Prostaglandin A₂-induced Apoptosis is Not Inhibited by Heme Oygenase-1 in U2OS Cells

Kyoung-Won Ko(고경원),Sun-Young Lee(이선영),Ji-Hyun Ahn(안지현),Jaetaek Kim(김재택),In-Kyung Kim(김인경),Ho-Shik Kim(김호식) 한국생명과학회 2008 생명과학회지 Vol.18 No.11

Prostaglandin A₂ (PGA₂)는 사람 골육종 세포인 U2OS 세포주에서 apoptosis와 heme oxygenase (HO)-1의 발현을 함께 유도하였다. PGA₂에 의한 apoptosis는 HO-1의 과도한 발현이나 HO-1에 대한 small interfering RNA에 의한 발현저하에 의하여 변동되지 않았으나 H₂O₂에 의한 세포사망은 HO-1의 발현 수준에 반비례하여 변동되었다. 또한 thiol antioxidant인 N-acetyl-L-cysteine (NAC)은 PGA₂에 의한 세포사망과 HO-1의 발현 증가를 모두 차단하였지만, non-thiol antioxidant인 butylated hydroxyanisole (BHA)과 ascorbic acid는 세포사망과 HO-1의 발현 유도를 차단하지 않았다. 이와 같은 결과들은 PGA₂는 산화성 손상에 의해서가 아니라 PGA₂의 thiol-reactivity에 의하여 apoptosis와 HO-1의 발현을 유도하며, HO-1의 발현은 PGA₂에 의한 apoptosis와는 독립적인 현상이거나 기능적으로 apoptosis 유도의 하부에 위치하고 apoptosis의 진행에는 기여하지 않을 것이라는 것을 시사해 준다. Prostaglandin A₂ (PGA₂), one of cyclopentenone PGs, induced both apoptosis and heme oxygenase (HO)-1 expression in U2OS cells. PGA₂-induced apoptosis was not perturbed by either over-expression or knock-down of HO-1, whereas H₂O₂-induced cell death was inversely modulated by the expression level of HO-1. In addition, N-acetyl-L-cysteine (NAC), a thiol antioxidant, blocked both apoptosis and HO-1 expression induced by PGA₂. But, non-thiol antioxidants like butylated hydorxyanisole (BHA) and ascorbic acid did not block either apoptosis or HO-1-induction. Taken together, these results suggest that PGA₂ induces both apoptosis and HO-1 expression, which are critically related to the thiol-reactivity of PGA₂, but not oxidative stress, and HO-1 expression may be independent or functionally located downstream of apoptosis by PGA₂ without contribution to apoptosis progression.

Stain improvement in the white button mushroom ‘Seolgang’ and its varietal characteristics in Agaricus bisporus

Byung-Joo Lee,Mi-Ae Lee,Yong-Gyun Kim,Kwang-Won Lee,Yong-Pyo Lim,Byung-Eui Lee,Ho-Yeon Song 한국버섯학회 2012 한국버섯학회지 Vol.10 No.4

The button mushroom (Agaricus bisporus) is one of the most widely cultivated important edible mushroom species. In the breeding of new button mushroom, ‘Seolgang’ was developed by crossing two monokaryons ‘CM020913-27’ and ‘SSU423-31’. Because of the secondarily homothallism, only a small percentage of the basidia produce 3 or 4 spores, which are mostly haploid (n) and do not fruit. Single spore cultures derived from these types of spores produce a vegetative mycelium that also contain a variable number of genetically identical nuclei per cell called monokaryon. The lack of clamp connections between monokaryon and dikaryon required a series of mycelial culture and fruiting test. After crossing, hybrids were cultivated on a small scale and on a commercial scale at a farm. For this, the spawn was made by a commercial spawn producer and the spawned compost by a commercial compost producer. Mycelial growth of ‘Seolgang’ on CDA was better at 20℃ and 25℃ when it was compared with that of ‘505 Ho’. The mature cap shape of new strain ‘Seolgang’ is oblate spheroid and the immature cap shape is round to oblate spheroid. The cap diameter was 41.2 mm on average. In comparison with white strain ‘505 Ho’, the strain had a yield that was 9% higher. It produced fruiting bodies which had a higher weight on average per fruiting body and were 19% firmer with a good shelf life. Days of fruiting body were 3-4 days later than those of ‘505 Ho’. The physical characteristics such as elasticity, chewiness, adhesiveness were better than that of ‘505 Ho’. Genetic analysis of the new strain ‘Seolgang’ showed different profiles compared to ‘505 Ho’, CM02913-27, SSU413-31, when RAPD primers A02 and O04 were used.

