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.

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)

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>

日本語 動詞活用에 관한 硏究

高浩錫 진주여자전문대학 1992 論文集 Vol.15 No.-

In spit of many problems of school gramar in conjugating verbs of Japanese language, it is still widely used as a teaching method. If school grammar is unreasonable, the more appropriate grammatical system should be suggested. So this thesis is intended to analyse the problems of school grammar in verb conjugations and to suggest new conjugation paradigm which, I think is more suitable for learning modern spoken Japanese. The six conjugations of verbs now used in school grammar has some problems to be applied to modern spoken Japanese ; for it is inconsistent in its terms and different conjugations are treated as the same one. Therefore new thirteen conjugations of verbs are suggested in this thesis ; Dictionary form, Continuative form, TE(て)form, TA(た)form, Subjunctive form, TARI(たり)form, Tentative form, Imperative form, Conditional form, Neqative form, Passive-Honorable form, Causative form, Potential form.

芥川龍之介の「羅生門」小考

고호석 진주여자전문대학 2000 論文集 Vol.23 No.-

Among various writing background of Rasyomon, there can be counted on fingers Akutagawa's heart-break as one of the most important reason. Such loneliness of heart-break made him write a delightful novel aparted from the reality as possible. Because of foster parents and uncle's egoism, Akutagawa who gave up to marry Yoshida described persistent and clear egoism through the servant's psychological state out of the actor in Rasyomon. In other words, the main theme of Rasyomon is based on the egoism, such as, the trend of servant s mental state and inevitably criminal act to survive in life. This egoism is a sort of severe experience against failure love of Akutagawa himself, and so, this novel was written under the unavoidable reality, abominable actualism between foster parents and writer himself.

탈중심적 영화에 대한 연구

고호빈 호남대학교 2007 학술논문집 Vol.28 No.2

This paper contemplates the issues of decentering in the modern cinema. The mainstream cinema for the film history is the narrative cinema. This cinema maneuvers the apparatus and codes to unify the points of view and time. Although it is minor, a series of the contemporary movies that can be named the 'acentric' films expose such a discontinuity and incoherence. The point of view and time in the acentric films is ceaselessly increased and acentred. There are several points of views and theories to interpret it. However, it is the general consensus that most of codes, system of representations, and discourses are exposed as the ideological nature. However, the assertion of the later structuralism philosopher, Gilles Deleuze, is unique and attentive. We, human beings as the living body, cannot sustain such an excessive stimulation of the images. Therefore, Deleuze argues, in order to avoid the excessive dissipation arising from the image, the circuitry of our brain is operated. The circuitry of brain that Deleuze referred to is the rationality or understanding. Following the argument of Deleuze, our function of rationality critically civilizes the image for the survival of our existence. In other words, it forms the order, coordinates and codifies. All visual codes including the perspectives, artistic codes, social and cultural regulations and systems may be understood in such a context.

영화제작에 있어서 디지털 인터미디어트

고호빈 호남대학교산업기술연구소 2007 산업기술연구논문집 Vol.13 No.-

이미지 테크놀러지와 소프트웨어나 하드웨어 형태의 디지털 이미지 제작 도구들을 영화 제작에 활용하는 것을 '디지털 인터미디어트'라고 한다. 원래 영화란 필름이 발명되었기 때문에 가능해진 매체이다. 지난 세기 동안 영화를 제작하는 데 있어 필름을 사용하지 않은 경우는 없었다. 필름은 영화의 동의어로 쓰일 정 도였다. 한편,지난 세기 후반 TV와 비디오라는 전자영상매체가 등장했다. 필름 영화와 전자영상매체는 한편으로는 경쟁하면서,또 다른 한편으로는 상호 보완적으로 발전했다. 여기에서 상호 보완적이었다는 것은 필름 영화가 TV와 비디오의 콘텐츠로 전환되어 보급됨으로써 전자영상매체의 발전에 큰 기여를 했다는 뜻이다. 그러나 TV와 비디오 콘텐츠가 필름 영화로 전환되는 경우는 드물었다. 가장 큰 이유는 TV와 비디오가 구현하는 영상과 음향의 질과 미학적 표현력이 필름 영화에 비해 열등했기 때문이다. 21세기,TV와 비디오의 원천 기술이 디지털 방식으로 바뀌고,HD 포맷이 개발되면서 상황이 달라지고 있다. 디지털 HD 포뱃의 영상과 음향의 질은 필름의 그것과 대등한 수준으로 평가된다. 그리고 디지털 방식의 영상 제작 공정은 대단히 경제적이고 효율적이다. 이제 영화 제작에 디지털 제작 공정을 채택하지 않을 이유가 없다. 미래의 영화는 필 름 없는 영화,디지털 영화가 될 것이다. Using digital image technology or digital image making tools in the form of software or hardware on film making is called the 'digital intermediate.' Originally, the cinema became a medium through the invention of film. During the past century it was impossible to produce the cinema using film. It even became so that the word 'film' was used as a synonym for 'cinema'. In the mean while, during the last few decades, the electronic media such as TV and video were introduced. The film media and the electronic media have been competing with each other, on the other hand, developing complementarily. What is meant here by 'complementarily' is that the distribution of the films as the contents or programs on TV and video contributed greatly to the development of the electronic media. However, not often were the contents of TV and video converted into the films. This is because the quality of image, sound, and artistic expression in TV and video were inferior to those of the films In the 21st century, as the older analog technology for TV and video changed to the digital and the HD format was developed, a new situation has been formed. The quality of image and sound of the digital HD format can now be equal to those of the film. Also, film making by the digital method is very economic and efficient. There is now no reason not to choose the digital process when making films. The cinema of the future will become a digital cinema of 'the film without film".