• 생명과학회지
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• 제32권6호
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• pp.476-481
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• 2022

유비퀴틴화는 단백질 안정성 조절을 통해 진핵세포 내 광범위한 과정에서 주요한 역할을 한다. 이 과정에서 탈유비퀴틴화 효소인 deubiquitinating enzymes (DUBs)은 표적단백질의 유비퀴틴 혹은 ubiquitin-like proteins에 결합하여 표적단백질의 분해를 억제하는 기능을 한다. DUBs의 역할은 주로 암생물학에서 다루어져 왔으며, 이를 통해 다양한 암 치료용 DUBs 억제제가 개발 중인 상황이다. 한편, 최근의 연구는 이러한 DUBs가 비만, 당뇨, 지방간을 포함한 대사질환에서 주요한 역할을 할 수 있을 것이라고 보고했다. 대사질환의 발생 및 진행에 있어 각기 다른 종류의 DUBs는 양적 혹은 음적 조절 작용을 갖음을 제시하였다. DUBs는 세포 내 다양한 전사인자의 단백질 발현 등 조절함으로써 대사질환의 발생 및 진행에 기여할 수 있음 생체 내, 외 및 인간 조직을 활용한 연구에서 입증되었다. UCH, USP7 및 USP19는 지방세포의 분화, 체중 증가, 및 인슐린 저항성에 관련이 있음을 식이 혹은 유전자조작으로 인한 비만 유도 마우스에서 검증하였다. CYLD, USP4 및 USP18의 경우 지방간의 발생과 밀접한 관계를 갖는다고 보고되었으며 이는 경우에 따라 체중 변화를 동반한다. 종합적으로, 본 총설에서는 비만 및 이와 관련한 대사질환에서 DUBs의 역할에 대한 최신 연구 결과 및 동향에 대해 기술하였다. 또한 DUBs에 새로운 역할에 관한 기초지식 및 분자적메커니즘을 제공함으로써 궁극적으로는 DUBs가 대사질환의 새로운 유전자 타겟이 될 수 있음을 시사한다.

• Asian-Australasian Journal of Animal Sciences
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• 제26권8호
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• pp.1189-1196
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• 2013

Adipose tissue development and function play a critical role in the regulation of energy balance, lipid metabolism, and the pathophysiology of metabolic syndromes. Although the effect of zinc ascorbate supplementation in diabetes or glycemic control is known in humans, the underlying mechanism is not well described. Here, we investigated the effect of a zinc-chelated vitamin C (ZnC) compound on the adipogenic differentiation of 3T3-L1 preadipocytes. Treatment with ZnC for 8 d significantly promoted adipogenesis, which was characterized by increased glycerol-3-phosphate dehydrogenase activity and intracellular lipid accumulation in 3T3-L1 cells. Meanwhile, ZnC induced a pronounced up-regulation of the expression of glucose transporter type 4 (GLUT4) and the adipocyte-specific gene adipocyte protein 2 (aP2). Analysis of mRNA and protein levels further showed that ZnC increased the sequential expression of peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) and CCAAT/enhancer-binding protein alpha (C/$EBP{\alpha}$), the key transcription factors of adipogenesis. These results indicate that ZnC could promote adipogenesis through $PPAR{\gamma}$ and C/$EBP{\alpha}$, which act synergistically for the expression of aP2 and GLUT4, leading to the generation of insulin-responsive adipocytes and can thereby be useful as a novel therapeutic agent for the management of diabetes and related metabolic disorders.

• KSBB Journal
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• 제17권3호
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• pp.283-289
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• 2002

Insulin-like growth factor-I(IGF-I)은 성장호르몬의 여러 가지 성정촉진 작용을 매개하는 분열 유발성 폴리펩티드이며, 조직의 수선과 재생, 창상치유 및 골대사와 같은 과정들에서 중요한 역할을 하는 것으로 알려져 있고, 비교적 여러 조직에서 발현되고 있는 IGF-I 유전자의 전사조절에 대한 정확한 분자적 기전과 호르몬 및 대사 상태가 그것을 어떻게 조절하는지 아직 밝혀져 있지 않다. 쥐를 절삭시키므로써 대사 상태를 변조시켰을 때, 간 조직내 IGF-I mRNA의 발현에 미치는 절식의 영향을 살펴보기 위하여 solution hybridizatioon/RNase protection 방법으로 분석 하였다. IGF-I의 exon 1 및 exon 2에 의하여 encode된 tran-scripts 모두가 감소된 결과를 얻었고, 이러한 감소는 전사 수준에서 일어난 것으로 nuclear run-on 분석에 의하여 확인하였다. 또한 절식시킨 쥐에서 IGF-I mRNA의 양을 조절하는 cia-acting elements를 IGF-I 유전자의 5'-flanking 지역과 exon 1과 econ 2에서 밝히고자 절식시킨 쥐의 신선한 간조직에서 핵 추출물을 얻어 IGF-I의 여러 가지 DNA fragments와 반응시켜 DNase I protection 분석을 한 결과, IGF-I 유전자의 주요한 전사 개 시점으로부터 downstream에 있는 sequences가 절식으로 변조시킨 대사상태에서 IGF-I의 발현 조절에 중요하며 이곳에는 전사인자인 C/EBP family의 isoform들을 포함한 간조직에 풍부하게 존재하는 여러 전사인자들이 결합할 것으로 제안하였다.