Nutlin-3 induces HO-1 expression by activating JNK in a transcription-independent manner of p53

CHOE, YUN-JEONG,LEE, SUN-YOUNG,KO, KYUNG WON,SHIN, SEOK JOON,KIM, HO-SHIK Spandidos Publications 2014 International journal of oncology Vol.44 No.3

A recent study reported that p53 can induce HO-1 by directly binding to the putative p53 responsive element in the HO-1 promoter. In this study, we report that nutlin-3, a small molecule antagonist of HDM2, induces the transcription of HO-1 in a transcription-independent manner of p53. Nutlin-3 induced HO-1 expression at the level of transcription in human cancer cells such as U2OS and RKO cells. This induction of HO-1 did not occur in SAOS cells in which p53 was mutated and was prevented by knocking down the p53 protein using p53 siRNA transfection, but not by PFT-alpha, an inhibitor of the transcriptional activity of p53. Accompanying HO-1 expression, nutlin-3 stimulated the accumulation of ROS and the phosphorylation of MAPKs such as JNK, p38 MAPK and ERK1/2. Nutlin-3-induced HO-1 expression was suppressed by TEMPO, a ROS scavenger, and chemical inhibitors of JNK and p38 MAPK but not ERK1/2. In addition, nutlin-3-induced phosphorylation of JNK but not p38 MAPK was inhibited by TEMPO. Notably, the levels of nutlin-3-induced ROS were correlated with the mitochondrial translocation of p53 and this induction was prevented by PFT-beta, an inhibitor of the mitochondrial translocation of p53. Consistent with the effect of the ROS scavenger and MAPK inhibitors, PFT-beta reduced HO-1 expression and the phosphorylation of JNK induced by nutlin-3. In the experiments of analyzing cell death, the knockdown of HO-1 augmented nutlin-3-induced apoptosis. Collectively, these results suggest that nutlin-3 induces HO-1 expression via the activation of both JNK which is dependent on ROS generated by p53 translocated to the mitochondria and p38 MAPK which appears to be stimulated by a ROS-independent mechanism, and this HO-1 induction may inhibit nutlin-3-induced apoptosis, constituting a negative feedback loop of p53-induced apoptosis.

Hypoxia-Responsive MicroRNA-101 Promotes Angiogenesis <i>via</i> Heme Oxygenase-1/Vascular Endothelial Growth Factor Axis by Targeting Cullin 3

Kim, Ji-Hee,Lee, Kwang-Soon,Lee, Dong-Keon,Kim, Joohwan,Kwak, Su-Nam,Ha, Kwon-Soo,Choe, Jongseon,Won, Moo-Ho,Cho, Byung-Ryul,Jeoung, Dooil,Lee, Hansoo,Kwon, Young-Guen,Kim, Young-Myeong Mary Ann Liebert 2014 Antioxidants & redox signaling Vol.21 No.18

<P>Aims: Hypoxia induces expression of various genes and microRNAs (miRs) that regulate angiogenesis and vascular function. In this study, we investigated a new functional role of new hypoxia-responsive miR-101 in angiogenesis and its underlying mechanism for regulating heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) expression. Results: We found that hypoxia induced miR-101, which binds to the 3 ' untranslated region of cullin 3 (Cul3) and stabilizes nuclear factor erythroid-derived 2-related factor 2 (Nrf2) via inhibition of the proteasomal degradation pathway. miR-101 overexpression promoted Nrf2 nuclear accumulation, which was accompanied with increases in HO-1 induction, VEGF expression, and endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) production. The elevated NO-induced S-nitrosylation of Kelch-like ECH-associated protein 1 and subsequent induction of Nrf2-dependent HO-1 lead to further elevation of VEGF production via a positive feedback loop between the Nrf2/HO-1 and VEGF/eNOS axes. Moreover, miR-101 promoted angiogenic signals and angiogenesis both in vitro and in vivo, and these events were attenuated by inhibiting the biological activity of HO-1, VEGF, or eNOS. Moreover, these effects were also observed in aortic rings from HO-1(+/-) and eNOS(-/-) mice. Local overexpression of miR-101 improved therapeutic angiogenesis and perfusion recovery in the ischemic mouse hindlimb, whereas antagomiR-101 diminished regional blood flow. Innovation: Hypoxia-responsive miR-101 stimulates angiogenesis by activating the HO-1/VEGF/eNOS axis via Cul3 targeting. Thus, miR-101 is a novel angiomir. Conclusion: Our results provide new mechanistic insights into a functional role of miR-101 as a potential therapeutic target in angiogenesis and vascular remodeling. Antioxid. Redox Signal. 21, 2469-2482.</P>

