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.

Mg₂SiO₄ : La, Ho 열형광선량계에서 활성제 농도가 글로우 커브에 미치는 영향 La, Ho TLD on Activation Concentration

김영국,손인호,채건식,노경석,오재근,이은숙 경남대학교 신소재연구소 1996 論文集 Vol.6 No.-

본 연구에서는 Mg₂SiO₄에 활성화 물질로 La, Ho를 첨가하여 열형광체를 제작하였고 불순물의 농도를 1wt.% ∼5 wt.%까지 변화시키면서 열평광강도의 glow curve를 측정하였다. 도한 열형광체의 glow curve를 peak shape법으로 분석해서 TL특성에 대한 포획 매개변수와 활성화 에너지, 발광차수, 선량의존성등을 조사하였으며, 그 물리적 특성을 조사하고 선량계로서 타당성과 실용성을 확인하였다. The Mg₂SiO₄: La, Ho thermoluminescent phospher has been prepared by sintring Mg₂SiO₄after doping the transition elements La and Ho. The heating rate is 10℃/sec at this thermoluminescent phospher are heated. The maximum peaks are found in the measured Mg₂SiO₄: La and Ho. TL glow curve at 229℃ and 345 C when the 1 wt.%-5 wt.%. The glow curve of TLD increased TL intensity and temperature of peak appears to the high temperature when the heating rate is l0℃/sec-25℃/sec. The activation energy of the main peak has been estimated by the peak shape method. The estimated activation energies are 1.77 eV. 1.52 eV respectively. The thermoluminescence process in Mg₂SiO₄: La and Ho are found to the 2nd order when the main peak of the glow curve is analyzed by peak shape method. The dose responses of Mg₂SiO₄: La and Ho TLD are linear up to intensity of X-ray.

N-acetyl cysteine inhibits H2O2-mediated reduction in the mineralization of MC3T3-E1 cells by down-regulating Nrf2/HO-1 pathway

( Daewoo Lee ),( Sung Ho Kook ),( Hyeok Ji ),( Seung Ah Lee ),( Ki Choon Choi ),( Kyung Yeol Lee ),( Jeong Chae Lee ) 생화학분자생물학회(구 한국생화학분자생물학회) 2015 BMB Reports Vol.48 No.11

There are controversial findings regarding the roles of nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway on bone metabolism under oxidative stress. We investigated how Nrf2/HO-1 pathway affects osteoblast differentiation of MC3T3-E1 cells in response to hydrogen peroxide (H2O2), N-acetyl cysteine (NAC), or both. Exposing the cells to H2O2 decreased the alkaline phosphatase activity, calcium accumulation, and expression of osteoblast markers, such as osteocalcin and runt-related transcription factor-2. In contrast, H2O2 treatment increased the expression of Nrf2 and HO-1 in the cells. Treatment with hemin, a chemical HO-1 inducer, mimicked the inhibitory effect of H2O2 on osteoblast differentiation by increasing the HO-1 expression and decreasing the osteogenic marker genes. Pretreatment with NAC restored all changes induced by H2O2 to near normal levels in the cells. Collectively, our findings suggest that H2O2-mediated activation of Nrf2/HO-1 pathway negatively regulates the osteoblast differentiation, which is inhibited by NAC. [BMB Reports 2015; 48(11): 636-641]

Ethanol Extract of Ganoderma lucidum Augments Cellular Anti-oxidant Defense through Activation of Nrf2/HO-1

Lee, Yoo-hwan,Kim, Jung-hee,Song, Choon-ho,Jang, Kyung-jeon,kim, Cheol-hong,Kang, Ji-Sook,Choi, Yung-hyun,Yoon, Hyun-Min KOREAN PHARMACOPUNCTURE INSTITUTE 2016 Journal of pharmacopuncture Vol.19 No.1

