Blockade of RAGE ameliorates elastase-induced emphysema development and progression <i>via</i> RAGE-DAMP signaling

Lee, Hanbyeol,Park, Jeong-Ran,Kim, Woo Jin,Sundar, Isaac K.,Rahman, Irfan,Park, Sung-Min,Yang, Se-Ran The Federation of American Societies for Experimen 2017 The FASEB Journal Vol.31 No.5

<P>The receptor for advanced glycan end products (RAGE) has been identified as a susceptibility gene for chronic obstructive pulmonary disease (COPD) in genome-wide association studies (GWASs). However, less is known about how RAGE is involved in the pathogenesis of COPD. To determine the molecular mechanism by which RAGE influences COPD in experimental COPD models, we investigated the efficacy of the RAGE-specific antagonist FPS-ZM1 administration in in vivo and in vitro COPD models. We injected elastase intratracheally and the RAGE antagonist FPS-ZM1 in mice, and the infiltrated inflammatory cells and cytokines were assessed by ELISA. Cellular expression of RAGE was determined in protein, serum, and bronchoalveolar lavage fluid of mice and lungs and serum of human donors and patients with COPD. Downstream damage-associated molecular pattern (DAMP) pathway activation in vivo and in vitro and in patients with COPD was assessed by immunofluorescence staining, Western blot analysis, and ELISA. The expression of membrane RAGE in initiating the inflammatory response and of soluble RAGE acting as a decoy were associated with up-regulation of the DAMP-related signaling pathway via Nrf2. FPS-ZM1 administration significantly reversed emphysema in the lung of mice. Moreover, FPS-ZM1 treatment significantly reduced lung inflammation in Nrf2(+/+) , but not in Nrf2(-/-) mice. Thus, our data indicate for the first time that RAGE inhibition has an essential protective role in COPD. Our observation of RAGE inhibition provided novel insight into its potential as a therapeutic target in emphysema/COPD.-Lee, H., Park, J.-R., Kim, W. J., Sundar, I. K., Rahman, I., Park, S.-M., Yang. S.-R. Blockade of RAGE ameliorates elastase-induced emphysema development and progression via RAGE-DAMP signaling.</P>

Differential Expressions of Gap Junction Proteins during Differentiation of Rat Neuronal Stem Cells

Yang, Se-Ran,Cho, Sung-Dae,Ahn, Nam-Shik,Jung, Ji-Won,Park, Joon-Suk,Tiep, Nguyen Ba,Park, Ki-Su,Hong, In-Sun,Jo, Eun-Hye,Seo, Min-Seo,Yoon, Byong-Su,Lee, Yong-Soon,Kang, Kyung-Sun Korean Environmental Mutagen Society 2003 한국환경성돌연변이·발암원학회지 Vol.23 No.1

Gap junctional intercellular communication (GJIC) plays a key role during development, process of tissue differentiation, and in maintenance of adult tissue homeostasis. Neural stem cells leading to formation of cell clusters termed 'neurospheres', can differentiate into neurons, oligodendrocytes, and astrocytes. We investigated the expression levels and distribution of connexin43 (Cx43) and connexin32 (Cx32), abundant gap junctional protein in neural cells and in neurospheres isolated from rat fetus embryonic day (ED) 17. During differentiation of neurospheres, expression of Cx43 and 32 were increased time-dependently within 72 h, and then decreased at 7 day in western blot analysis. TPA-induced inhibition of GJIC was confirmed by decreased fluorescence by SL/DT assay, and induced hyperphosphorylation of Cx43 while no changes in Cx32 levels in western blot assay. Our results indicate that GJIC may be a crucial role in the differentiation of neuronal stem cell. And this GJIC can be inhibited by TPA through the hyperphosphorylation of Cx43.

