-triphosphate/calcium $(InsP3/Ca^{2+})$ signaling pathway and exerts both stimulatory and inhibitory actions on cAMP production and neuromodulin secretion in rat hypothalamic neurons. Specific mRNA transcripts for 5-HT1A, 5-HT2C and 5-HT4 were identified in rat hypothalamic neurons. These experiments were supported by combined techniques such as cAMP and a $Ca^{2+}$ assays in order to elucidate the associated receptors and signaling pathways. The cAMP production and neuromodulin release were profoundly inhibited during the activation of the Gi-coupled 5-HT1A receptor. Treatment with a selective agonist to activate the Gq-coupled 5-HT2C receptor stimulated InsP3 production and caused $Ca^{2+}$ release from the sarcoplasmic reticulum. Selective activation of the Gs-coupled 5-HT4 receptor also stimulated cAMP production, and caused an increase in neuromodulin secretion. These findings demonstrate the ability of 5-HT receptor subtypes expressed in neurons to induce neuromodulin production. This leads to the activation of single or multiple G-proteins which regulate the $InsP3/Ca^{2+}/PLC-{\gamma}$ and adenyl cyclase / cAMP signaling pathways.

• Asian Pacific Journal of Cancer Prevention
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• 제16권1호
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• pp.221-225
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• 2015

As metformin can inhibit endometrial carcinoma (EC) cell growth and the insulin growth factor (IGF) system is active in EC, the question of whether it can regulate endometrial carcinoma cell secretion of IGF-1 or expression of IGF-1 receptor (IGF-1R) is of interest. In this study, serum IGF-1 levels in EC patients were found to be comparable with that in the non EC patients (p>0.05). However, the IGF-1 level in the medium of cultured cells after treatment with metformin was decreased (p<0.05). IGF-1R was highly expressed in human endometrial carcinoma paraffin sections, but IGF-1R and phosphor-protein kinase B/protein kinase B (p-Akt/Akt) expression was down-regulated after metformin treatment (p<0.05). In summary, metformin can reduce the secretion of IGF-1 by Ishikawa and JEC EC cell lines and their expression of IGF-1R to deactivate downstream signaling involving the PI-3K/Akt pathway to inhibit endometrial carcinoma cell growth.

• Toxicological Research
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• 제30권2호
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• pp.77-81
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• 2014

In contrast to animals, plants do not have a circulatory system as well as mobile immune cells that allow them to protect themselves against pathogens. Instead, plants exclusively depend on the innate immune system to defend against pathogens. As typically observed in the animal innate immunity, plant immune responses are composed of pathogen detection, defense signaling which includes transcriptional reprogramming, and secretion of antimicrobial compounds. Although knowledge on recognition and subsequent signaling of pathogen-derived molecules called elicitors is now expanding, the mechanisms of how these immune molecules are excreted are yet poorly understood. Therefore, current understandings of how plants secrete defense products especially via exocytosis will be discussed in this review.

• 대한의생명과학회지
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• 제28권2호
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• pp.59-66
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• 2022

The Cyr61/CTGF/NOV (CCN) family is dynamically expressed in various tissues, including the nervous system, from the prenatal period to adulthood. However, major studies have been conducted only in limited fields, such as the cardiovascular and muscular systems, skeletal development, and cancer. In addition, although the CCN family is a secretory protein, very few studies have described its mechanism of secretion. Recently, it has been suggested that overexpression of CCN3 or intracellular accumulation due to problems in the secretory pathway can inhibit neuronal axonal growth. In this review, we have briefly summarized the structure and characteristics of the CCN family and its related diseases, with particular emphasis on the secretory mechanism and modifiers of the CCN family, newly identified in the nervous system.

• Genomics & Informatics
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• 제12권4호
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• pp.195-202
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• 2014

Metabolic syndrome (MetS) is a complex disorder related to insulin resistance, obesity, and inflammation. Genetic and environmental factors also contribute to the development of MetS, and through genome-wide association studies (GWASs), important susceptibility loci have been identified. However, GWASs focus more on individual single-nucleotide polymorphisms (SNPs), explaining only a small portion of genetic heritability. To overcome this limitation, pathway analyses are being applied to GWAS datasets. The aim of this study is to elucidate the biological pathways involved in the pathogenesis of MetS through pathway analysis. Cohort data from the Korea Associated Resource (KARE) was used for analysis, which include 8,842 individuals (age, $52.2{\pm}8.9years$ ; body mass index, $24.6{\pm}3.2kg/m^2$). A total of 312,121 autosomal SNPs were obtained after quality control. Pathway analysis was conducted using Meta-analysis Gene-Set Enrichment of Variant Associations (MAGENTA) to discover the biological pathways associated with MetS. In the discovery phase, SNPs from chromosome 12, including rs11066280, rs2074356, and rs12229654, were associated with MetS (p < $5{\times}10^{-6}$), and rs11066280 satisfied the Bonferroni-corrected cutoff (unadjusted p < $1.38{\times}10^{-7}$, Bonferroni-adjusted p < 0.05). Through pathway analysis, biological pathways, including electron carrier activity, signaling by platelet-derived growth factor (PDGF), the mitogen-activated protein kinase kinase kinase cascade, PDGF binding, peroxisome proliferator-activated receptor (PPAR) signaling, and DNA repair, were associated with MetS. Through pathway analysis of MetS, pathways related with PDGF, mitogen-activated protein kinase, and PPAR signaling, as well as nucleic acid binding, protein secretion, and DNA repair, were identified. Further studies will be needed to clarify the genetic pathogenesis leading to MetS.

• 대한미생물학회지
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• 제35권5_6호
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• pp.350-350
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• 2000

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.268.2-269
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• 2002

The recombinant histamine-releasing factor (rHRF) has been reported to induce a secretion of histamine and cytokines from inflammation-related cell types such as basophils and eosinophils. and to function as a growth factor in immune B cells. Recently. decreased expression level of HRF protein was observed in brain of patients with Alzheimer disease and Downs syndrome. suggesting a possible significant role in neurological systems. (omitted)