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.

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.

Protective Effect of Heme Oxygenase-1 on High Glucose-Induced Pancreatic β-Cell Injury

Lee, Eun-Mi,Lee, Young-Eun,Lee, Esder,Ryu, Gyeong Ryul,Ko, Seung-Hyun,Moon, Sung-Dae,Song, Ki-Ho,Ahn, Yu-Bae Korean Diabetes Association 2011 Diabetes and Metabolism Journal Vol.35 No.5

<P><B>Background</B></P><P>Glucose toxicity that is caused by chronic exposure to a high glucose concentration leads to islet dysfunction and induces apoptosis in pancreatic β-cells. Heme oxygenase-1 (HO-1) has been identified as an anti-apoptotic and cytoprotective gene. The purpose of this study is to investigate whether HO-1 up-regulation when using metalloprotophyrin (cobalt protoporphyrin, CoPP) could protect pancreatic β-cells from high glucose-induced apoptosis.</P><P><B>Methods</B></P><P>Reverse transcription-polymerase chain reaction was performed to analyze the CoPP-induced mRNA expression of HO-1. Cell viability of INS-1 cells cultured in the presence of CoPP was examined by acridine orange/propidium iodide staining. The generation of intracellular reactive oxygen species (ROS) was measured using flow cytometry. Glucose stimulated insulin secretion (GSIS) was determined following incubation with CoPP in different glucose concentrations.</P><P><B>Results</B></P><P>CoPP increased HO-1 mRNA expression in both a dose- and time-dependent manner. Overexpression of HO-1 inhibited caspase-3, and the number of dead cells in the presence of CoPP was significantly decreased when exposed to high glucose conditions (HG). CoPP also decreased the generation of intracellular ROS by 50% during 72 hours of culture with HG. However, decreased GSIS was not recovered even in the presence of CoPP.</P><P><B>Conclusion</B></P><P>Our data suggest that CoPP-induced HO-1 up-regulation results in protection from high glucose-induced apoptosis in INS-1 cells; however, glucose stimulated insulin secretion is not restored.</P>

Identification of AFLP Marker Linked to a SCN Resistant Gene in Soybean

Ko,Mi-Suk,Kim,Myung-Sik,Han,Soung-Jin,Chung,Jong-Il,Kang,Jin-Ho 한국자원식물학회 2002 Plant Resources Vol.5 No.3

The soybean cyst nematode (Heterodera glycines Inchinoe; SCN) is a devastating pest of soybean and is responsible for significant losses in yield. The use of resistant cultivars is the effective method to reduce or eliminate SCN damage. The objective of this research is to identify AFLP markers linked to the SCN resistant genes. Bulked genomic DNA was made from resistant and susceptible genotypes to SCN and a total of 19 primer combinations were used. About 31 fragments were detected per primer combination. The banding patterns were readily distinguished in resistant and susceptible bulked genotypes. Polymorphic fragments were detected between resistant and susceptible bulked genotypes in the primer combination of CGT/GGC, CAG/GTG and CTC/GAG. In primer combinations of CGT/GGC and CAG/GTG, bulked resistant genotype produced a polymorphic bands. However, in primer of CTC/GAG, bulked susceptible genotype produced a polymorphic fragments. Three AFLP markers identified as a polymorphic fragments between bulked genomic DNA were mapped in 85 F2 population. Among them, only two markers, CGT/GGC and CTC/GAG, was linked and was mapped. Broad application of AFLP marker would be possible for improving resistant cultivars to SCN.

Anti-Inflammatory and Cytoprotective Effects of TMC-256C1 from Marine-Derived Fungus <i>Aspergillus</i> sp. SF-6354 via up-Regulation of Heme Oxygenase-1 in Murine Hippocampal and Microglial Cell Lines

Kim, Dong-Cheol,Cho, Kwang-Ho,Ko, Wonmin,Yoon, Chi-Su,Sohn, Jae Hak,Yim, Joung Han,Kim, Youn-Chul,Oh, Hyuncheol MDPI AG 2016 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.17 No.4

<P>In the course of searching for bioactive secondary metabolites from marine fungi, TMC-256C1 was isolated from an ethyl acetate extract of the marine-derived fungus <I>Aspergillus</I> sp. SF6354. TMC-256C1 displayed anti-neuroinflammatory effect in BV2 microglial cells induced by lipopolysaccharides (LPS) as well as neuroprotective effect against glutamate-stimulated neurotoxicity in mouse hippocampal HT22 cells. TMC-256C1 was shown to develop a cellular resistance to oxidative damage caused by glutamate-induced cytotoxicity and reactive oxygen species (ROS) generation in HT22 cells, and suppress the inflammation process in LPS-stimulated BV2 cells. Furthermore, the neuroprotective and anti-neuroinflammatory activities of TMC-256C1 were associated with upregulated expression of heme oxygenase (HO)-1 and nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) in HT22 and BV2 cells. We also found that TMC-256C1 activated p38 mitogen-activated protein kinases (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways in HT22 and BV2 cells. These results demonstrated that TMC-256C1 activates HO-1 protein expression, probably by increasing nuclear Nrf2 levels via the activation of the p38 MAPK and PI3K/Akt pathways.</P>

