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]

Sulforaphane protects against acetaminophen-induced hepatotoxicity

Noh, Jung-Ran,Kim, Yong-Hoon,Hwang, Jung Hwan,Choi, Dong-Hee,Kim, Kyoung-Shim,Oh, Won-Keun,Lee, Chul-Ho Elsevier 2015 Food and chemical toxicology Vol.80 No.-

<P><B>Abstract</B></P> <P>Oxidative stress is closely associated with acetaminophen (APAP)-induced toxicity. Heme oxygenase-1 (HO-1), an antioxidant defense enzyme, has been shown to protect against oxidant-induced tissue injury. This study investigated whether sulforaphane (SFN), as a HO-1 inducer, plays a protective role against APAP hepatotoxicity <I>in vitro</I> and <I>in vivo</I>. Pretreatment of primary hepatocyte with SFN induced nuclear factor E2-factor related factor (Nrf2) target gene expression, especially HO-1 mRNA and protein expression, and suppressed APAP-induced glutathione (GSH) depletion and lipid peroxidation, which eventually leads to hepatocyte cell death. A comparable effect was observed in mice treated with APAP. Mice were treated with 300 mg/kg APAP 30 min after SFN (5 mg/kg) administration and were then sacrificed after 6 h. APAP alone caused severe liver injuries as characterized by increased plasma AST and ALT levels, GSH depletion, apoptosis, and 4-hydroxynonenal (4-HNE) formations. This APAP-induced liver damage was significantly attenuated by pretreatment with SFN. Furthermore, while hepatic reactive oxygen species (ROS) levels were increased by APAP exposure, pretreatment with SFN completely blocked ROS formation. These results suggest that SFN plays a protective role against APAP-mediated hepatotoxicity through antioxidant effects mediated by HO-1 induction. SFN has preventive action in oxidative stress-mediated liver injury.</P> <P><B>Highlights</B></P> <P> <UL> <LI> SFN pretreatment increases the cell viability against APAP-induced toxicity. </LI> <LI> SFN pretreatment protects depletion of cellular GSH after APAP treatment. </LI> <LI> SFN pretreatment enhances Nrf2 target gene expression, especially HO-1 after APAP treatment. </LI> <LI> SFN has protective effect against APAP overdose-induced liver injury <I>in vivo</I> model as well. </LI> </UL> </P>

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>

카드뮴에 의해 유발된 흰쥐 고환의 미세구조 및 단백질 변화

황일면,한승로,정옥,김수일,이영호,김원식 충남대학교 의과대학 지역사회의학연구소 2000 충남의대잡지 Vol.27 No.2

Although cadmium is a well known heavy metal which attacks testis and results male infertility, the mechanism of action in the testis is'nt still fully known. In the previous experiment, authors observed morphological changes in the testis, and found cadmium-induced death of all the spermatogenic cells and hemorrhagic necrosis within the seminiferous tubules, and apoptosis and death of interstitial cells and fibroblasts in the interstitial tissue of the testis. In this experiment, cadmium chloride (4 mg/kg of body weight) administered to the adult male rats(Sprague-Dawlcy) intraperitoneally and sacrificed 1 week after treatment. And electrophoresis, immunoprecipitation and Western blotting, and N-terminal analysis were performed to find the proteins changed after cadmium treatment in the testis. And the results were as follows; 1. Two proteins of molecular weight 42kDa and 21kDa disappeared after cadmium treatment. 2. The protein of 2lkDa was rat collagen type I alpha 2. According to the above results, it was considered that cadmium degraded the collagen fibers within the wall of small blood vessels in seminiferous tubules and interstitial tissues and disrupted vascular walls, which resulted hemorrhagic necrosis, death of all the spermatogenic cells, and the death of interstitial cells and fibroblastic cells.

