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Ju Hyein,Yun HongDuck,Kim YongHwan,Nam Yun Ji,Lee Seungun,Lee Jinwon,Jeong Seon Min,Heo Jinbeom,Kwon Hyungu,Cho You Sook,Jeong Gowun,Ryu Chae-Min,Shin Dong-Myung 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
Glutathione (GSH), an abundant nonprotein thiol antioxidant, participates in several biological processes and determines the functionality of stem cells. A detailed understanding of the molecular network mediating GSH dynamics is still lacking. Here, we show that activating transcription factor-2 (ATF2), a cAMP-response element binding protein (CREB), plays a crucial role in maintaining the level and activity of GSH in human mesenchymal stem cells (MSCs) by crosstalking with nuclear factor erythroid-2 like-2 (NRF2), a well-known master regulator of cellular redox homeostasis. Priming with ascorbic acid 2-glucoside (AA2G), a stable vitamin C derivative, increased the expression and activity of ATF2 in MSCs derived from human embryonic stem cells and umbilical cord. Subsequently, activated ATF2 crosstalked with the CREB1-NRF2 pathway to preserve the GSH dynamics of MSCs through the induction of genes involved in GSH synthesis (GCLC and GCLM) and redox cycling (GSR and PRDX1). Accordingly, shRNA-mediated silencing of ATF2 significantly impaired the self-renewal, migratory, proangiogenic, and anti-inflammatory capacities of MSCs, and these defects were rescued by supplementation of the cells with GSH. In addition, silencing ATF2 attenuated the ability of MSCs to alleviate airway inflammatory responses in an ovalbumin-induced mouse model of allergic asthma. Consistently, activation of ATF2 by overexpression or the AA2G-based priming procedure enhanced the core functions of MSCs, improving the in vivo therapeutic efficacy of MSCs for treating asthma. Collectively, our findings suggest that ATF2 is a novel modulator of GSH dynamics that determines the core functionality and therapeutic potency of MSCs used to treat allergic asthma.
( Dae Yun Seo ),( Jun Hyun Bae ),( Didi Zhang ),( Wook Song ),( Hyo-bum Kwak ),( Jun-won Heo ),( Su-jeen Jung ),( Hyeong Rok Yun ),( Tae Nyun Kim ),( Sang Ho Lee ),( Amy Hyein Kim ),( Dae Hoon Jeong ) 생화학분자생물학회 2021 BMB Reports Vol.54 No.11
Cisplatin is widely known as an anti-cancer drug. However, the effects of cisplatin on mitochondrial function and autophagy-related proteins levels in the skeletal muscle are unclear. The purpose of this study was to investigate the effect of different doses of cisplatin on mitochondrial function and autophagy-related protein levels in the skeletal muscle of rats. Eight-week-old male Wistar rats (n = 24) were assigned to one of three groups; the first group was administered a saline placebo (CON, n = 10), and the second and third groups were given 0.1 mg/kg body weight (BW) (n = 6), and 0.5 mg/kg BW (n = 8) of cisplatin, respectively. The group that had been administered 0.5 mg cisplatin exhibited a reduced BW, skeletal muscle tissue weight, and mitochondrial function and upregulated levels of autophagy-related proteins, including LC3II, Beclin 1, and BNIP3. Moreover, this group had a high LC3 II/I ratio in the skeletal muscle; i.e., the administration of a high dose of cisplatin decreased the muscle mass and mitochondrial function and increased the levels of autophagy-related proteins. These results, thus, suggest that reducing mitochondrial dysfunction and autophagy pathways may be important for preventing skeletal muscle atrophy following cisplatin administration. [BMB Reports 2021; 54(11): 575-580]
PGA2 induces the expression of HO-1 by activating p53 in HCT116 cells
Hyein Lee,Sang-Sun Lee,Ji-Young Park,Yun-Jeong Choe,이선영,Ho-Shik Kim,H.-S. Kim 대한독성 유전단백체 학회 2017 Molecular & cellular toxicology Vol.13 No.2