Azithromycin으로 치료한 임신 중 쓰쓰가무시병 1예

김광석,최진욱,서호종,김기훈,박성호,서광섭,고성만,김순혜,김호정 대한감염학회 2001 감염 Vol.33 No.5

We report a case of tsutsugamushi disease in a 26 year-old pregnant woman who was treated with azithromycin. Her gestation period was 27 weeks and she admitted with fever, rash, and eschar on the right shoulder. Currently recommended medications for the treatment of scrub typhus are doxycycline or chloramphenicol. But, these drugs are class D drugs according to the U.S. Food and Drug Administration (FDA) Fetal Risk Summary, so they couldn't be used to treat pregnant women. Recently, a few case reports suggested that azithromycin, a relatively new macrolide antibiotic, was effective and safe for the treatment of scrub typhus in pregnant women. And, there is no evidence that azithromycin causes harmful effects to the developing fetus or to children. On the basis of current in vivo test that confirms the effectiveness of azithromycin, it may be the drug of choice for the treatment of scrub typhus in pregnant women and children. (Korean J Infect Dis 33:380-382, 2001)

5 GHz WLAN용 SiGe HBT MMIC 차동형 전압제어발진기 설계

고호정,김창우 慶熙大學校 레이저 工學硏究所 2002 레이저공학 Vol.13 No.-

An SiGe HBT MMIC differential-type voltage controlled oscillator(VCO) has been designed for wirless LAN applications. The varactor has been used in this VCO, The VCO includes two varactors formed by shorted-connection of emitter and base terminals of HBT's. From the simulation, The VCO exhibits 310-MHz tunning range at 4.785 GHz and -3.8 ± 0.04 dBm output power with a control voltage range from 0.5 to 2.5 V. The phase noise of the VCO is -104 dBc/Hz at 1 MHz offset from the 4.785 GHz carrier. The total power consumption of the oscillator is 45㎽ at a supply voltage of 3.0 V.

Broiler의 성장에 Atonik가 미치는 影響

高永杜,宋又準,河正基,姜鎬祚 慶尙大學校 1972 論文集 Vol.11 No.-

Broiler에 Atonik의 添加效果를 究明하기 위하여 Pilch line Broiler 初生雛 100首를 가지고 Atonil 添加水準 0, 0.3, 0.5, 0.7%를 Completely randomized design에 의해 實驗한 結果를 要約하면 다음과 같다. 1. 增體量에 있어 0.7%를 添加하므로서 약간 改善되었으나 統計的인 有意性이 없었다. 2. 飼料效率은 添加量이 많을수록 떨어지는 경향이 였고 日當增體量은 역시 0.3% 區가 가장 좋았으나 統計的 有意性이 없었다. 3. 血液性狀에 있어 赤血球와 血淸蛋白總量은 對照區에 비해 添加量이 많을수록 增加하였고 白血球와 Hemoglobin 含量은 對照區가 제일 적었다. 4. 斃死率은 各區間에 별차가 없었고 이들은 管理 부주의 및 쥐의 피해였다. This experiment was conducted to investigate the effect of Atonik supplementation on the growth rate, feed efficiency and blood picture of broiler. For this study, 100 starting chickens of pilch line were fed for 6 weeks. Atonik, the plant growth regulator, was supplemented in the levels of 0, 0.3, 0.5 and 0.7% in the water of chicks. The results obtained are summarized as follows; 1. It was found that 0.7% supplementation of atonik slightly improved growth rate but no statistical difference was detected. 2. Feel efficiency was decreased in the treatment given more supplement although no statistical difference was detected. 3. The number of red blood cell and hemoglobin content were increased in the treatment used more supplement hut the number of white blood cell and total serum protein content were decreased in the treatment used more supplement. 4. Mortality was not found tile difference between the treatments.

武者小路實篤의 「友情」에 관한 小考

高浩錫 진주여자전문대학 1993 論文集 Vol.16 No.-

「友情」は野島, 大宮, 杉予の三人が愛と友情という人間的現像を通して, 自然の意志の存在と攝理, さらにその下で生きる人間のトラマを描いた作品である. ニ人の靑年と一人の女性は愛と友情との純情な次元で苦鬪しているのである. ここには 人間の可能性への無限の析りがあって,强靭な生命力としての具現者としての自覺をもち,それを最大限にのばすことである. 三人の間には最後まで人生の眞摯な態度があり, 互いへの信賴と尊敬の心は失っていないのである. 「人間には精神があります. 魂があります.충けらからは耶蘇も釋迦も出ません」と主張したように野島と六宮の人生觀と生き方の下には强い求道性と理想主義が息づぃている. 迷いを知らない代りに,彼らは明を信じて今の苦しみに耐えることを知る人??である.

團體交涉의 對象事項에 관한 法規制

高豪晟 제주대학교 1991 논문집 Vol.32 No.1

Since the Government prohibited the collective bargaining on some so-called management issues, the problem of statutory regulations on the subjects of collective bargaining has been debated fiercely in Korea. This problem has to be solved from the perspect of below. First, the statutory regulations on the subjects of collective bargaining in Korea basically rely on the distinction of the mandatory subjects, permissive subjects and illegal subjects. This distinction is drawn with reference to the judge-made law on this problem in the United States. Second, the practical conclusions on this distinction in Korea are very different from those in the United States. In the United States, only about the madatory subjects is the refusal to bargain treated as illegal and the strike, as legal. In Korea, it is the same as in United States that only about the mandatory subjects the refusal to bargain should be treated as illegal, but it is different from in the United states that about the permissive subjects the strike should be treated as legal in principle. Third, in Korea the permissive subjects are so general and inclusive to be defined as the subjects other than the illegal subjects. From this perspective is crucial the problem of what the illegal subjects are. But the illegal subjects of collective bargaing in Korea shoud be regarded to be rare in practice with respect to the peacefull character of collective bargains. Of course, there are some management issues that seems to be illegal subjects of strike. But there are no management issues that are illegal subjects of collective bargaing. Fourth, the mandatory subjects of collective bargaining in Korea about which the refusal to bargain should be treated as illegal and the strike, as legal, fall into two groups:those which deal with the relationship between the employer and the employees and those which deal with the relationship between the employer and the union.