Objectives: The mushroom Ganoderma lucidum has been widely used as a traditional herbal medicine for many years. Although several studies have focused on the anti-oxidative activity of this mushroom, the molecular mechanisms underlying its activity have not yet been clearly established. The present study investigated the cytoprotective effect of ethanol extract of Ganoderma lucidum (EGL) against oxidative stress (hydrogen peroxide, $H_2O_2$) and elucidated the underlying mechanisms in a C2C12 myoblast cell line. Methods: Oxidative stress markers were determined by using the comet assay to measure reactive oxygen species (ROS) generation and deoxyribonucleic acid (DNA) damage. Cell viability and Western blotting analyses were employed to evaluate the cellular response to EGL and $H_2O_2$ in C2C12 cells. Transfection with nuclear factor erythroid 2-related factor 2 (Nrf2)-specific small interfering ribonucleic acid (siRNA) was conducted to understand the relationship between Nrf2 expression and $H_2O_2$-induced growth inhibition. Results: The results showed that EGL effectively inhibited $H_2O_2$-induced growth and the generation of ROS. EGL markedly suppressed $H_2O_2$-induced comet-like DNA formation and phosphorylation of histone H2AX at serine 139 ($p-{\gamma}H2AX$), a widely used marker of DNA damage, suggesting that EGL prevented $H_2O_2$-induced DNA damage. Furthermore, the EGL treatment effectively induced the expression of Nrf2, as well as heme oxygenase-1 (HO-1), with parallel phosphorylation and nuclear translocation of Nrf2 in the C2C12 myoblasts. However, zinc protoporphyrin IX, a HO-1 inhibitor, significantly abolished the protective effects of EGL against $H_2O_2$-induced accumulation of ROS and reduced cell growth. Notably, transient transfection with Nrf2-specific siRNA attenuated the cytoprotective effects and HO-1 induction by EGL, indicating that EGL induced the expression of HO-1 in an Nrf2-dependent manner. Conclusion: Collectively, these results demonstrate that EGL augments the cellular anti-oxidant defense capacity through activation of Nrf2/HO-1, thereby protecting C2C12 myoblasts from $H_2O_2$-induced oxidative cytotoxicity.

Carbon monoxide prevents TNF-α-induced eNOS downregulation by inhibiting NF-κB-responsive miR-155-5p biogenesis

Choi, Seunghwan,Kim, Joohwan,Kim, Ji-Hee,Lee, Dong-Keon,Park, Wonjin,Park, Minsik,Kim, Suji,Hwang, Jong Yun,Won, Moo-Ho,Choi, Yoon Kyung,Ryoo, Sungwoo,Ha, Kwon-Soo,Kwon, Young-Guen,Kim, Young-Myeong Nature Publishing Group 2017 Experimental and molecular medicine Vol.49 No.11

<P>Heme oxygenase-1-derived carbon monoxide prevents inflammatory vascular disorders. To date, there is no clear evidence that HO-1/CO prevents endothelial dysfunction associated with the downregulation of endothelial NO synthesis in human endothelial cells stimulated with TNF-α. Here, we found that the CO-releasing compound CORM-2 prevented TNF-α-mediated decreases in eNOS expression and NO/cGMP production, without affecting eNOS promoter activity, by maintaining the functional activity of the <I>eNOS</I> mRNA 3′-untranslated region. By contrast, CORM-2 inhibited MIR155HG expression and miR-155-5p biogenesis in TNF-α-stimulated endothelial cells, resulting in recovery of the 3′-UTR activity of <I>eNOS</I> mRNA, a target of miR-155-5p. The beneficial effect of CORM-2 was blocked by an NF-κB inhibitor, a miR-155-5p mimic, a HO-1 inhibitor and siRNA against HO-1, indicating that CO rescues TNF-α-induced eNOS downregulation through NF-κB-responsive miR-155-5p expression via HO-1 induction; similar protective effects of ectopic HO-1 expression and bilirubin were observed in endothelial cells treated with TNF-α. Moreover, heme degradation products, except iron and <I>N</I>-acetylcysteine prevented H<SUB>2</SUB>O<SUB>2</SUB>-mediated miR-155-5p biogenesis and eNOS downregulation. These data demonstrate that CO prevents TNF-α-mediated eNOS downregulation by inhibiting redox-sensitive miR-155-5p biogenesis through a positive forward circuit between CO and HO-1 induction. This circuit may play an important preventive role in inflammatory endothelial dysfunction associated with human vascular diseases.</P>