An Investigation on the Life of Master Won Guk Lee, the Creator of Chung-Do-Kwan

( Seon Young Jung ),( Jun Ho Lee ),( Seung Woo Shin ),( Chun Hwan Cho ),( Seung Hyun Jang ),( Won Shin ) 경남대학교 기초과학연구소 2014 기초과학지 Vol.31 No.-

The purpose of this study is to review (or, investigate) the life of Won Guk Lee. He is the creator of Chung-Do-Kwan, which is one of the five original Taekwondo kwans. Data was gathered from advanced research, newspapers, documentaries, the Internet, magazines, and journals etc. Thus, we were able to create a sequence of events based on the research data. First, we can say that in Won Guk Lee``s career, he created Chung-Do-Kwan and brought Dangsoodo to Korea. These events have had a significant development on Taekwondo. Second, Taekwondo curriculum, which was published by Won Guk Lee, established the foundation of Taekwondo poomsae, as well as giving us the pure spirit of Korean martial arts.

동종골수이식 후 혈당 및 혈중 지질농도의 변화양상 및 관련인자

이원영,강무일,오은숙,오기원,손현식,윤건호,차봉연,이광우,손호영,강성구,신완식,민우성,김춘주 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.24 No.6

연구배경:골수이식은 비교적 젊은 연령의 환자들을 대상으로 하며 면역억제제의 사용기간이 비교적 짧으므로, 주로 고령의 만성 질환 환자에서 시행되는 고형장기이식에서와는 달리 당대사 및 지단백 대사에 있어서 많은 차이점이 있을 것으로 추측된다. 저자들은 전향적 연구를 통하여 골수이식 후 시기별로 혈당 및 혈중지단백 변화 양상을 알아보고 이와 관련된 임상인자들을 규명하고자 하였다. 방법:1998년 10월부터 1999년 8월까지 가톨릭대학교 성모병원에서 동종골수이식을 시행한 환자들 중 43명을 대상으로 이식 전 및 이식 후 1, 2, 3, 4주와 3개월, 6개월에 공복 혈당, 혈중 총 콜레스테롤, 중성지방, 고밀도지단백을 측정하여 골수이식 후 시기별 변화를 관찰하고 여러 임상인자들에 따른 차이를 알아보았다. 결과:1. 공복혈당은 골수이식 수 첫4주 동안 상승하였고 이후 감소하였으나 이식 6개월 시점의 평균 공복혈당은 이식 전보다 유의하게 높게 관찰되었다. 혈중 총 콜레스테롤은 이식 후 1주에 최고치를 형성하였고 이후 기저수준으로 회복되었다가 이식 수 3,6개월에 다시 증가하여 기저치에 비해 유의하게 높았다. 혈중 중성지방은 이식 후 1개월까지 유의하게 증가하였고 이후 감소하여, 3,6개월에는 기저치와 유의한 차이가 관찰되지 않았다. 혈중 고밀도지단백은 이식 후 2,3주에 이식 전보다 유의하게 감소하였고 이후 이식 전 수준으로 회복되었다. 혈중 저밀도지단백은 총 콜레스테롤의 변화와 매우 유사하였다. 2. 골수이식 후 6개월 시점에서 공복 혈당이 126㎎/dL이상인 환자는 7명(16%)이었다. 이들 환자들과 공복혈당 126㎎/dL 미만의 환자 36명을 비교한 결과, 공복혈당이 126㎎/dL 이상인 환자군에서 스테로이드 평균 투여량이 많았고 고밀도지단백이 유의하게 낮았다. 3. 이식편대숙주질환이 발생한 환자는 그렇지 않은 환자보다 이식 후 1, 2, 3주 및 6개월의 총 콜레스테롤이 더 낮았고, 3개월의 공복혈당이 더 높았다. 혈연골수이식 환자군은 비혈연골수이식 환자에 비해 투여된 스테로이드 용량이 더 적음에도 불구하고 이식 후 1, 2, 3주 및 6개월의 총 콜레스테롤 수치가 더 높았다. 스테로이드 고용량 투여군(하루 평균 7.5㎎기준)은 저용량군보다 이식 후 3개월 시점의 공복혈당이 더 높았으나 나머지 시점의 혈당, 혈중 지질농도에 있어서는 유의한 차이가 관찰되지 않았다. 결론:골수이식 후 초기시기에 주로 당 대사 및 지질대사이상이 관찰되며 이는 면역억제제 투여와 관련이 있음을 알 수 있었다. 면역억제제가 고용량 투여되는 합병증 발생 시 이들 대사이상에 관심을 기울여 대처해야 할 것이다. Background: In bone marrow transplantation(BMT), recipients are usually younger and immunosuppressants are open used in shorter period than in solid organ transplantation. Therefore, there might be a difference in glucose and lipid metabolism between BMT and solid organ transplantation. However, the serial changes of metabolic parameters following BMT have not been studied. Therefore, the aim of this study is to investigate the serial changes of blood glucose, lipids and the putative factors that are related with these changes after BMT. Methods: We