Prostaglandin (PG) A2 which is a cytotoxic PG, was reported to induce the expression of heme oxygenase (HO)-1 via activation of p38MAPK to keep U2OS cells from cell cycle arrest in G2M phase. The expression of HO-1 is primarily regulated at the level of transcription. But the transcription factors that are responsible for PGA2-induced HO-1 expression were not clarified yet. Here, we report that PGA2-induced transcription of HO-1 is mediated by p53, a tumor suppressive transcription factor. In HCT116 cells, PGA2 treatment led to the phosphorylation of p53 and an increase of p21WAF1 transcription as well as the activation of HO-1 transcription. Knocking p53 down via RNA interference or inhibiting the p53’s transcriptional activity by pifithrin-α treatment led to suppression of the increase in the level of both HO-1 expression and activity of HO-1 promoter. Pretreatment of NU- 7441, a chemical inhibitor of DNA-activated protein kinase (DNA-PK), prevented both the PGA2-induced phosphorylation of p53 and an increase of HO-1 transcription. In addition, N-acetyl-l-cysteine, a scavenger of reactive oxygen species (ROS), also mimicked the effect of NU-7441 on the PGA2-induced activation of p53 and HO-1 transcription. Collectively, these results suggest that PGA2 induces the expression of HO-1 via activation of p53, which is mediated by the ROSDNA- PK pathway.
Yun Shin Young,Rim John Hoon,Kang Hyein,Lee Sang-Guk,Lim Jong-Baeck 대한진단검사의학회 2023 Annals of Laboratory Medicine Vol.43 No.3
Background: Despite the superiority of non-HDL cholesterol (non-HDL-C) and apolipoprotein B (ApoB) as lipid markers for atherosclerotic cardiovascular disease (ASCVD), these are only suitable as secondary markers. We compared LDL cholesterol (LDL-C), non-HDL-C, and ApoB concentrations with respect to the occurrence of cardiovascular disease in adults enrolled in the Korean Genome and Epidemiology Study (KoGES). Methods: We used information on age; sex; medical history; family history of ASCVD; current lipid-lowering therapy; current smoking status; and creatinine, total cholesterol, HDL-C, LDL-C, triglyceride, and ApoB concentrations from 5,872 KoGES participants without ASCVD. New ASCVD development was monitored during the 8-year follow-up period. Adjusted hazard ratios (aHRs) for ASCVD of LDL-C, non-HDL-C, and ApoB concentrations were calculated based on the multivariate Cox regression analyses. The participants were also grouped as low and high according to the median values for each lipid marker, and calculated aHRs of each group combined by two lipid makers. Results: ApoB showed the highest aHR per 1-SD for ASCVD (1.26; 95% confidence interval [CI], 1.11–1.43), followed by non-HDL-C (1.25; 95% CI, 1.11–1.41) and LDL-C (1.20; 95% CI, 1.06–1.37). The group with low LDL-C and high ApoB concentrations had a significantly higher aHR for ASCVD (1.61; 95% CI, 1.05–2.48) compared to the reference group values (low LDL-C and low ApoB concentrations). The aHR for the group with high LDL-C and low ApoB concentrations was not significant (1.30; 95% CI, 0.79–2.16). Conclusions: ApoB, non-HDL-C, and LDL-C are independent risk factors for ASCVD. Increases in the aHR per 1-SD for ASCVD were more strongly affected by ApoB, followed by non-HDL-C and LDL-C. Participants with low LDL-C and high ApoB concentrations showed increased ASCVD risk. For individuals with ASCVD risk factors, even those presenting normal LDL-C concentrations, measuring Apo
Hyein Ha,Jinhwi Cho,Ja Yeon Lee,Buyong Yun,Jihoon Lee,Min Chul Suh 한국공업화학회 2020 Journal of Industrial and Engineering Chemistry Vol.87 No.-
A series of new asymmetric anthracene derivatives have been successfully synthesized for use in the lightemitting layer of solution processed bluefluorescent organic light emitting diodes (OLEDs), which couldbe used both as host and dopant. Especially, new synthetic bluefluorescent materials with anthracenemoieties without any alkyl chains showed high solubility in common organic solvents probably due totheir severely twisted internal structures. They also show moderately high thermal stability due to theirrigid internal core units. With those novel soluble bluefluorescent materials, we created moderatelyefficient solution-processedfluorescent OLEDs. And a new anthracene derivative [9-(9,10-di(naphthalen-2-yl)anthracen-2-yl)-9H-carbazole (DN-2-CzA)] as a host material exhibited moderately high efficiencyand external quantum efficiency of up to 3.2 cd/A and 1.6%, respectively, when we utilized 4,40-bis[4-(diphenylamino)styryl]biphenyl as a dopant. Meanwhile, the [N-(naphthalen-1-yl)-9,10-di(naphthalen-2-yl)-N-phenylanthra-cen-2-amine (DN-2-NPAA)] as a dopant material showed pretty good deviceperformance, up to 5.2 cd/A and 2.2% (EQE), when we utilized 2-tert-butyl-9,10-di(naphth-2-yl)anthracene as a host.