• Journal of Microbiology and Biotechnology
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• 제30권2호
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• pp.248-258
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• 2020

The vaginal microbiota may be important for pregnancy prognosis because vaginal dysbiosis during pregnancy appears to be related to preterm birth (PTB) or pregnancy loss. Previous reports have indicated that a Lactobacillus-poor microbial flora in the vagina and intrauterine infection by diverse anaerobes ascending from the vagina are associated with undesirable delivery outcomes. However, no research has involved the use of pyrosequencing analysis to examine vaginal microbiota profiles or their potential associations with high-risk pregnancy in Korean women. Vaginal swabs were collected from 500 Korean women for the identification of community state types (CSTs). Of these, 137 samples were further analyzed using a Roche/454 GS Junior pyrosequencer. Three distinct CSTs were identified based on the dominant vaginal microbes: CST I (Lactobacillus crispatus dominated), CST III (Lactobacillus iners dominated), and CST IV (with diverse species of anaerobes). Twelve of the 67 pregnant women had undesirable pregnancy outcomes (four miscarriages and eight PTBs). The dominant microbe in the vaginal microbiota of women who gave birth at full-term was L. crispatus. In contrast, L. iners was the dominant vaginal microbe in women who miscarried. Most (n = 6/8) vaginal microbiota profiles of women who experienced PTB could be classified as CST IV, with diverse bacteria, including anaerobic vaginal species. The present study provides valuable information regarding the characteristics of the vaginal microbiota of Korean women related to high-risk pregnancy. Investigation of the vaginal microbiotic structure in pregnant Korean women is necessary to enable better prediction of adverse pregnancy outcomes.

• Journal of Microbiology and Biotechnology
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• 제28권9호
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• pp.1413-1425
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• 2018

Shiga toxins (Stxs) are the main virulence factors expressed by the pathogenic Stx-producing bacteria, namely, Shigella dysenteriae serotype 1 and certain Escherichia coli strains. These bacteria cause widespread outbreaks of bloody diarrhea (hemorrhagic colitis) that in severe cases can progress to life-threatening systemic complications, including hemolytic uremic syndrome (HUS) characterized by the acute onset of microangiopathic hemolytic anemia and kidney dysfunction. Shiga toxicosis has a distinct pathogenesis and animal models of Stx-associated HUS have allowed us to investigate this. Since these models will also be useful for developing effective countermeasures to Stx-associated HUS, it is important to have clinically relevant animal models of this disease. Multiple studies over the last few decades have shown that mice injected with purified Stxs develop some of the pathophysiological features seen in HUS patients infected with the Stx-producing bacteria. These features are also efficiently recapitulated in a non-human primate model (baboons). In addition, rats, calves, chicks, piglets, and rabbits have been used as models to study symptoms of HUS that are characteristic of each animal. These models have been very useful for testing hypotheses about how Stx induces HUS and its neurological sequelae. In this review, we describe in detail the current knowledge about the most well-studied in vivo models of Stx-induced HUS; namely, those in mice, piglets, non-human primates, and rabbits. The aim of this review is to show how each human clinical outcome-mimicking animal model can serve as an experimental tool to promote our understanding of Stx-induced pathogenesis.

• 동의생리병리학회지
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• 제30권6호
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• pp.447-451
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• 2016

In this study, Albizziae Cortex extracts (ACE) have potent effects on adipogenesis and on lipolysis in OP9 cells. There was no cytotoxicity while cells were treated with ACE in designated time intervals, unaffected by various concentrations. In the cells with ACE-treated, increases in fat storage were inhibited, and also confirmed by Oil red O. To understand the underlying mechanism at the molecular level, the effects of ACE were examined on the expression of the genes involved in adipogenesis by using real-time PCR. In this cell model, the mRNA level of adipogenic genes such as peroxisome-proliferator-activated receptors gamma ($PPAR{\gamma}$) and CAAAT/enhancer binding protein alpha ($C/EBP{\alpha}$) were decreased by ACE treatment, comparing with those of control group. Collectively, our data suggest that ACE may have great potential as a novel anti-obesity agent.