극 저 에너지 비소 및 붕소 이온 주입시 효과적인 분자 역학 방법을 사용한 불순물 분포와 격자 결함 분포 예측

황호정,강정원 중앙대학교 기술과학연구소 1998 기술과학연구소 논문집 Vol.28 No.-

본 논문은 분자 역학 방법(molecular dynamics method)을 사용하여 극 저 에너지 비소 및 붕소 이온 주입의 원자단위에 관한 연구로서 국부 격자결함 축적 모델(local damage accumulation model)을 제안하고, 이를 사용한 이온 주입 시뮬레이션 결과를 보여주고 있다. 국부 격자결함 확률 축적 함수는 각 단위 셀에 축적된 에너지, 이온빔 전류, 기판 물질, 주입 이온과 이온 발생 순서 등으로 구성되어 있다. 시뮬레이션 결과는 SIMS 측정치 및 다른 분자 역학 시뮬레이션과 잘 일치한다. 격자결함을 고려하지 않는 MDRANGE는 격자 결함으로 인한 채널링 억제 효과가 나타나지 않기 때문에 불순물 분포의 꼬리 부분에서 많은 차이를 보였다. 또한 국부 격자결함 축적 모델을 사용한 경우와 이를 고려하지 않은 경우의 불순물과 격자결함에 관한 2차원 분포를 계산하여 국부적으로 축적된 격자결함이 이온의 진행에 미치는 영향에 관하여 연구하였다. We have investigated the effects of atomic dynamics for ultra-low energy As and B ion implant using highly efficient molecular dynamics(MD) scheme. We simulate ion implantation by MD simulation using energetic particle approximation method and local damage accumulation model proposed in the paper. Local damages accumulation probability function is composed of deposited energy in a unit cell, implant dose rate, target material, projectile atom, and recoil event number. The simulated results were good agreement with the experimental and other simulated results. The MDRANGE results considering no damages were different from SIMS data in the tail region. Using the local damage accumulation model and energetic particle approximation method, we simulated 2 dimensional dopant and damage profiles.

치은연하 파절로 치조골 소실을 동반한 상악측절치에서 orthodontic extrusive remodeling후 임플란트 식립을 통한 심미수복 : 증례보고

황수연,손원준,한영철,배광식,백승호,이우철,금기연 大韓齒科保存學會 2008 Restorative Dentistry & Endodontics Vol.33 No.1

심미적으로 중요한 전치부에서 단일 치아 임플란트를 이용한 보철수복은 임상의에게 새로운 도전과제 중의 하나가 되었다. 그러나 전치부에서 single-unit implant는 식립할 부위의 치조골 상태가 양호해야 하는데 치은연하 파절로 인해 치아 주위에 골 손실이 있는 경우 immediate implant는 심미적으로 문제를 야기할 수 있다. 따라서 본 증례는 "orthodontic extrusive remodeling"을 통해 파절치와 주위 조직을 교정적으로 정출시켜 임플란트 식립을 위한 연조직과 경조직을 증대시킨 후 임플란트 식립을 통해 상악측절치에서 성공적인 심미수복을 이룬 증례에 관한 것이다. The treatment of esthetic areas with single-tooth implants represents a new challenge for the clinician. In 1993, a modification of the forced eruption technique, called "orthodontic extrusive remodelling" was proposed as a way to augment both soft- and hard-tissue profiles at potential implant sites. This case report describes augmentation of the coronal soft and hard tissues around a fractured maxillary lateral incisor associated with alveolar bone loss, which was achieved by forced orthodontic extrusion before implant placement. Through these procedures we could reconstruct esthetics and function in a hopeless tooth diagnosed with subgingival root fracture by trauma.

개에서 발생한 척수질환에 대한 추적조사(70예)

황현민,이재연,지현철,이영원,최호정,박성준,김명철,정성목 忠南大學校 獸醫科大學 附設 動物醫科學硏究所 2006 動物醫科學硏究誌 Vol.14 No.-

This study was performed to evaluate the prevalence of spinal disorders in dogs, as well as their breed, age, gender and body weight distributions. Seventy cases of caine spinal disoreders presented in the period 2001 and 2006 were reviewed. The diagnosis was obtained by survey radiographs, myelogram, CSF analysis, CT and MRI. The most frequent breed was Maltese(15 cases), and followed by Yorkshire Terrier (10 cases), Pekingese (9 cases). Canine spinal disorders occurred from 7 month to 17 year old dog, mean age was 5.3±3.7 year-old. Canine spinal disorders occurred more often in females(59.7%) than males. Mean body weight was 5.87±7.02 kg. Degenerative (39 cases, 43.3%) and anomalous (24 cases, 26.7%) disorders were dominant in 90 specific disease distribution. This results can be a reference data for the further study.