PGA2-induced HO-1 attenuates G2M arrest by modulating GADD45α expression
Yun-Jeong Choe,고경원,Hyein Lee,이선영,Byung-Chul Kim,Ho-Shik Kim,Ho-Shik Kim 대한독성 유전단백체 학회 2015 Molecular & cellular toxicology Vol.11 No.4
Prostaglandin (PG) A2, a cyclopentenone PG, arrested the growth of U2OS cells in the G2M phase. While inducing G2M arrest, PGA2 increased the expression of heme oxygenase-1 (HO-1) at the level of transcription along with the accumulation of ROS and the activation of MAPKs including JNK, p38MAPK, and ERK1/2. Among the MAPKs, the inhibition of p38MAPK by a specific chemical inhibitor SB203580, or by RNA interference, but not JNK or ERK1/2, attenuated the PGA2-induced transcription of HO-1. Nacetylcysteine (NAC), a ROS scavenger, prevented PGA2-induced G2M arrest, p38MAPK activation and transcriptional induction of HO-1. PGA2 also stimulated GADD45α expression at the level of transcription, and the knockdown of GADD45α repressed PGA2- induced G2M arrest. Finally, the knockdown of the HO-1 protein elevated PGA2-induced GADD45α expression as well as G2M arrest. Collectively, these results suggest that PGA2 causes an increase in ROS accumulation which initiates both HO-1 transcription via p38MAPK, and G2M arrest via GADD45α transcription, and HO-1 attenuates G2M arrest by modulating the expression of GADD45α.
기계 학습을 위한 데이터 품질 향상 과정을 지원하는 시각적 분석 시스템
홍혜인(Hyein Hong),유상봉(Sangbong Yoo),김지수(Jisue Kim),서성범(Seongbum Seo),장윤(Yun Jang) 한국HCI학회 2023 한국HCI학회 학술대회 Vol.2023 No.2
기계 학습 모델은 데이터에 숨겨진 정보들을 마이닝하기 위해 사용된다. 기계 학습 모델의 성능은 알고리즘과 데이터의 품질에 영향을 받는다. 그러나 성능을 측정하며 모델을 수정하는 작업은 비효율적이며, 품질이 낮은 데이터는 모델의 편향된 학습을 야기한다. 따라서 데이터 품질을 향상시키는 작업은 중요하다. 기존에 데이터 품질 향상 과정을 지원하는 시각적 분석시스템들이 제안되었다. 그러나 제안된 연구들은 사용자가 기계 학습을 위한 종합적인 데이터 품질향상 방법들을 고려하고, 적합한 데이터 품질 향상 과정을 판별하기 어렵다. 이 논문에서 우리는 기계학습 모델에 사용되기 위해 데이터 품질을 관리하는 새로운 시각적 분석 시스템을 제안한다.