have prospectively investigated 43 patients who underwent allogeneic BMT. Fasting plasma glucose(FPG), total cholesterol, triglyceride and high-density lipoprotein(HDL) were measured before BMT, and at 1, 2, 3, 4, 12 weeks and 6 months after BMT. The serial changes of these metabolic parameters according to clinical factors including type of BMT, mean daily steroid dosage, and occurrence of graft versus host disease (GVHD) were examined. Results: 1. Mean FPG level increased during 4 weeks after BMT and remained above basal value at post-transplant 6 months. Total Cholesterol level was increased during initial 4 weeks after BMT and was above basal value at post-BMT of 3 and 6 months. Triglyceride level was progressively increased during initial 4 weeks after BMT, but returned to basal value there after. HDL-cholesterol level was significantly decreased during initial 4 weeks after BMT, but returned to basal value there after. 2. Patients with FPG above 126 mg/dL and the other patients, the former received larger amounts of daily steroid and had lower HDL-cholesterol level. 3. The changes of metabolic parameters were different according to type of BMT, steroid dose, and occurrence of GVHD. Conclusion: Although there was increase of FPG, TC, TG and decrease of HDL-C during initial 4 weeks after BMT, these metabolic changes recovered slowly thereafter. Immunosuppressants are thought to be associated with these changes. Further observation will be needed for the long-term effect of BMT on metabolic changes(J Kor Diabetes Asso 24:689~698, 2000).

평가시스템이 연봉제 도입 효과에 미치는 영향에 대한 연구

이상호,이원우,김호원 한국생산성학회 2004 生産性論集 Vol.18 No.2

This study examines the effect of performance appraisal systems in companies with merit pay systems. Particularly, the two aspects of performance appraisal systems are examined in relation to the degree of improvement in perceived overall productivity, organizational commitment, satisfaction with pay, satisfaction with job, and motivation for skill development compared with them before the introduction of merit pay systems. Those two aspects of performance appraisal systems include whether the companies use management by objective (MBO) methods for performance appraisals, and whether the companies provide formal rater training. In addition, the effect of employee participation in MBO is examined in case of the companies with a merit pay systems as well as MBO methods. A total of 74 companies responded to the questionnaires. According to correlation and regression analyses using the total sample, MBO and rater training are shown to be related to the degree of improvement in outcome variables. It is also shown that employee participation in MBO relates to the degree of improvement in outcome variables according to analyses using 48 samples with MBO. The importance of appropriate performance appraisal system is further discussed in the companies with merit pay systems.