Differential Expressions of Gap Junction Proteins during Differentiation of Rat Neuronal Stem Cells

Se-Ran Yang,Sung-Dae Cho,Nam-Shik Ahn,Ji-Won Jung,Joon-Suk Park,Nguyen Ba Tiep,Ki-Su Park,In-Sun Hong,Eun-Hye Jo,Min-Su Seo,Byong-Su Yoon,Yong-Soon Lee,Kyung-Sun Kang 한국환경성돌연변이발암원학회 2003 한국환경성돌연변이·발암원학회지 Vol.23 No.1

Gap junctional intercellular communication (GJIC) plays a key role during development, process of tissue differentiation, and in maintenance of adult tissue homeostasis. Neural stem cells leading to formation of cell clusters termed “neurospheres”, can differentiate into neurons, oligodendrocytes, and astrocytes. We investigated the expression levels and distribution of connexin43 (Cx43) and connexin32 (Cx32), abundant gap junctional protein in neural cells and in neurospheres isolated from rat fetus embryonic day (ED) 17. During differentiation of neurospheres, expression of Cx43 and 32 were increased time-dependently within 72 h, and then decreased at 7 day in western blot analysis. TPA-induced inhibition<br/> of GJIC was confirmed by decreased fluorescence by SL/DT assay, and induced hyperphosphorylation of Cx43 while no changes in Cx32 levels in western blot assay. Our results indicate that GJIC may be a crucial role in the differentiation of neuronal stem cell. And this GJIC can be inhibited by TPA through the hyperphosphorylation of Cx43.

Effect of coenzyme Q10 via nitric oxide production and growth arrest of human colon cancer HCT116 cells

Se-Ran Yang,Soojin Jang,Jooyeon Lee,Se Min Ryu,Hanbyeol Lee,Jeong-Ran Park,Aera Jang,Dongwook Kim,Hyejin Kim 한국예방수의학회(구 한국수의공중보건학회) 2017 예방수의학회지 Vol.42 No.2

Colorectal cancer is a major cause of morbidity and mortality that accounts for over 9% of all incidences of cancer. Additionally, colorectal cancer is widely recognized as an environmental disease related to ill-defined cultural, social and lifestyle factors including physical activity, obesity, cigarette smoking and heavy alcohol consumption. Accordingly, natural phytochemicals and extracts have attracted attention because of their beneficial biological effects. Coenzyme Q10 (CoQ10) is a common supplementary medicine applied to increase bioenergetic capacity in various diseases. Therefore, in this study, we investigated whether CoQ10 treatment has any inhibitory effects and its related cellular mechanisms in human colon cancer HCT116 cells. A MTT assay revealed that CoQ10 slightly decreased the proliferation of HCT116 cells; however, glutathione- and superoxide dismutase- activity were unchanged in response to CoQ10 treatment. A DCF-DA assay revealed that CoQ10 slightly increased ROS release of HCT116 cells. However, in a nitric oxide (NO) assay, CoQ10 significantly increased NO production in a dose-dependent manner. The results of western blot analysis revealed that the protein levels of Bax, p21 and p53 were increased, whereas the protein level of Bcl2 was decreased suggesting that the CoQ10-mediated inhibitory mechanism is associated with apoptotic signaling. Taken together, our findings indicate that CoQ10 has an inhibitory effect on the growth of colon cancer cells via NO production that is associated with regulation of factors involved in apoptotic signaling including Bax, Bcl2, p21 and p53.

