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.

Comparison of trophic factors changes in the hippocampal CA1 region between the young and adult gerbil induced by transient cerebral ischemia.

Yan, Bing Chun,Park, Joon Ha,Kim, Sung Koo,Choi, Jung Hoon,Lee, Choong Hyun,Yoo, Ki-Yeon,Kwon, Young-Geun,Kim, Young-Myeong,Kim, Jong-Dai,Won, Moo-Ho Kluwer Academic/Plenum Publishers 2012 Cellular and molecular neurobiology Vol.32 No.8

<P>In the present study, we investigated neuronal death/damage in the gerbil hippocampal CA1 region (CA1) and compared changes in some trophic factors, such as brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF), in the CA1 between the adult and young gerbils after 5 min of transient cerebral ischemia. Most of pyramidal neurons (89%) were damaged 4 days after ischemia-reperfusion (I-R) in the adult; however, in the young, about 59% of pyramidal neurons were damaged 7 days after I-R. The immunoreactivity and levels of BDNF and VEGF, not GDNF, in the CA1 of the normal young were lower than those in the normal adult. Four days after I-R in the adult group, the immunoreactivity and levels of BDNF and VEGF were distinctively decreased, and the immunoreactivity and level of GDNF were increased. However, in the young group, all of their immunoreactivities and levels were much higher than those in the normal young group. From 7 days after I-R, all the immunoreactivities and levels were apparently decreased compared to those of the normal adult and young. In brief, we confirmed our recent finding: more delayed and less neuronal death occurred in the young following I-R, and we newly found that the immunoreactivities of trophic factors, such as BDNF, GDNF, and VEGF, in the stratum pyramidale of the CA1 in the young gerbil were much higher than those in the adult gerbil 4 days after transient cerebral ischemia.</P>

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.

Heme oxygenase-1 (HO-1)/carbon monoxide (CO) axis suppresses RANKL-induced osteoclastic differentiation by inhibiting redox-sensitive NF-κB activation

( Sun-uk Bak ),( Suji Kim ),( Hae-jun Hwang ),( Jung-a Yun ),( Wan-sung Kim ),( Moo-ho Won ),( Ji-yoon Kim ),( Kwon-soo Ha ),( Young-guen Kwon ),( Young-myeong Kim ) 생화학분자생물학회(구 한국생화학분자생물학회) 2017 BMB Reports Vol.50 No.2

Heme oxygenase (HO-1) catalyzes heme to carbon monoxide (CO), biliverdin/bilirubin, and iron and is known to prevent the pathogenesis of several human diseases. We assessed the beneficial effect of heme degradation products on osteoclastogenesis induced by receptor activator of NF-κB ligand (RANKL). Treatment of RAW264.7 cells with CORM-2 (a CO donor) and bilirubin, but not with iron, decreased RANKLinduced osteoclastogenesis, with CORM-2 having a more potent anti-osteogenic effect. CORM-2 also inhibited RANKLinduced osteoclastogenesis and osteoclastic resorption activity in marrow-derived macrophages. Treatment with hemin, a HO-1 inducer, strongly inhibited RANKL-induced osteoclastogenesis in wild-type macrophages, but was ineffective in HO-1^+/-cells. CORM-2 reduced RANKL-induced NFATc1 expression by inhibiting IKK-dependent NF-κB activation and reactive oxygen species production. These results suggest that CO potently inhibits RANKL-induced osteoclastogenesis by inhibiting redox-sensitive NF-κB-mediated NFATc1 expression. Our findings indicate that HO-1/CO can act as an antiresorption agent and reduce bone loss by blocking osteoclast differentiation. [BMB Reports 2017; 50(2): 103-108]

