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.

Heme oxygenase-1 mediated protective effect of methyl gallate on cadmium-induced cytotoxicity in cultured mouse mesangial cells

Cha, Seok-Ho,Suh, Chang-Kook The Korean Society of Toxicogenomics and Toxicopro 2010 Molecular & cellular toxicology Vol.6 No.2

To clarify the effect of a phytochemical, methyl gallate (MG) on a heavy metal (cadmium)-induced renal toxicity, cytotoxicity and the change of heme oxygenase-1 (HO-1) gene expression was studied using cultured mouse renal glomerular mesangial cells (MMC). By employing RT-PCR and Western blotting analysis, we have examined the HO-1 induction in MMCs that were treated with $Cd^{2+}$ and/or MG. Using MTT assay we have also examined the cytoprotective effect of HO-1 induction against the cytotoxicity caused by toxic dose of $Cd^{2+}$. In MMCs exposed to $Cd^{2+}$ and MG, expression of HO-1 (mRNA and protein) was increased in a concentration- and time-dependent manner. The increments of HO-1 mRNA and protein expressions by $Cd^{2+}$ and MG were inhibited by the treatment of the cells with actinomycin D, an inhibitor of transcription. The decreased viability of the cells by $Cd^{2+}$ was partially recovered by the treatment of MG and this recovery by the MG was reduced by the treatment of zinc protoporphyrin IX (a HO-1 inhibitor). From these results, methyl gallate might have cytoprotective effect on $Cd^{2+}$-induced cytotoxicity that is related with heme oxygenase-1 induction.

Combined Gene Therapy with Hypoxia-Inducible Factor-1α and Heme Oxygenase-1 for Therapeutic Angiogenesis

Bhang, Suk Ho,Kim, Ju Hee,Yang, Hee Seok,La, Wan-Geun,Lee, Tae-Jin,Kim, Ga Hee,Kim, Hyun Ah,Lee, Minhyung,Kim, Byung-Soo Mary Ann Liebert 2011 Tissue engineering. Part A Vol.17 No.7

<P>Transfection with either hypoxia-inducible factor-1α (HIF-1α) or heme oxygenase-1 (HO-1) gene can induce neovascularization in ischemic tissues. Although expression of transfected HIF-1α gene occurs rapidly, the expressed HIF-1α protein degrades quickly, limiting its therapeutic efficacy. Meanwhile, expressed HO-1 protein does not rapidly undergo degradation, but gene expression occurs a couple of days after transfection, resulting in apoptosis and a delay in angiogenesis in ischemic tissues at the incipient period of HO-1 gene transfection. We hypothesize that combined delivery of HIF-1α and HO-1 gene will enhance antiapoptosis and neovascularization in ischemic tissue compared with HIF-1α or HO-1 single-gene therapy. To test this hypothesis, ischemic mouse hindlimbs were treated with HIF-1α and/or HO-1 gene therapy. The combined gene therapy proved superior to both single-gene therapies, resulting in rapid expression of HIF-1α gene and long-term maintenance of expressed HO-1 protein. The apoptosis in the ischemic region was significantly less, and angiogenic growth factor secretion and angiogenesis were greater in the combined gene therapy than in either of the single-gene therapies. Our results suggest that a combined gene therapy of HIF-1α and HO-1 enhances the transfection of both genes and improves angiogenesis compared with either single-gene therapy.</P>

사례보고 : 하수오 복용 후 발생한 재발성 독성 간염 1예

배상훈 ( Sang Hoon Bae ),김동현 ( Dong Hyun Kim ),배영석 ( Young Seok Bae ),이광재 ( Kwang Jae Lee ),김동완 ( Dong Wan Kim ),윤정빈 ( Jeoung Bin Yoon ),홍준호 ( Joon Ho Hong ),김상현 ( Sang Hyun Kim ) 대한간학회 2010 Clinical and Molecular Hepatology(대한간학회지) Vol.16 No.2

