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>

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.

디지털 팔름 메이킹에 있어서 노출의 문제

고호빈 호남대학교산업기술연구소 2008 산업기술연구논문집 Vol.14 No.-

All objects reflect the light received from light sources. A camera is the machine of recording the light that is ret1ected by the objects. The brightness and darkness in the film image depend on the amount of light. And the color in the film image is determined according to the wavelengths of light. Exposure is what a camera regulates the amount of light. Accordingly, exposure is the most central problem in film making. Even in digital film making, the importance of exposure cannot be reduced and the optical principles in exposure cannot be varied. If any problems about exposure arise in digital film making , they only originate with being strange in the functions of digital film making equipment, and therefore may be easily solved to master the operating techniques of digital film making in light of the optical principles in exposure, and mastering the operating techniques. Regardless of difference in media and methods, the core in the problems about exposure rather relies on achieving exposure that can take advantage of a cameraman’ s aesthetic and creative intention beyond technological and arithmetic exposure. 모든 사물들은 광원으로부터 빛을 받아 고유의 반사율에 따라 반사한다. 차메라는 사물이 반사하는 빛을 받아들여 기록하는 기계이다. 빛의 량에 따라 영상의 밝고 어두움이 결정되고, 어떤 파장의 빛이냐에 따라 색이 결정된다. 촬영 시에 카메라가 받아들일 빛의 량을 조절하는 것이 노출이다. 따라서 노출은 영상 제작에 있어 가장 핵심적인 문제이다. 디지럴 방식의 영상 제작에 있어서도 노출의 중요성이 감소될 수 없고, 노출의 광학적 원리가 변할 수는 없다. 디지럴 필름 메이킹에서 일어날 수 있는 노출의 문제란 단지 디지털 영상 제작 장비들의 기능들에 익숙하지 않다는 데에서 오는 것일 뿐이다. 이는 노출의 광학적 원리에 비추어 디지털 영상 제작 장비들의 운용 기술을 습득한다면 능히 해결할 수 있는 문제다. 매체나 방식의 차이를 막론하고 노출 문제의 핵심은 오히려 테크놀로지적이고 산술적인 노출을 넘어 촬영자의 미학적 의도를 살릴 수 있는 노출을 성취하는 데 있다.

안양시 생활만족도에 관한 통계적 분석

고왕경,김호일 안양대학교 자연과학연구소 1995 自然科學硏究 Vol.2 No.-

설문조사에 의하여 안양시민의 각 동별 생활 편의 측면에서의 만족도, 주거환경에 대한 만족도, 경제생활 영위에 대한 만족도등 3가지 만족도 측면에서 분석하였다. 분석에 사용된 도구는 집락분석과 Dual scaling방법이다. 집락분석에 의하여 31개동을 각 만족도별로 그룹화하였고 Dual scaling방법에 의하여 각 구별로 동들에 대한 종류별 만족도를 조사하였다. We analyze each Dong about the degree of 3-type satisfaction for Anyang citizen by sample survey. These are the living facility, the dwelling environment and the economic likelihood. The statistical tools used are the clustering analysis and the dual scaling. A Dong is grouping in accordance to its degree by the clustering analysis, and we analyze each Dong with ones by the dual scaling method.

자궁 경부에서 발생한 상피내 암종과 침윤성 암종의 간질 변화에 관한 병리조직학적 연구

고성민,노광을,이민전,김용임,이미자,전호종,서재홍 조선대학교 1993 The Medical Journal of Chosun University Vol.18 No.2

Connective tissue seems to be involved in malignancy by lytic processes as a crucial element in invasive growth. This looks relatively simple, but data have emerged that the stroma is not just a passive but rather an active participant. Recent advances in the borderland between cancer and connective tissue research have increasingly made it clear that the relationship between malignant tissue and its stroma is a very intricate one. The present study was performed in order to investigate the variety of stromal reactivity and alterations of basement membrane accompanying malignant growth and the distribution of Langerhans cells and T and B lymphocytes in cervical epithelium affected by intaepithelial neoplasia and invasive cervical carcinoma. The subjects in this were 14 cervicitis, 42 cervical intraepithelial neoplasia, 14 microinvasive cervical carcinoma and 14 invasive cervical carcinomas. A total of 84 formalin-fixed and paraffin-embedded specimens of normal, inflamed and neoplastic uterine cervix have been studied in order to correlate the epithelial changes with the expression of α-smooth muscle actin, S-100 protein, α_1-antichymotrypsin, lysozyme, LCA, CD20, UCHL1, OPD4, CD1, CD4, CD8, CD68 and typeⅣ collagen in stroma. The results of immunohistochemical and electron microscopical examinations yield virtually identical findings 1) The number of α-smooth muscle actin positive cells and the intensity of stain were related to the increasing grading of cervical intraepithelial neoplasia and invasive cervical carcinoma. 2) Normal cervix and cervical intraepithelial neoplasia grade Ⅰ and Ⅱ showed continuous basement membrane but invasive cervical carcinoma showed highly variable basement membrane deposition ranging from continuous to almost completely absent. 3) The cervical intraepithelial neoplasia Ⅲ and invasive cervical carcinoma showed an increase in spindle shaped Langerhans cells associated with increased numbers of stroma and intraepithelial lymphoid cells. The evaluation of collagen Ⅳ in basement membrane, S-100 protein and CD1 in Langerhans cells and α-smooth muscle actin in stromal cells of the uterine cervix may be an useful adjunct to diagnostic criteria of cervical intraepithrlial neoplasia and invasive cervical carcinoma, and may help understanding of the mechanisms of mesenchymal epithelial interactions during neoplasia.