항암제 AG60이 흰생쥐 위점막 상피세포의 DNA합성에 미치는 영향 : 자기방사법적연구

박경호,안의태,고정식,하상선,한영복,정영신,홍은경,유보림,김상건,이경영,강종구 대한해부학회 1999 Anatomy & Cell Biology Vol.32 No.1

Fatigue Crack Growth Behavior in Ultrafine Grained Low Carbon Steel

Ho,Kyung Kim,Myung-Il Choi,Chin-Sung Chung Dong-Hyuk Shin 대한기계학회 2002 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.16 No.10

Ultrafine grained (UFG) low carbon (0.15 wt.% C) steel produced by equal channel angular pressing (ECAP) was tested for investigating the effect of load ratio on the fatigue crack growth rate. Fatigue crack growth resistance and threshold of UFG steel were lower than that of as-received coarse grained steel. It was attributed to the less tortuous crack path. The UFG steel exhibited slightly higher crack growth rates and a lower △K_th with an increase of R ratio. The R ratio effect on crack growth rates and △K_th was basically indistinguishable at lower load ratio (R>0.3), compared to other alloys, which indicates that contribution of the crack closure vanishes. The crack growth rate curve for UFG steel exhibited a longer linear extension to the lower growth rate regime than that for the coarse grained as-received steel.<br/>

중추성 요붕증이 동반된 랑게르한스 세포 조직구증 1예

김진호,문준성,문선중,이지은,최재원,은미정,천경아,조인호,윤지성,원규장,이경희 신덕섭,이형우 영남대학교 의과대학 2005 Yeungnam University Journal of Medicine Vol.22 No.2

Central diabetes insipidus (DI) is a syndrome characterized by thirst, polydipsia and polyuria. Langerhans cell histiocytosis is one of the etiologies of DI. Recently we experienced a central DI associated with Langerhans cell histiocytosis. The 44 years old female patient complained right hip pain polydipsia and polyuria. We carried out water deprivation test. After vasopressin injection, urine osmotic pressure was increased form 109mOsmol/Kg to 327mOsmol/Kg (300%). Brain MRI showed a thickened pituitary stalk and at hot bone CT.CT guided biopsy revealed abnormal histiocytes proliferation and abundant lymphocytes, The final diagnosis was central DI associated with systemic Langerhans cell histiocytosis invading hip bone, L-spine and pituitary stalk. Desmopressin and etoposide chemotherapy were performed to the patient.