忠南 錦山郡 西臺山 一帶의 나비目 昆蟲相

남상호,조영호,장석원,박영준,이선영,나선희 대전대학교 기초과학연구소 2002 自然科學 Vol.13 No.2

충청남도 금산군 서대산 일대의 나비목 곤충상을 조사한 결과 22과 344종 1,936개체가 조사되었다. 이중 밤나방과가 102종 589개체, 자나방과가 67종 440개체로 이 2과가 전체의 50%이상을 차지하였다. 자나방과의 두줄가지나방은 1,936 개체중 85개체가 채집되어 4.4%의 가장 높은 우점도를 나타냈다. 월별 우점종은 4월 노랑무늬물결자나방, 5월 별박이세줄나비, 6월 목도리불나방, 7월 청백무늬밤나방, 8월 두줄가지나방, 9월은 털뿔가지나방이 조사되었다. 월별 종다양도는 4월 2.95, 5월 3.37, 6월 4.63, 7월 4.62, 8월 4.23, 9월은 2.97이었으며, 평균 종다양도는 3.80으로 서대산 일대의 나비목 곤충상은 비교적 양호한 편으로 조사되었다. This study was carried out to investigate Lepidopterous insect fauna from Mt. Seodae in Geumsan-gun, Chungnam. The samples were collected from April to September in 2001. Total 1,936 individuals belonging to 344 species, 22 families of Lepidoptera were collected. The sum of individuals belonging to Noctuidae and Geometridae exceed 50% of the collected samples in that Noctuidae was consisted of 102 species 589 individuals and Geometridae was 67 species 440 individuals. The dominant species in surveyed area was Rikiosatoa grisea of Geometridae, the dominant species by month were Idiotephria amelia in April, Neptis pryeri in May, Paraona staudinger in June, Ercheia niveostrigata in July, Rikiosatoa grisea in August and Alcis angulifera in September respectively. Species diversity indices by month were 2.93 in April, 3.37 in May, 4.63 in June, 4.62 in July, 4.23 in August and 2.97 in September respectively. Mean species diversity index was 3.80.

Involvement of Nrf2-Mediated Upregulation of Heme Oxygenase-1 in Mollugin-Induced Growth Inhibition and Apoptosis in Human Oral Cancer Cells

Lee, Young-Man,Auh, Q-Schick,Lee, Deok-Won,Kim, Jun-Yeol,Jung, Ha-Jin,Lee, Seung-Ho,Kim, Eun-Cheol Hindawi Publishing Corporation 2013 BioMed research international Vol.2013 No.-

<P>Although previous studies have shown that mollugin, a bioactive phytochemical isolated from <I>Rubia cordifolia</I> L. (Rubiaceae), exhibits antitumor effects, its biological activity in oral cancer has not been reported. We thus investigated the effects and putative mechanism of apoptosis induced by mollugin in human oral squamous cell carcinoma cells (OSCCs). Results show that mollugin induces cell death in a dose-dependent manner in primary and metastatic OSCCs. Mollugin-induced cell death involved apoptosis, characterized by the appearance of nuclear shrinkage, flow cytometric analysis of sub-G<SUB>1</SUB> phase arrest, and annexin V-FITC and propidium iodide staining. Western blot analysis and RT-PCR revealed that mollugin suppressed activation of NF-<I><I>κ</I></I>B and NF-<I><I>κ</I></I>B-dependent gene products involved in antiapoptosis (Bcl-2 and Bcl-xl), invasion (MMP-9 and ICAM-1), and angiogenesis (FGF-2 and VEGF). Furthermore, mollugin induced the activation of p38, ERK, and JNK and the expression of heme oxygenase-1 (HO-1) and nuclear factor E2–related factor 2 (Nrf2). Mollugin-induced growth inhibition and apoptosis of HO-1 were reversed by an HO-1 inhibitor and Nrf2 siRNA. Collectively, this is the first report to demonstrate the effectiveness of mollugin as a candidate for a chemotherapeutic agent in OSCCs via the upregulation of the HO-1 and Nrf2 pathways and the downregulation of NF-<I><I>κ</I></I>B.</P>

골수이식 후 골밀도 및 골대사의 변화 : 2년 추적관찰 2-Year Prospective Study

이원영,강무일,오은숙,오기원,한제호,손현식,윤건호,차봉연,이광우,손호영,강성구,신완식,민우성,김춘추 대한내분비학회 2000 Endocrinology and metabolism Vol.15 No.4·5