Toxic hepatitis has been reported as a major cause of acute hepatitis, but its potential induction by herbal remedies and/or health foods is usually neglected. We experienced a case of toxic hepatitis associated with Polygoni multiflori, a Chinese herb commonly known as Ho-Shou-Wu. A 54-year-old woman consumed Ho-Shou-Wu for 1 month, after which she experienced fatigue and overall weakness. A diagnosis of toxic hepatitis was made based on her clinical history, the findings for viral markers and other laboratory data, and ultrasonography. Her condition improved considerably after she stopped taking Ho-Shou-Wu. However, she resumed taking Ho-Shou-Wu immediately after discharge from hospital, which aggravated her symptoms and liver function. She was immediately readmitted and stopped taking Ho-Shou-Wu. Her relapse into hepatitis immediate after resuming consumption of the herb is strongly indicative of the validity of Koch`s postulate in this case.

Upregulation of heme oxygenase-1 by ginsenoside Ro attenuates lipopolysaccharide-induced inflammation in macrophage cells

Sokho Kim,Myung-Hoon Oh,Bum-Seok Kim,Won-Il Kim,Ho-Seong Cho,Byoung-Yong Park,Chul Park,Gee-Wook Shin,Jungkee Kwon 고려인삼학회 2015 Journal of Ginseng Research Vol.39 No.4

Background: The beneficial effects of ginsenoside species have been well demonstrated in a number of studies. However, the function of ginsenoside Ro (GRo), an oleanane-type saponin, has not been suffi- ciently investigated. Thus, the aim of the present study was to investigate the anti-inflammatory effects of GRo in vitro using the Raw 264.7 mouse macrophage cell line treated with lipopolysaccharide (LPS), and to clarify the possible mechanism of GRo involving heme oxygenase-1 (HO-1), which itself plays a critical role in self-defense in the presence of inflammatory stress. Methods: Raw 264.7 cells were pretreated with GRo (up to 200mM) for 1 h before treatment with 1 mg/ mL LPS, and both cell viability and inflammatory markers involving HO-1 were evaluated. Results: GRo significantly increased cell viability in a dose dependent manner following treatment with LPS, and decreased levels of reactive oxygen species and nitric oxide. GRo decreased inflammatory cytokines such as nitric oxide synthase and cyclooxygenase-2 induced by LPS. Moreover, GRo increased the expression of HO-1 in a dose dependent manner. Cotreatment of GRo with tin protoporphyrin IX, a selective inhibitor of HO-1, not only inhibited upregulation of HO-1 induced by GRo, but also reversed the anti-inflammatory effect of GRo in LPS treated Raw 264.7 cells. Conclusion: GRo induces anti-inflammatory effects following treatment with LPS via upregulation of HO-1.

Upregulation of heme oxygenase-1 by ginsenoside Ro attenuates lipopolysaccharide-induced inflammation in macrophage cells

Kim, Sokho,Oh, Myung-Hoon,Kim, Bum-Seok,Kim, Won-Il,Cho, Ho-Seong,Park, Byoung-Yong,Park, Chul,Shin, Gee-Wook,Kwon, Jungkee The Korean Society of Ginseng 2015 Journal of Ginseng Research Vol.39 No.4

Background: The beneficial effects of ginsenoside species have been well demonstrated in a number of studies. However, the function of ginsenoside Ro (GRo), an oleanane-type saponin, has not been sufficiently investigated. Thus, the aim of the present study was to investigate the anti-inflammatory effects of GRo in vitro using the Raw 264.7 mouse macrophage cell line treated with lipopolysaccharide (LPS), and to clarify the possible mechanism of GRo involving heme oxygenase-1 (HO-1), which itself plays a critical role in self-defense in the presence of inflammatory stress. Methods: Raw 264.7 cells were pretreated with GRo (up to $200{\mu}M$) for 1 h before treatment with 1 mg/mL LPS, and both cell viability and inflammatory markers involving HO-1 were evaluated. Results: GRo significantly increased cell viability in a dose dependent manner following treatment with LPS, and decreased levels of reactive oxygen species and nitric oxide. GRo decreased inflammatory cytokines such as nitric oxide synthase and cyclooxygenase-2 induced by LPS. Moreover, GRo increased the expression of HO-1 in a dose dependent manner. Cotreatment of GRo with tin protoporphyrin IX, a selective inhibitor of HO-1, not only inhibited upregulation of HO-1 induced by GRo, but also reversed the anti-inflammatory effect of GRo in LPS treated Raw 264.7 cells. Conclusion: GRo induces anti-inflammatory effects following treatment with LPS via upregulation of HO-1.