가집 『협률대성』의 편찬 특성과 전승ㆍ 향유의 문화적 의미

강경호(Kang, Kyung-Ho) 한국시조학회 2014 시조학논총 Vol.40 No.-

이 글은 조선후기 가곡문화의 흐름 속에서 가집 『協律大成』이 갖는 독자적 특징과 문화·향유 기반을 탐색하고 그 의미를 살펴보는 데에 그 목적이 있다. 『협률』은 국문학·국악학 분야에서 널리 알려진 가집임에도 불구하고 지금까지 학계에서는 가곡원류계 이본 가집정도로만 인식되고 있는 바 이 가집이 담고 있는 문학사적 또는 문화사적 의미와 가치를 밝히고자 하였다. 이 글의 논의는 크게 두 가지 방향에서 이루어졌다. 하나는 『협률』 이본 가집들의 성격과 그 전승 및 유통 양상에 대한 검토였고, 다른 하나는 『협률』의 내적체계 탐색을 통한 이 가집의 편찬 특성과 그 문화적 의미에 관한 연구였다. 우선 이본 검토에서는, 1) 『협률』의 이본 가집으로는 경농본과 가람본이 있는데, 가람본은 여러 표기 및 작품 표기에서 몇 가지 문제가 있다는 것이 밝혀졌다. 따라서 『협률』 연구는 경농본을 주 대상으로 삼고 살펴봐야 하며, 가람본은 그 비교 자료로 삼을 수 있다. 2) 이본들의 전승 양상에서는, 경농본은 소장자 이근우의 서울에서의 행적이나 활동시기 등을 볼 때 20세기 초에 입수된 것으로 추정되며, 편찬 시기도 이 시기와 멀지 않은 것으로 보인다. 또한 그 당시에도 가람본 등 다른 이본들이 계속 파생된 것으로 보아 『협률』이 20세기 초에 새로운 가곡원류계 가집으로 전승되었음을 알 수 있었다. 다음으로 『협률』의 편찬 특성 및 문화적 의미를 살펴본 결과, 1) 시조 작품이 수록된 ‘永言全部’에서는 전 작품의 연음표 표기, 안민영 작품의 탈락 현상, 〈태평가〉의 수록 위치의 변화 등이 확인되었다. 『협률』은 여러 가곡원류계 가집들에서 보이는 공통체계를 토대로 큰 변화 없이 만들어진 전형적인 가곡원류계 가집체계를 보이는데, 『협률』 편찬자는 중대엽을 포함한 전 곡에 연음표를 붙이면서 작품의 음악적 해석을 보다 충실히 시도하려 했으며, 편찬 당시 가곡문화의 음악환경에 맞춰 〈태평가〉의 위치를 조정하는 등 변화된 양상을 반영하려 하였다. 2) 가집 서두부에 수록된 ‘양금 가곡보’는 ‘弄’ 악곡의 분화, ‘始弄返樂’이라는 새로운 악곡의 수록, 小歌曲 중심의 수록 등 20세 초 가곡문화를 반영하고 있었다. 특히 이 양금 가곡보는 편찬자가 자신의 편찬 의식에 맞게 당대 가곡 작품들을 선별하여 가곡 연창 방식의 標本을 제시한 것이라 할 수 있다. 『협률』 ‘영언전부’에 대부분의 작품이 연음표까지 기입되어 수록되었음에도 불구하고, 편찬자가 양금 반주와 장구 장단까지 추가하여 가곡보를 제시한 것은 보다 세밀하고 실제적인 가곡 연행의 방식을 보여주기 위한 노력인 것이다. Purpose of this study is investigating character of Hyeopryuldaesung belonged to a Collection of Gagokwonryu series and fundamental base to possess and meaning in flow of sijo culture in the latter part of the Joseon Dynasty. Never theless Hyeopryuldaesung is well known in korean literary field, it just has been perceived as different type in a Collection of Gagokwonryu series until now. Also literary or cultural meaning and value has not been truly recognised. Hyeopryuldaesung is valuable gajip in gagok cultural history because of indicating compiling feature in early 20th century and transitional shape in this period. This study was progressed to two directions. One was study about character of these different version of gajips passing down & aspects of distribution, other one was reserch about this gajip’s character verified by research on compiling system and culural meaning. Result of first research is as follow as. 1) result on checking the bibliography of different version, different version of Hyeopryuldaesung is kyungnong versi on and garam version in present, after checking many problems about mark of poetries are discovered. Therefore, research about Hyeopryuldaesung should be base on kyungnong version, garam version can be database for preparing. 2) These differnet versions are presumed to be acquired in early 20th century by researching past activities and active periods of owner Lee Geun-woo. Also this gajip can be known to pass down continuously as new Collection of Gagokwonryu series in early 20th century by researching fact that many variety versions, for example garam version, were derived. Next, second study is result on investigating character of gajip’s compiling and cultural meaning. 1) Many things like mark of Yeoneum-Pyo[voice directing note symbols] mark in all sijo, eliminating phenomenon in An-minyoung’s poetries, changing location of Taepyungga’s potries are found in Yeongunjunboo included all sijo. Hyeopryuldaesung shows Gagokwonryu series’s traditional structure like other several Collections of Gagokwonryu series, but tried to adapt new aspects in that musical environment. 2) Gagokbo of Yang-geum attached on prologue of gajip adopt Gagok culture in early 20th century such as separation of Nong tune, Sinogbanrak(attachment of new tune), singing method focused on small gagok, etc. This Gagokbo of Yang-geum is good presented sample for sining method of gagok to be matched for compiler’s own intention by sorting gagok poetries in that age.