Morin exerts cytoprotective effects against oxidative stress in C2C12 myoblasts via the upregulation of Nrf2-dependent HO-1 expression and the activation of the ERK pathway

Lee, Moon Hee,Han, Min Ho,Lee, Dae-Sung,Park, Cheol,Hong, Su-Hyun,Kim, Gi-Young,Hong, Sang Hoon,Song, Kyoung Seob,Choi, Il-Whan,Cha, Hee-Jae,Choi, Yung Hyun UNKNOWN 2017 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.39 No.2

<P>In the present study, we investigated the cytoprotective efficacy of morin, a natural flavonoid, against oxidative stress and elucidated the underlying mechanisms in C2C12 myoblasts. Our results indicated that morin treatment prior to hydrogen peroxide (H2O2) exposure significantly increased cell viability and prevented the generation of reactive oxygen species. H2O2-induced comet-like DNA formation and gamma H2AX phosphorylation were also markedly suppressed by morin with a parallel inhibition of apoptosis in C2C12 myoblasts, suggesting that morin prevented H2O2-induced cellular DNA damage. Furthermore, morin markedly enhanced the expression of heme oxygenase-1 (HO-1) associated with the induction and phosphorylation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and the inhibition of Kelch-like ECH-associated protein 1 (Keapl) expression. Notably, these events were eliminated by transient transfection with Nrf2-specific small interfering RNA. Additional experiments demonstrated that the activation of the Nrf2/HO-1 pathway by morin was mediated by the extracellular signal-regulated kinase (ERK) signaling cascade. This phenomenon was confirmed with suppressed Nrf2 phosphorylation and consequently diminished HO-1 expression in cells treated with a pharmacological inhibitor of ERK. Collectively, these results demonstrated that morin augments the cellular antioxidant defense capacity through the activation of Nrf2/HO-1 signaling, which involves the activation of the ERK pathway, thereby protecting C2C12 myoblasts from H2O2,-induced oxidative cytotoxicity.</P>

혈액투석 환자의 가성 고칼륨혈증

최창렬,조형도,강태영,이준수,한호,정청일,이동규,유준호,한상웅,김호중 대한신장학회 2001 대한신장학회잡지 Vol.20 No.5

Vascular Protective Role of Samul-Tang in HUVECs: Involvement of Nrf2/HO-1 and NO

Choi, Eun Sik,Lee, Yun Jung,Seo, Chang Seob,Yoon, Jung Joo,Han, Byung Hyuk,Park, Min Cheol,Kang, Dae Gill,Lee, Ho Sub Hindawi Publishing Corporation 2016 Evidence-based Complementary and Alternative Medic Vol.2016 No.-

<P>Samul-Tang (Si-Wu-Tang, SMT), composed of four medicinal herbs, is a well-known herbal formula treating hematological disorder or gynecologic disease. However, vascular protective effects of SMT and its molecular mechanisms on the vascular endothelium, known as the central spot of vascular inflammatory process, are not reported. The aim of this study was to investigate vascular protective effects of SMT water extract in human umbilical vein endothelial cells (HUVECs). Water extract of SMT was prepared and identified by HPLC-PDA analysis. Expression of cell adhesion molecules (CAMs) and heme oxygenase-1 (HO-1) and translocation of nuclear factor-kappa B (NF-<I>κ</I>B) and nuclear factor-erythroid 2-related factor 2 (Nrf2) were determined by western blot. Nuclear localization of NF-<I>κ</I>B and Nrf2 was visualized by immunofluorescence and DNA binding activity of NF-<I>κ</I>B was measured. ROS production, HL-60 monocyte adhesion, and intracellular nitric oxide (NO) were also measured using a fluorescent indicator. SMT suppressed NF-<I>κ</I>B translocation and activation as well as expression of CAMs, monocyte adhesion, and ROS production induced by TNF-<I>α</I> in HUVECs. SMT treated HUVECs showed upregulation of HO-1 and NO which are responsible for vascular protective action. Our study suggests that SMT, a traditionally used herbal formula, protects the vascular endothelium from inflammation and might be used as a promising vascular protective drug.</P>