Screening of Korean Medicinal Herbs for Hormonal Activities using Recombinant Yeast Assay and MCF-7 Human Breast Cancer Cells

Yang, Se-Ran,Hong, Hee-Do,Cho, Sung-Dae,Ahn, Nam-Shik,Jung, Ji-Won,Park, Joon-Suk,Jo, Eun-Hye,Hwang, Jae-Woong,Sun-bo,Park, Jung-Ran,Lee, Seong-Hun,Jung, Ji-Youn,Choi, Changsun,Kang, Kyung-Sun,Lee, Yo 한국식품위생안전성학회 2005 한국식품위생안전성학회지 Vol.20 No.1

약용식물내 에스트로겐성과 항-에스트로겐성을 조사하고 항암인자를 발견하기 위하여, 본연구는 에탄올추출로 제조된 9종류의 한국산 약용식물에 대하여 재조합효모와 MCF-7 사람유방암세포주를 이용하여 스크리닝하고 비교하였다. 재조합효모를 이용한 실험결과, 7종류의 약용식물에서 에스트로겐성이 나타났고, 4종류에서 안드로겐성이 나타났다. 또한 MCF-7 사람유방암세포주를 이용한 실험결과, 8종류의 추출물이 MCF-7 세포의 성장을 억제하는 것으로 확인되었으며 비스페놀 A와 동시 처치한 경우에도 유의적으로 억제하는 것으로 나타났다. 또한 Clyeyrrhiza uralensis, Cassia tora, Syringa velutina, Zingiber officinale, Malva verticillata, Panax ginseng C.A. Meyer는 식물성 에스트로겐으로서 에스트로겐에 양성인 사람유방암세포의 증식을 유의적으로 억제시티는 흥미로운 결과가 제시되었다. 따라서 이번 연구는 한국산 약용식물이 식물성 에스트로겐과 항암인자로서 이용될 수 있으며, 에스트로겐의 활성을 조사하는데 유용하게 이용될 수 있을 것으로 사료된다. To investigate whether there are estrogenic and anti-estrogenic activities in various medicinal herbs and discover prominent chemo-preventive agents, eye screened and compared the ethanol extracts of 9 plants through the recombinant yeast assay and MCF-7 human breast cancer cell assay. In recombinant yeast assay. seven medicinal herbs showed estrogenicity, and tour extracts showed androgenecity. In MCF-7 proliferation assay. the growth of MCF-7 cells was inhibited by eight extracts before and even alter co-treatment with bisphenol A. It is interesting that the extracts of Glyeyrrhiza uralensis, Cassia tora, Syringa velutina, Zingiber officinale, Malva verticillata, and Ponax ginseng C.A. Meyer exhibited inhibitory effects as phytoestrogens in estrogen-responsive human breast cancer cells. This study suggests that some Korean medicinal herbs might be considered as phytoestrooens and be useful to further analyze those plants which contain the estrogenic effect in order to identify the active principles.

NPC1 Gene Deficiency Leads to Lack of Neural Stem Cell Self-Renewal and Abnormal Differentiation Through Activation of p38 Mitogen-Activated Protein Kinase Signaling

Yang, Se-Ran,Kim, Sun-Jung,Byun, Kyoung-Hee,Hutchinson, Brian,Lee, Bong-Hee,Michikawa, Makoto,Lee, Yong-Soon,Kang, Kyung-Sun Wiley (John WileySons) 2006 Stem cells Vol.24 No.2

<P>Neural stem cells (NSCs) are capable of giving rise to neurons, glia, and astrocytes. Although self-renewal and differentiation in NSCs are regulated by many genes, such as Notch and Numb, little is known about the role of defective genes on the self-renewal and differentiation of NSCs from developing brain. The Niemann-Pick type C1 (NPC1) disease is a neurodegenerative disease caused by a mutation of the NPC1 gene that affects the function of the NPC1 protein. The ability of NSC self-renewal and differentiation was investigated using a model of NPC1 disease. The NPC1 disorder significantly affected the self-renewal ability of NSCs, as well as the differentiation. NSCs from NPC1-/- mice showed impaired self-renewal ability compared with the NPC1+/+ mice. These alterations were accompanied by the enhanced activity of p38 mitogen-activated protein kinases (MAPKs). Further, the specific p38 MAPK inhibitor SB202190 improved the self-renewal ability of NSCs from NPC-/- mice. This indicated that the NPC1 deficiency can lead to lack of self-renewal and altered differentiation of NSCs mediated by the activation of p38 MAPK, impairing the generation of neurospheres from NPC1-/- Thus, the NPC1 gene may play a crucial role in NSC self-renewal associated with p38 MAPK.</P>