원자력 사고 중 핵종의 건·습침적에 따른 농작물 오염 영향

황원태,김은한,서경석,한문희,최용호,이창우 대한방사선 방어학회 2002 방사선방어학회지 Vol.27 No.3

핵종의 지표 침적 모델의 고찰과 함께 방사성물질의 공기중 농도로부터 건침적 뿐 아니라 습침적에 따른 농작물 오염 영향을 분석, 고찰하였다. 이를 위해 방사성물질의 지표 침적량으로부터 농작물의 오염을 평가하는 기존 동적 섭식경로모델을 공기중 농도 또는 지표 침적량으로부터 평가할 수 있도록 개선하였다. 평가결과, 방사성물질의 지표 침적량은 습침적에 의한 영향이 건침적에 의한 영향보다 뚜렷이 높으나, 농작물의 오염정도는 핵종, 강우율 등에 따라 다르게 나타났다. 이러한 현상은 방사성물질의 지표 침적과 농작물에로의 차단중 어느 과정이 농작물 오염에 보다 지배적으로 작용하는가에 기인한다. Combined with deposition model onto the ground of radionuclides, the influence of radioactive contamination to agricultural products was analyzed due to wet deposition as well as dry deposition from radioactive air concentration during a nuclear emergency. The previous dynamic food chain model, in which initial input parameter is only radionuclide concentrations on the ground, was improved for the evaluating of radioactive contamination to agricultural products from either radionuclide concentrations in air or radionuclide concentrations on the ground. As the results, in case of deposition onto the ground, wet deposition was more dominant process than dry deposition. While the contamination levels of agricultural products were dependent on the a variety of factors such as radionuclides and rainfall rate. It means that the contamination levels of agricultural products are determined from which is more dominant process between deposition on the ground and interception onto agricultural plants.

김치 추출물에 의한 Aflatoxin B_1의 돌연변이 억제 효과

황승영,허영미,최영현,이숙희,박건영,이원호 부산대학교 유전공학연구소 1997 분자생물학 연구보 Vol.13 No.-

The inhibitory effects of Kimchi extracts on the mutagenicity induced by aflatoxin B₁(AFB₁) in Salmonella and Drosophila assay systems were studied. The kimchi extracts had inhibitory activity for His^+ to His^+ reverse-mutations induced by AFB₁acting on S. typhimurium TA98. A similar inhibitory effect was detected in somatic cell mutation assaying system of D. melanogaster. In Drosophila wing hair spot test, mutant clone frequency induced by AFB₁was consideranly inhibited by the kimchi extracts. These facts suggest that kimchi rxtracts can inhibit gene mutation, deletion, mititic chromosomal recombination and suppress the formation of cancer and mutation by DNA damage.

Interleukin-2가 Mouse 자궁선상피세포의 미세구조에 미치는 영향

황규성,김원규,이규식,정호삼 한양대학교 의과대학 1990 한양의대 학술지 Vol.10 No.1

It is well known that the endometrium of uterus changes histologically during the estrous cycle in rodents. Interleukin-2, a kind of lymphokine produced by the T lymphocyte activated by antigen or mitogen, induces antitumor effect by stimulating the proliferation of helper and cytotoxic T lymphocytes, augmenting the cytolytic activities of the cytotoxic T lymphocyte and differentiating a precursor cell into a lymphokine-activated killer cel in vivo. Although interleukin-2 suppresses the metastasis of the malignant tumor into the adjacent organs and the tumor itself, it develops many side effects including fever, chills and decreased hepatic functions. Interleukin-2 also causes increase of capillary permeability with weight gain, pulmonary edema and ascites. In this experiment, the author studied the effect of interleukin-2 on the mouse uterine glandular cells, observing electron microscopically the changes in cytoplasmic organelles of uterine glandular epithelial cells in mice. Totals of 20 healthy female mice, DDY strain, weighing about 20 gm and exhibiting normal estrous cycle, were used as experimental animals were injected with 2 million units of interleukin-2 diluted in 0.2ml distilled water per kg of body weight and with 0.2ml of normal saline per kg of body weight in the control group for 5 days. And animals were sacrificed at 5th day after administration of interleukin-2. The specimens obtained from te corpus uteri were pre-fixed in 2% glutaradehyde-2.5% paraformaldehyde buffered in Millonig's phosphate solution (pH 7.2) and post-fixed in the 1% osmium tetroxide. After dehydration the specimens were embedded in Epon 812. Ultrathin sections, 600-800A in thickness, were made and double stained with uranyl acetate and lead citrate. And these preparations were observed with the electron microscope. The results obtained were as follows. 1. Microvilli were reduced and microfilaments in microvilli were degenerated. 2. The pronounced dilatation, sacculation and fragmentation of the cisternae of rough endoplasmic reticulum was associated with detachment of the membrane-bound ribosomes. 3. The formation of secondary lysosomes such as autophagic vacuoies and multivesicular bodies were observed. 4. Cristae of the some mitochondria were arranged irregularly and dissociated. Consequently, the results obtained in the present study suggest that interleukin-2 appears to be cytotoxic to the uterine glandular cells of the mouse and induces the degenerative changes of the uterine glandular cells.