馬山彎 周邊 沿岸 海水의 Vibrio의 分布에 關한 硏究

이호원,남호창,이민웅 경남대학교 환경문제연구소 1989 환경연구 Vol.11 No.-

A study on the distributions of environmental factors and Vibrio was carried out through sea water from 70 sites at the 7 coastal areas in Masan bay from March to April, 1989. The sea water temperatures were ranged 10.8-14.6°C and the mean was 13.0°C, It was highest at Sokchon, 13.7-14.6°C. The values of pH were 7.47-8.02 and the mean was 7.82. It was highest at WonJon, pH 7.84-8.02. The values of salinity were 24.6-30.6‰ and the mean was 27.5‰. It was highest at Yong-Won, 28.1- 30.6‰. Vibrio strains were isolated from all the 7 areas, at 23 sites (32.9%) among 70 sites. They were identified V. pgrahaemolyticus, V. alginolyticus and V. metschnikovii. V. parahaemolyticus was isolated at 8 sites ; V. alginolyticus, at 20 sites : V. metschnikovill. at 3 sites among 70 sites. And 65 Vibrio (23.2%) strains were isolated from examined NaCl concentrations of total 280 APW(Alkaline Pepton Waters). Among 65 strains 14 strains (21.5%) were V. parahaemolyticus from 1%, 4% and 7%;47 strains (72.3%) were V. alginolyticus from 1%, 4%, 7% and 10%;4 stains (6.2%)j were V. metschnikovii from 1% and 4% NaCl APW. And among 65 strains, 21 strains(30.3%) were isolated from 1%;22 strains (31.4%), from 4%, 16 strains (22.9%), from 7%;and 6 strains (8,6%), from 10% NaCl APW.

KAERI 부지 주변의 환경선량 측정을 위한 온라인 감마선량 감시시스템

이정호,박두원,이원윤,이현덕,최용호,김삼랑,홍광희,이창우 대한방사선 방어학회 1994 방사선방어학회지 Vol.19 No.2

환경감마선량 변동을 감시하기 위해 한국원자력연구소 부지 주변에 온라인 감마선량 감시망을 구성하였다. 모니터링 포스트에 설치된 전리함 검출기에 의해 측정된 자료는 무선전송방식으로 중앙통제소에 전송되어 실시간으로 감시된다. 무선전송 방식은 자료의 전송, 처리 및 자자에 신뢰도가 높고 경제적이었다. 감시시스템은 급격한 선량증가시 조기경보체제와 연결할 수 있게 하였다. On-line gamma monitoring system around KSERI-site was set up to monitor the radiation fluctuations in environment. Data on gamma exposure rates measured by the ionication chamber in the monitoring posts are transmitted to a computer of central control station with radio telemetry transmission and reliable on handing and storing of data. This monitroing system can triger an early warning system in the event of abnormal radiation levels.

Involvement of Nrf2-Mediated Upregulation of Heme Oxygenase-1 in Mollugin-Induced Growth Inhibition and Apoptosis in Human Oral Cancer Cells

Lee, Young-Man,Auh, Q-Schick,Lee, Deok-Won,Kim, Jun-Yeol,Jung, Ha-Jin,Lee, Seung-Ho,Kim, Eun-Cheol Hindawi Publishing Corporation 2013 BioMed research international Vol.2013 No.-

<P>Although previous studies have shown that mollugin, a bioactive phytochemical isolated from <I>Rubia cordifolia</I> L. (Rubiaceae), exhibits antitumor effects, its biological activity in oral cancer has not been reported. We thus investigated the effects and putative mechanism of apoptosis induced by mollugin in human oral squamous cell carcinoma cells (OSCCs). Results show that mollugin induces cell death in a dose-dependent manner in primary and metastatic OSCCs. Mollugin-induced cell death involved apoptosis, characterized by the appearance of nuclear shrinkage, flow cytometric analysis of sub-G<SUB>1</SUB> phase arrest, and annexin V-FITC and propidium iodide staining. Western blot analysis and RT-PCR revealed that mollugin suppressed activation of NF-<I><I>κ</I></I>B and NF-<I><I>κ</I></I>B-dependent gene products involved in antiapoptosis (Bcl-2 and Bcl-xl), invasion (MMP-9 and ICAM-1), and angiogenesis (FGF-2 and VEGF). Furthermore, mollugin induced the activation of p38, ERK, and JNK and the expression of heme oxygenase-1 (HO-1) and nuclear factor E2–related factor 2 (Nrf2). Mollugin-induced growth inhibition and apoptosis of HO-1 were reversed by an HO-1 inhibitor and Nrf2 siRNA. Collectively, this is the first report to demonstrate the effectiveness of mollugin as a candidate for a chemotherapeutic agent in OSCCs via the upregulation of the HO-1 and Nrf2 pathways and the downregulation of NF-<I><I>κ</I></I>B.</P>