Superconducting MgB2 Wire Drawing Considering Anisotropic Hardening Behavior and Hydrostatic Effect

Young‑Seok Oh,Ho Won Lee,Kook‑Chae Chung,Duck‑Young Hwang,Seong‑Hoon Kang,Jeong Whan Yoon 대한금속·재료학회 2022 METALS AND MATERIALS International Vol.28 No.7

Numerical modeling was conducted to investigate the deformation behavior of powder mixture during multi-pass drawingprocesses for multi-filamentary MgB2wire. A modified Drucker-Prager Cap (DPC) model with an elliptical cap surface usingthe new material characterization method was developed to capture the anisotropic hardening behavior and hydrostatic effectof the powder mixture. A number of uniaxial die compaction, cold isostatic pressing, diametrical compression, and uniaxialcompression tests were conducted using different powder densities to characterize the modified DPC model. A commercialfinite element software ABAQUS with a user subroutine was used to simulate the drawing of the MgB2wire. The densityand area fraction of the powder mixture during the wire-drawing process were verified with experimental results. The differencein packing density at the inner and outer filaments of the MgB2wire was successfully captured by simulation. Inaddition, the effect of the initial packing density on the superconducting properties of MgB2wire was numerically studied. It is shown that the increase in the superconducting area, which results from a high initial packing density, should be moreeffective compared to the increase in the grain connectivity in enhancing the critical current properties for the MgB2wirewhen the final packing density is saturated after a number of drawing processes.

Anti-Inflammatory Effect of By-Products from<i>Haliotis discus hannai</i>in RAW 264.7 Cells

Rho, Ho-Seok,Kim, Hyang,Kim, Jung-Ae,Karadeniz, Fatih,Ahn, Byul-Nim,Nam, Ki-Ho,Seo, Youngwan,Kong, Chang-Suk Hindawi Limited 2015 Journal of chemistry Vol.2015 No.-

<P>Several reports promoted the potential of shellfish due to their ability to act as antioxidant, anti-inflammatory, and antimicrobial agents. Pacific abalone,<I>Haliotis discus hannai</I>viscera is, reported to possess bioactivities such as antioxidative stress and anti-inflammatory. In this study, anti-inflammatory potential of mucus-secreting glands from shell-shucking waste of<I>H. discus hannai</I>was evaluated using RAW 264.7 mouse macrophage cell model. Results indicated that presence of<I>H. discus hannai</I>mucosubstance by-products (AM) significantly lowered the nitric oxide (NO) production along the expressional suppression of inflammatory mediators such as cytokines TNF-<I>α</I>, IL-1<I>β</I>, and IL-6 and enzymes iNOS and COX-2. Also, AM was shown to increase expression of anti-inflammatory response mediator HO-1. Presence of AM also scavenged the free radicals<I>in vitro</I>. In conclusion, by-products of<I>H. discus hannai</I>are suggested to possess notable anti-inflammatory potential which promotes the possibility of utilization as functional food ingredient.</P>