Platycodon grandiflorum root-derived saponins attenuate atopic dermatitis-like skin lesions via suppression of NF-kB and STAT1 and activation of Nrf2/ARE-mediated heme oxygenase-1

( Jae Ho Choi ),( Sun Woo Jin ),( Eun Hee Han ),( Bong Hwan Park ),( Hyung Gyun Kim ),( Tilak Khanal ),( Yong Pil Hwang ),( Minh Truong Do ),( Hyun Sun Lee ),( Young Chul Chung ),( Hee Suk Kim ),( Tae 영남대학교 약품개발연구소 2014 영남대학교 약품개발연구소 연구업적집 Vol.24 No.0

Purpose: The consequences of precipitously rising allergic skin inflammation rates worldwide have accelerated the risk of atopic dermatitis (AD). Natural product-based agents with good efficacy and low risk of side effects offer promising prevention and treatment strategies for inflammation-related diseases. We have already reported that Platycodon grandiflorum root-derived saponins (Changkil saponins, CKS) have many pharmacological effects, including anti-inflammatory and anti-allergic effects, but its influence on AD remains unclear. Therefore, we evaluated the inhibitory effect of CKS, mainly platycodin D, on AD-like skin symptoms in mice and the possible mechanisms in cells. Methods: Mice were sensitized and challenged with 2,4-dinitrochlorobenzene (DNCB). Four weeks after challenge, mice were treated with oral administration of CKS for 4 weeks. In addition, cells were used to evaluate the effect of CKS, mainly platycodin D, on the TARC expression regulated mechanism. Results: CKS attenuated DNCB-induced dermatitis severity, serum levels of IgE and TARC, and mRNA expression of TARC, TNF-α, IFN-γ, IL-4, IL-5, and IL-13 in mice. Histopathological examination showed reduced thickness of the epidermis/dermis and dermal infiltration of inflammatory cells and mast cells in the ears. Moreover, CKS and platycodin D inhibited TNF-α/IFN-γ-induced TARC expression through the suppression of NF-κB and STAT1 and induction of Nrf2/ARE-mediated hemeoxygenase-1 (HO-1) expression in cells. Conclusion: We suggest that CKS and platycodin D inhibited the development of AD-like skin symptoms by regulating cytokine mediators and may be an effective alternative therapy for AD-like skin symptoms.ⓒ2014 Elsevler Gmbh. All rights reserved.

Methanol extract of Myelophycus caespitosus ameliorates oxidative stress‑induced cytotoxicity in C2C12 murine myoblasts via activation of heme oxygenase-1

Cheol Park,Hyun Hwangbo,Han Min Ho,Jin-Woo Jeong,조승목,김기영,황혜진,Yung Hyun Choi 한국수산과학회 2023 Fisheries and Aquatic Sciences Vol.26 No.1

Myelophycus caespitosus, a brown alga belonging to genus Myelophycus, has been traditionally used as a food and medicinal resource in Northeastern Asia. However, few studies have been conducted on its pharmacological activity. In this study, we evaluated whether methanol extract of M. caespitosus (MEMC) could protect against oxidative damage caused by hydrogen peroxide (H2O2) in C2C12 murine myoblasts. Our results revealed that MEMC could suppress H2O2-induced growth inhibition and DNA damage while blocking the production of reactive oxygen species. In H2O2-treated cells, cell cycle progression was halted at the G2/M phase, accompanied by changes in expression of key cell cycle regulators. However, these effects were attenuated by MEMC. In addition, we found that MEMC protected cells from induction of apoptosis associated with mitochondrial impairment caused by H2O2 treatment. Furthermore, MEMC enhanced the phosphorylation of nuclear factor-erythroid-2 related factor 2 (Nrf2) and expression and activity of heme oxygenase-1 (HO-1) in H2O2-treaetd C2C12 myoblasts. However, such anti-apoptotic and cytoprotective effects of MEMC were greatly abolished by HO-1 inhibitor, suggesting that MEMC could increase Nrf2-mediated activity of HO-1 to protect C2C12 myoblasts from oxidative stress.