랫드에서 Pueraria mirifica 추출물의 주산기 및 수유기시험

양세란(Se-Ran Yang),조성대(Sung-Dae Cho),조종호(Jong-Ho Cho),김경배(Kyung-Bae Kim),이지해(Ji-Hae Lee),안남식(Nam-Shik Ahn),정지원(Ji-Won Jung),박준석(Joon-Suk Park),이영순(Yang-Soon Lee),강경선(Kyung-Sun Kang) 한국환경성돌연변이발암원학회 2002 한국환경성돌연변이·발암원학회지 Vol.22 No.2

To evaluate the modifying effect of Kwao Kreu, Pueraria mirifica (PM) well-known as a rejuvenating folk medicine from Thailand, peri- and post-natal studies were carried out in rats. PM extract was administered to pregnant Sprague Dawley (SD) rats by oral gavage from gestation 6 (GD 6) to postnatal day 21 (PND 21). The amount of administered in this study was 0.042, 0.42 and 4.2 mg/kg/day, respectively. There were no treatment related changes of dams in deaths, clinical signs, and parturition. Treatment related changes in body weight, food consumption and lactation of dams were not observed. F1 fetuses in external abnormality, physical development, reflex/sensory functions and behavioral development were not found. No adults and F1 fetuses in organ weight was found with the exception of vagina and uterus of F1 fetuses. The results showed that PM extract, up to 4.2 mg, had no adverse effects on the peri- and post-natal development of rats. Therefore, PM extract has no adverse effects on peri- and post-natal development of rats.

Nicotine inhibits the proliferation by upregulation of nitric oxide and increased HDAC1 in mouse neural stem cells

Lee, Hanbyeol,Park, Jeong-Ran,Yang, Jungwon,Kim, Eunjeong,Hong, Seok-Ho,Woo, Heung-Myong,Ryu, Se-Min,Cho, Sung-Joon,Park, Sung-Min,Yang, Se-Ran Springer-Verlag 2014 In vitro cellular & developmental biology Animal Vol.50 No.8

<P>Cigarette smoking (CS) is considered one of the major risk factors to cause neurodegenerative disorders. Nicotine is the main chemical in CS which is responsible for dysfunction of the brain as a neuroteratogen. Also, nicotine dependency is a real mental illness and disease. Recently, chronic nicotine exposure has been shown to cause oxidative/nitrosative stress leading to a deleterious condition to cellular death in different brain regions. However, little is known about the effects of nicotine on mouse neural stem cells (mNSCs). The aim of this study is to investigate the effects of nicotine on mNSCs and elucidate underlying mechanisms involved in expression of a diversity of genes regulated by nicotine. When mNSCs were isolated from the whole brain of embryonic day 16 mice treated with nicotine at vehicle, 100, 400, and 800?μM for 5?d, nicotine significantly decreased the number and size of neurospheres. In immunocytochemistry, nicotine-exposed mNSCs expressing nestin showed the shortened filaments and condensed nuclei. In RT-PCR, messenger RNA (mRNA) levels of proliferating cell nuclear antigen (PCNA) and sirtuin1 (SIRT1) were significantly decreased, while the production of nitric oxide and mRNA levels of cyclooxygenase2 (COX-2), tumor necrosis factor-alpha TNF-α, and histone deacetylase 1 (HDAC1) were increased in a dose-dependent manner. In addition, sodium butyrate and valproic acid, HDAC inhibitors, partially rescue proliferation of mNSCs via inhibition of HDAC1 expression and NO production. Taken together, these data demonstrate that prolonged exposure of nicotine decreased proliferation of mNSCs by increased NO and inflammatory cytokine through increased HDAC1. Furthermore, this study could help in the development of a therapy for nicotine-induced neurodegenerative disorder and drug abuse.</P>