전국 응급의학과 수련병원의 응급실 병력지에 대한 분석

임태호,임훈,이종호,강형구,장문준,조광현,장석준,김승호,정상원 대한응급의학회 2000 대한응급의학회지 Vol.11 No.4

Background: This study was designed to analyze the current emergency department(ED) medical records of teaching hospitals in Korea. Methods: The five-item questionnaires were mailed to the EDs of 40 hospitals. Among them, 27 questionnaires and 35 ED medical records were returned for reply rates of 67.5% and 87.5%, respectively. Results: 1) The actual number of data elements in the ED medical records used by each hospital varies widely. It ranges from 1 to 15 data elements with an average of 7.5 data elements. 2) Thirteen data elements, signature of nurse, checklist style in review of systems, checklist style in physical examination, neurologic examination, figure of face, Glasgow coma scale, trauma scale, treatment plan, mode of transfer, condition on transfer, documents sent with patient, condition on discharge or discharge instruction, use of pediatric chart and vaccination history are used by less than 50% of the medical records examined. 3) There was no difference in the total number of data elements or in redesign and computerization of ED medical record based on the location of the hospital, the type of hospital administration, or the number of years since the start of EM residency program. 4) There was a statistically increased number of data elements in redesigned medical records. 5) In the survey, 89% of the residents replied that medical records needed to be redesigned. With respect to uniformity, 58% of the residents disagreed. A well-designed checklist chart rather than a descriptive chart was preferred by 89% of the residents. Conclusion: The currently used ED medical records have much room for improvement. The age of the ED had little impact on the quality of ED medical records. More attention and effort in this field are needed. In addition, The Korean Society of Emergency Medicine should provide guidelines for ED medical records.