압축성 코드에서 예조건화 코드로의 이진

한상훈(Sang-Hoon Han),김명호(Myeong-Ho Kim),최정열(Jeong-Yeol Choi) 한국항공우주학회 2007 韓國航空宇宙學會誌 Vol.35 No.3

이차원 범프 유동에 대한 다양한 예조건화 행렬의 수렴 특성을 살펴 Choi와 Merkle의 예조건화 행렬을 선택하여, 압축성 및 예조건화 Roe의 Riemann 해법의 수치 소산항을 수학적으로 비교하였다. 이 결과 코드의 구조는 동일하게 유지한 채, 고유치의 작은 수정만으로 압축성 해법을 예조건화 해법으로 이전할 수 있는 방법을 알 수 있었다. 아울러 점성 유동 영역에서의 안정성 및 정확성을 향상시키기 위하여 von Neumann 안정 조건 및 점성 자코비안을 고려하였으며, 개발된 코드는 표준 검증 문제에 적용하여 검증을 수행하였다. Comprehensive mathematical comparison of numerical dissipation vector was made for a compressible and the preconditioned version Roe's Riemann solvers. Choi and Merkle type preconditioning method was selected from the investigation of the convergence characteristics of the various preconditioning methods for the flows over a two-dimensional bump. The investigation suggests a way of migration from a compressible code to a preconditioning code with a minor changes in Eigenvalues while maintaining the same code structure. Von Neumann stability condition and viscous Jacobian were considered additionally to improve the stability and accuracy for the viscous flow analysis. The developed code was validated through the applications to the standard validation problems.

Antioxidant and cytoprotective effects of morin against hydrogen peroxide-induced oxidative stress are associated with the induction of Nrf-2-mediated HO-1 expression in V79-4 Chinese hamster lung fibroblasts

Lee, Moon Hee,Cha, Hee-Jae,Choi, Eun Ok,Han, Min Ho,Kim, Sung Ok,Kim, Gi-Young,Hong, Su Hyun,Park, Cheol,Moon, Sung-Kwon,Jeong, Soon-Jeong,Jeong, Moon-Jin,Kim, Wun-Jae,Choi, Yung Hyun Spandidos Publications 2017 International journal of molecular medicine Vol.39 No.3

<P>Natural phytochemicals of plant origin, including flavonoids, have been found to be potent antioxidants providing beneficial effects against oxidative stress-related diseases. The present study was carried out to investigate the antioxidant properties of morin, a flavonoid originally isolated from the flowering plants of the Moraceae family. Superoxide dismutase (SOD)-like activity and 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(center dot+)) radical scavenging activity were determined. We also investigated the cytoprotective effects of morin against hydrogen peroxide (H2O2)-induced DNA damage and apoptosis in V79-4 Chinese hamster lung fibroblasts. Our results demonstrated that morin had strong scavenging effects against ABTS' radicals with enhanced SOD activity, which varied in a dose-dependent manner. Morin was found to reduce H2O2-induced intracellular reactive oxygen species generation and nuclear DNA damage, and it recovered cell viability damaged by H2O2 via inhibition of mitochondrial dysfunction-mediated apoptosis. Notably, the treatment of V79-4 cells with morin markedly enhanced the expression of heme oxygenase-1 (HO-1) but not quinone oxidoreductase-1, which was associated with the increased expression and phosphorylation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and the downregulation of Kelch-like ECH-associated protein 1 expression. Based on our findings, we conclude that morin effectively ameliorated oxidative stress-induced DNA damage through intrinsic free radical scavenging activity and activation of the Nrf2/HO-1 pathway.</P>

진피 메탄올 추출물의 활성산소종 생성을 통한 인체 백혈병 세포의 apoptosis 유발

김가희(Ga Hee Kim),이문희(Moon Hee Lee),한민호(Min Ho Han),박철(Cheol Park),홍수현(Su Hyun Hong),최영현(Yung Hyun Choi) 한국생명과학회 2013 생명과학회지 Vol.23 No.8