만성 승모판폐쇄부전증 이환견의 치료 1례

김영실,박정희,신영지,박성준,이영원,최호정,송근호 忠南大學校 獸醫科大學 動物醫科學硏究所 2005 動物醫科學硏究誌 Vol.13 No.-

A 8 years old intact male Shih-tzu dog with respiratory distress was referred to the Veterinary Medical Teaching Hospital of Chungnam National University. The dog also had a history of several episodes of syncope prior to visit. Physical examination revealed tachypnea, panting, mucous membrane of pale and cyanosis. Holosystolic murmur at the left apex region by auscultation, left sided cardiac enlargement by thoracic radiography and mitral regurgitated flow by echocardiography were detected. Clinical signs were improved by treatment of diuretics, ACE inhibitor, bronchodilator and oxygen therapy.

동일한 환자에서 조혈모세포이식 전후의 호중구감소 기간 중 감염양상에 대한 비교연구 : 중심정맥관 관련 패혈증을 중심으로 Based on Central Venous Catheter Related Septicemia

류재호,노규태,이영석,이영호,권혁찬,김재석,김효진,이영민,박혜원,박근희 대한조혈모세포이식학회 2002 대한조혈모세포이식학회지 Vol.7 No.1

연구배경: 동일한 환자를 대상으로 조혈모세포이식 전 일반 병실에서의 관해유도 항암제치료 및 강화요법으로 인한 호중구감소 기간의 감염양상과 고용량 항암제치료 후 무균실에서의 조혈모세포이식 시 호중구감소 기간의 감염양상을 중심정맥관 관련 패혈증을 중심으로 비교 연구함으로써 효율적인 감염관리지침을 마련하고자 하였다. 대상 및 방법: 1999년 1월부터 2001년 7월까지 2년 7개월간 동아대학교병원 일반병실에서 악성혈액질환으로 항암제 치료를 받다가 조혈모세포이식을 시행받았던 22명을 대상으로 중심정맥관 관련 패혈증의 형태를 비교분석하였다. 결과: 대상 환자들의 일반병실과 무균실에서의 입원기간은 각각 32±13일, 33±19일, 호중구 감소기간은 15±12일, 17±18일, 호중구 감소기간의 발열 횟수는 14회, 14회로서 입원병실의 종류에 따른 차이는 없었다. 환자들의 중심정맥관 사용일수는 일반병실에서 29일(7~545일), 무균실에서 100.5일(25~606일)이었으며, 총 사용일수는 각각 1,515일, 3,250일로서 무균실에서의 중심정맥관 사용일수가 의미 있게 길었다(P=0.001). 중심정맥관 사용 일수에 대한 감염률은 각각 5.28/1,000일, 3.08/1,000일로서 일반병실에서 그 빈도가 높았으나 통계적 유의성은 보이지 않았다(P=0.141). 결론: 중심정맥관 삽입 후 일반병실에서 항암제 치료를 받던 환자가 조혈모세포이식을 위하여 무균실에 입원하는 경우, 중심정맥관을 교체하는 것이 감염관리를 위하여 바람직할 것으로 생각된다. Background: We compared the incidence of central venous catheter (CVC) related septicemia during neutropenic period in the same patient, which developed following chemotherapy for remission induction and consolidation, or hematopoietic stem cell transplantation (HSCT). Methods: We retrospectively reviewed the medical records and laboratory data of 22 patients with hematologic malignancies who received anticancer chemotherapy followed by HSCT at Dong-A University Hospital between January, 1999 and July, 2001. We investigated the duration of hospitalization, duration of neutropenic period, duration of catheterization, microbiologically documented organisms and incidence of CVC related septicemia. Results: The data in general ward (before HSCT) and laminar air flow room (after HSCT) were as follows: duration of hospitalization was 32±13 days and 33±19 days, duration of neutropenic period was 15±12 days and 17±18 days, median duration of catheterization was 29 days (7~545 days) and 100.5 days (25~606 days) (P=0.001), and incidence of CVC related septicemia was 5.28/1000 days and 3.08/1000 days, respectively. In the CVC related septicemia, the most common etiologic organism was coagulase negative staphylococcus. Conclusion: We suggest that the exchange of CVC before admission to laminar air flow room could decrease the incidence of CVC related septicemia in HSCT recipients.