황해도 탈춤음악의 전승과 선율구조

김호석 ( Ho Seok Kim ) 한국음악사학회 2009 한국음악사학보 Vol.43 No.-

한국의 탈춤은 춤·대사·음악의 3요소로 구성되는데, 그중에서도 음악은 춤의 반주로 사용되는 반주음악과 대사 중에 나오는 노래로 구분할 수 있다. 탈춤의 춤과 대사는 일찍이 관심있는 학자들의 연구와 채록활동을 통해 그동안 많은 연구논문과 저서들이 발표되었지만, 음악에 관하여는 최근에 임혜정과 이진원이 발표한 논문 외에 필자가 출간한 『탈춤음악본총서 1·2·3』권이 고작이다. 따라서 본고는 탈춤음악 중 필자가 직접 전승 및 연주활동에 참여하고 있는 황해도탈춤을 중심으로 반주음악의 전승실태와 선율구조의 특징 및 연주기법에 대하여 알아보고, 대사 중에 연희자들이 부르는 노래의 선율구조에 대하여 살펴보고자 한다. 먼저 반주음악의 전승실태에 관해서는, 6.25전쟁 후 월남한 예술인을 통해 명맥을 이어온 황해도피리가락이 오선보를 활용한 그룹지도를 통해 현재 봉산탈춤·강령탈춤·은율탈춤 등 황해도탈춤의 반주음악악사들에게 전승되어 연주되고 있을 뿐만 아니라, 2000년부터는 한국예술종합학교 전통예술원을 비롯한 서울지역 주요대학 국악과의 피리전공자들을 대상으로 열린 하계강습을 통해 서도풍류라는 연주곡목으로 전승되어 연주회장에서 수회 발표되기도 하였다. 이러한 황해도탈춤의 반주음악은 피리2·대금1·해금1·장고1·북1·징1 등 모두 6명으로 구성된 삼현육각편성으로 연주되고 있지만, 편의상 쌍피리와 타악기의 편성으로 연주하기도 하며, 놀이의 흥을 돋우기 위해 길놀이 및 몇몇 과장에서는 태평소와 타악기만으로 연주하기도 한다. 현재 연주되고 있는 황해도탈춤의 반주음악에는 해주가락·재령가락·은율가락 등이 있는데, 해주가락과 재령가락은 봉산탈춤과 강령탈춤의 전 과장에서 반주음악으로 연주되고 있으며, 특히 해주가락 중 타령은 은율탈춤공연에서도 연주되고 있다. 반면 은율가락인 긴염불은 은율탈춤공연에서만 제한적으로 연주되고 있는 실정이다. 또한 연주기법에 있어서 해주가락의 경우 서도소리의 창법이 묻어있지만, 재령가락과 은율가락의 경우에는 연주기법은 해주가락의 특징을 적용하되 선율구조는 「솔-라-도-레-미」로 되어있다. 다음으로 황해도탈춤에서 연희자들이 부르는 노래의 선율구조를 살펴보면, 강령탈춤에 나오는 물레타령이 유일하게 수심가토리이고 경토리가 가장 많으며, 육자백이토리와 메나리토리의 곡이 골고루 분포되어 있다. 또한 경토리로 되어있는 곡의 일부는 창법에 있어서 서도소리의 창법을 적용하기도 한다. Hwanghaedo Mask Dance Music could be preserved till today because of devotional endeavors of Pak Tong-sin, Kim Yong-t`aek, and Yang So-un. Hwanghaedo mask dance music is divided into the instrumental accompaniment music and songs that are sung by performers. The accompaniment music is divided into Pak Tong-sin`s Hwanghaedo p`iri Tunes that are performed in Pongsan t`alch`um, Kangryong t`alch`um, and Unyul t`alch`um, and Kim Yong-t`aek`s Unyul Tunes and t`aep`yongso Tunes that are played in Unyul t`alch`um. Songs were transmitted from Yang So-un to all of three organizations preserving Hwanghaedo mask dance and 68 songs survive. Hwanghaedo p`iri Tunes consists of Haeju tunes - yombul, t`aryong, and kukkori - that were transmitted to from Chong Mok-tong and Yi Ho-yun and Chaeryong tune - t`aryon sinawi - that Pak adopted from Chaeryong p`iri players. These pieces are played throughout the entire acts in Pongsan t`alch`um and Kangryong t`alch`um and t`aryong is played in Unyul t`alch`um. Among Kim Yong-t`aek`s Unyul Tunes and t`aep`yongso Tunes, kin yombul, chajin tomburi, tol changdan, and unyul kut changdan are played as accompaniment music of Unyul t`alch`um. Hwanghaedo p`iri Tunes, that were transmitted to the writer from Pak Tong-sin, are still in the process of transmission to the next generation throughout courses in the Korean National University of Arts and special summer courses in every other year. Besides, it became an independent instrumental genre to be performed on the stage being recognized as sodo p`ungnyu. The accompaniment music of Hwanghaedo mask dance are divided into three categories according to it musical frames. The first is Haeju karak that consist of sol-(la)-re -mi; yombul, t`aryong, and kukkori are haeju karak. Second, the scale is formed with sol-la-do-re-mi including t`aryong karak, t`aryong sinawi, unyul karak, kin yombul, and t`aep`yongso karak, chajin tomburi, tol changdan, and unyul kut changdan. Third, the scale is formed with la-do-re-mi-sol. The instrumentation of the accompaniment music of Hwanghaedo mask dance should be samhyon yukkak; however, only Pongsan t`alch`um is accompanied with Samhyon yukkak; Kangroong t`alch`um only with two piri and one taegum; Unyul t`alch`um with two p`iri and one t`aepyongso. Performing techniques of p`iri, witch is the main instrument of the accompaniment music, can be discussed with the three main techniques. The first technique is the throat technique which is expressing a little lower tone than re as a staccato on the first hole. The second technique is expressing re by holding the reed deeply vibrating the pitch deeply on the second hole. The third technique is expressing the pitch of the back hole with the long sustentation and vibration at the end. These techniques not only appear in Hwanghae-do piri Tunes but also Unyul Tunes. Songs that are sung in Hwanghaedo mask dances are divided according to dances and categorized according to their tori, regional styles. If the scale of a song is the same as sol-la-do-re-mi or la-do-re-mi-sol, it is kyong t`ori. If the scale of a song is the same as mi-la-ti-do-re with the characteristic ti, it is yukchabaegi t`ori. Mi-sol-la-do-re is known as menari t`ori, and re-la-do or la-mi-sol, which is perfect fifth above re-la-do, is susimga t`ori. Some of non-harmonic tones - for example, passing tones, neighboring tones, and escape tones - may appear. Among sixty-eight pieces that are sung in Hwanghaedo mask dance, thirty-five pieces are kyong t`ori. which is more than a half, twenty one pieces are yukchabaegi t`ori, which is 1/3 of the entire, ten pieces are in menari t`ori, one is susimga t`ori, and one is p`yong sijo. As utilizing the staff notation instead of the oral transmission, the system of transmission became more efficient and it made the group lecture possible; and thus, Hwanghaedo p`iri Tunes, which were in danger to be lost, have been popularized in the traditional music society. In addition, it became rigid not only as the accompaniment music of Hwanghaedo mask dance but also as an instrumental genre known as sodo p`ungnyu.