• 동의생리병리학회지
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• 제31권6호
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• pp.362-366
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• 2017

In this study, Banhasasim-tang extracts (BSTE) have an inhibitory effects on cisplatin-induced decrease of body weights in two mouse model. Cisplatin is the most widely used anticancer drug for treatment of various cancer. However, cisplatin treatment to cancer patients leads to many side effects such as nausea, vomiting and body weight decrease. BSTE has been used to decrease digestive disorders in South Korea. We hypothesize that BSTE improve the cisplatin-induced side effects in mouse models. We found that pre- and co-administration of BSTE inhibited decreases of body weights and food intake by cisplatin in mouse models. But BSTE had no synergistic effects for tumor shrinkage by cisplatin in xenograft model. Collectively, our data suggest that BSTE have great potential as a agent for having decrease effects on side effects by cisplatin in cancer patients.

• Restorative Dentistry and Endodontics
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• 제27권5호
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• pp.543-551
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• 2002

Nitric oxide (NO) is a small molecule (mol. wt. 30 Da) and oxidative free radical. It is uncharged and can therefore diffuse freely within and between cells across membrane. Such characteristics make it a biologically important messenger in physiologic processes such as neurotransmission and the control of vascular tone. NO is also highly toxic and is known to acts as a mediator of cytotoxicity during host defense. NO is synthesized by nitric oxide synthase (NOS) through L-arginine/nitric oxide pathway which is a dioxygenation process. NO synthesis involves several participants, three co-substrates, five electrons, five co-factors and two prosthetic groups. Under normal condition, low levels of NO are synthesized by type I and III NOS for a short period of time and mediates many physiologic processes. Under condition of oxidant stress, high levels of NO are synthesized by type II NOS and inhibits a variety of metabolic processes and can also cause direct damage to DNA. Such interaction result in cytostasis, energy depletion and ultimately cell death. NO has the potential to interact with a variety of intercellular targets producing diverse array of metabolic effects. It is known that NO is involved in hemodynamic regulation, neurogenic inflammation, re-innervation, management of dentin hypersensitivity on teeth. Under basal condition of pulpal blood flow, NO provides constant vasodilator tone acting against sympathetic vasoconstriction. Substance P, a well known vasodilator, was reported to be mediated partly by NO, while calcitonin-gene related peptide has provided no evidence of its relation with NO. This review describes the roles of NO in dental pulp in addition to the known general roles of it.

• Journal of Microbiology and Biotechnology
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• 제28권10호
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• pp.1683-1690
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• 2018

Accurate and rapid diagnosis of influenza infection is essential to enable early antiviral treatment and reduce the mortality associated with seasonal and epidemic infections. Immunochromatography is one of the most common methods used for the diagnosis of seasonal human influenza; however, it is less effective in diagnosing pandemic influenza virus. Currently, rapid diagnostic kits for pandemic influenza virus rely on the detection of nucleoprotein (NP) or hemagglutinin (HA). NP detection shows higher specificity and is more sensitive than HA detection. In this study, we time-dependently screened expression conditions, and herein report optimal conditions for the expression of recombinant nucleoprotein (rNP), which was 48 h after infection. In addition, we report the use of the expressed rNP in a rapid influenza diagnostic test (SGT i-flex Influenza A&B Test). We constructed expression vectors that synthesized rNP (antigen) of influenza A and B in insect cells (Sf9 cells), employed the purified rNP to the immunoassay test kit, and clearly distinguished NPs of influenza A and influenza B using this rapid influenza diagnostic kit. This approach may improve the development of rapid test kits for influenza using NP.

• Journal of Microbiology and Biotechnology
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• 제22권7호
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• pp.990-999
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• 2012

The microbial biosynthesis of fatty acid of lipid metabolism, which can be used as precursors for the production of fuels of chemicals from renewable carbon sources, has attracted significant attention in recent years. The regulation of fatty acid biosynthesis pathways has been mainly studied in a model prokaryote, Escherichia coli. During the recent period, global regulation of fatty acid metabolic pathways has been demonstrated in another model prokaryote, Bacillus subtilis, as well as in Streptococcus pneumonia. The goal of this study was to increase the production of long-chain fatty acids by developing recombinant E. coli strains that were improved by an elongation cycle of fatty acid synthesis (FAS). The fabB, fabG, fabZ, and fabI genes, all homologous of E. coli, were induced to improve the enzymatic activities for the purpose of overexpressing components of the elongation cycle in the FAS pathway through metabolic engineering. The ${\beta}$-oxoacyl-ACP synthase enzyme catalyzed the addition of acyl-ACP to malonyl-ACP to generate ${\beta}$-oxoacyl-ACP. The enzyme encoded by the fabG gene converted ${\beta}$-oxoacyl-ACP to ${\beta}$-hydroxyacyl-ACP, the fabZ catalyzed the dehydration of ${\beta}$-3-hydroxyacyl-ACP to trans-2-acyl-ACP, and the fabI gene converted trans-2-acyl-ACP to acyl-ACP for long-chain fatty acids. In vivo productivity of total lipids and fatty acids was analyzed to confirm the changes and effects of the inserted genes in E. coli. As a result, lipid was increased 2.16-fold higher and hexadecanoic acid was produced 2.77-fold higher in E. coli JES1030, one of the developed recombinants through this study, than those from the wild-type E. coli.