단고추 종류와 데침처리에 따른 영양성분 변화 및 잔존율 비교

김홍균,황진봉,김세나,최용민,김소민,한혜경,양미란,김행란,Kim, Honggyun,Hwang, Jin Bong,Kim, Se Na,Choi, Youngmin,Kim, So-Min,Han, Hye-Kyung,Yang, Mi-Ran,Kim, Haeng Ran 한국식품조리과학회 2016 한국식품조리과학회지 Vol.32 No.4

Purpose: To provide the nutritional information of sweet peppers, we have evaluated changes of nutrient content and retention rates by different sweet pepper types and blanching method. Methods: Four types of raw and blanched ($100^{\circ}C$, 30 sec) sweet peppers were prepared and their weight, nutrient content (3 water soluble vitamins, 10 minerals) and retention rates were analyzed. Results: The weight of blanched sweet peppers was decreased than that of raw sweet peppers. From the results of the two-way analysis, the type of sweet pepper had a greater influence than blanching method used on the thiamine, riboflavin, folate and vitamin C contents (but not niacin) (p<0.05). Red pimento contained the most thiamine (0.1 mg/100 g), riboflavin (0.16 mg/100 g), folate ($47.89{\mu}g/100g$) and total niacin (0.11 mg/100 g). Red paprika contained high levels of riboflavin (0.15 mg/100 g) and folate ($44.96{\mu}g/100g$). Orange paprika contained the highest vitamin C content (116.29 mg/100 g). In addition, the mineral content, with the exception of Se, was strongly influenced by the type of sweet pepper rather than the blanching method (p<0.001). The K content of sweet peppers was higher than other minerals. Overall, after blanching, high retention rates (over 70%) were observed in all types of sweet peppers. However, the retention rates of thiamin, vitamin C and Se showed lower levels (less than 70%). Conclusion: The vitamin and mineral contents depends more on the type of sweet pepper; although vitamin and mineral (except Se) contents showed some changes after blanching. Our results can be utilized to determine the effects of cooking processes on nutritional information.

Simple and Novel Assay of the Host-Guest Complexation of Homocysteine with Cucurbit[7]uril

( Se-ho Park ),( Jae-yeul Lee ),( Hyun-nam Cho ),( Kyoung-ran Kim ),( Seun-ah Yang ),( Hee-joon Kim ),( Kwang-hwan Jhee ) 한국미생물 · 생명공학회 2019 Journal of microbiology and biotechnology Vol.29 No.1

This paper introduces three ways to determine host-guest complexation of cucurbit[7]uril (CB[7]) with homocysteine (Hcy). After preincubating Hcy and cysteine (Cys) with CB[7], Ellman’s reagent (DTNB) was used to detect Hcy and Cys. Only Cys reacted with DTNB and Hcy gave a retarded color change. This suggests that the -SH group of Hcy is buried inside CB[7]. Human cystathionine γ-lyase (hCGL) decreased the level of Hcy degradation after preincubating Hcy and CB[7]. These results suggest that the amount of free Hcy available was decreased by the formation of a Hcy-CB[7] complex. The immunological signal of anti-Hcy monoclonal antibody was decreased significantly by preincubating CB[7] with Hcy. The ELISA results also show that ethanethiol group (-CH2CH2SH) of Hcy, which is an epitope of anti-Hcy monoclonal antibody, was blocked by the cavity in CB[7]. Overall, CB[7] can act as a host by binding selectively with Hcy, but not Cys. The calculated half-complexation formation concentration of CB[7] was 58.2 nmol using Ellman’s protocol, 97.9 nmol using hCGL assay and 87.7 nmol using monoclonal antibody. The differing binding abilities of Hcy and Cys towards the CB[7] host may offer a simple and useful method for determining the Hcy concentration in plasma or serum.