진피(Citri Pericarpium)의 항암작용 기전 해석을 위하여 U937 백혈병 세포의 apoptosis 유발에 미치는 메탄올추출물(EMCP)의 영향을 조사하였으며, apoptosis 조절에 중요한 몇 가지 유전자들의 발현 및 활성 변화, ROS의 생성 변화를 조사하였다. EMCP 처리에 의한 U937 세포의 증식 억제는 apoptosis 유도와 연관성이 있음을 DAPI 염색을 통한 apoptotic body 출현의 증가 및 Flow cytometry 분석에 의한 Sub-G1기 세포 빈도의 증가로 확인하였다. EMCP 처리에 의한 apoptosis 유도에서 Bax 발현 증가, caspases의 활성 및 PARP의 단편화 등이 동반되었으며, ROS 생성의 증가와 연관성이 있었다. 산화적 손상에 대해 세포나 조직을 보호하는 역할을 하는 것으로 알려진 세포 내 항산화 효소인 HO-1의 발현이 EMCP의 처리에 의해 증가되었으나 ROS 생성 억제제인 NAC의 전처리에 의해 감소된 HO-1의 발현은 전사인자인 Nrf2의 핵으로의 이동 억제와 관련되어 있었다. 이상의 결과에서 EMCP 처리에 의한 U937 세포의 apoptosis 유발에는 ROS 생성의 증가와 pNrf2에 의해 조절되는 HO-1의 발현 증가가 중요한 기전으로 작용한다는 것을 알 수 있었다. 이러한 자료는 진피의 항암기전 해석을 이해하는데 중요한 기초자료로서 활용될 수 있을 것으로 생각된다. Citri Pericarpium is one of the most commonly used traditional herbal medicines in Korea, China, and Japan. Its extracts have many properties including the treatment of indigestion and inflammatory respiratory syndromes such as bronchitis and asthma. However, the underlying molecular mechanisms of anti-cancer activity and molecular targets are not fully understood. In this work, we investigated the anti-proliferative activity of Citri Pericapium (EMCP) methanol extract on reactive oxygen species (ROS) production and the association of these effects with apoptotic cell death using U937 human leukemia cells in vitro. EMCP treatment decreased cell proliferation in a dose-dependent manner following an increase of the sub-G1 phase, the down-regulation of Bax proteins, the activation of caspases, the degradation of poly (ADP-ribose) polymerase proteins (PARP), and the induction of ROS generation. However, the quenching of ROS generation by N-acetyl-L-cysteine administration, a scavenger of ROS, reversed the EMCP-induced apoptosis effects. In addition, heme oxygenase-1 expression also recovered by inhibiting the nuclear translocation of phosphorylated NF-E2-related factor 2. Taken together, our data indicate that ROS are involved as key mediators in the early molecular events in the EMCP-induced apoptotic pathway.

VDSL채널에서 정규화된 MMA 방법을 이용한 블라인드 적응 등화 기법

최성환,김한기,권호열 강원대학교 정보통신연구소 2001 정보통신논문지 Vol.5 No.-

VDSL technology can transmit data at rate of 10-50Mbps over a twisted-pair copper telephone loops. Therefore, one of VDSL core technology is channel equalizer. Because one of the most damaging impairments is linear distortion introduced by cable and RF interference. An adaptive equalizer needs to be trained before reliable transfer of information can be achieved. This can be done in two main ways. One way is to using priori known training sequence. The ocher way is not to using training sequence. This type of initial training of an equalizer is called blind equalization. Blind equalization provide bandwidth-efficient schemes. In this paper we propose dual mode SCS(Soft Constraint Satisfaction)-Multimodulus algorithm derived from the combination of SCS algorithms and decision-directed algorithm. This algorithms provide fast convergence speed and robustness. Using MATLAB, we investigate the performance of dual made SCS-MMA over VDSL test loops.

소양호 지류하천의 비점오염원 유출특성에 관한 연구

최한규,최창호,박수진 江原大學校 産業技術硏究所 2009 産業技術硏究 Vol.29 No.B

This study selected Naerin Stream, Inbuk Stream and Buk Stream, branch rivers of Soyang Dam, also area of highland agriculture as test sites and measured flow and water quality, particularly eutrophication factors (BOD, COD, T-N, and T-P) in precipitation season and non precipitation season for a year, 2008. Based on the result, the study examined the change in water quality in relation to flow, and created flow discharged - pollution loads regression line by estimating pollution loads flowed from each branch river. And the study calculated annual pollution discharge loads for unit area and proposed regression equation on it by using regression analysis.