Induction of heme oxygenase-1 protects against podocyte apoptosis under diabetic conditions

Lee, Sang Choel,Han, Seung Hyeok,Li, Jin Ji,Lee, Sun Ha,Jung, Dong-Sub,Kwak, Seung-Jae,Kim, Seung Hye,Kim, Dong Ki,Yoo, Tae-Hyun,Kim, Jin Hyun,Chang, Se-Ho,Han, Dae Suk,Kang, Shin-Wook International Society of Nephrology 2009 Kidney international Vol.76 No.8

Heme oxygenase-1 (HO-1) is an anti-oxidant enzyme normally upregulated in response to oxidant injury. Here we determined the role of HO-1 in podocyte apoptosis in glomeruli of streptozotocin-treated rats and in immortalized mouse podocytes cultured in media containing normal or high glucose. HO-1 expression, its activity, the ratio of Bax/Bcl-2 protein, and active caspase-3 fragments were all significantly higher in isolated glomeruli of diabetic rats and in high glucose–treated podocytes. These increases were inhibited by zinc protoporphyrin treatment of the rats or by HO-1 siRNA treatment of the podocytes in culture. The number of apoptotic cells was also significantly increased in the glomeruli of diabetic rats and in high glucose–treated podocytes. Inhibition of HO-1 accentuated the increase in apoptotic cells both in vivo and in vitro. Our findings suggest that HO-1 expression protects against podocyte apoptosis under diabetic conditions.

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>

골수강내 금속정 고정을 이용한 경골 분절골절의 치료

오형호,김대진 동국대학교 경주대학 1996 東國論集 Vol.15 No.-

최근의 연구들은 경골 분절 골절에 대한 이해와 치료 방법에 대해 많은 향상을 가져왔지만 여전히 경골 분절 골절의 치료는 많은 문제점을 내포하고 있고 종종 만족스럽지 못한 결과를 초래하고 있다. 이는 경골의 분절골절이 대개 고 에너지 손상에 의해 발생하고 주위의 연부 조직에 심각한 손상을 동반하는 경우가 많기 때문이다. 교합성 골수강내 금속정 고정이 경골 분절골절의 일반적 치료방법으로 자리잡고 있는데 이 방법은 장관골 간부 골절에 있어 가장 안정적인 고정을 할수 있고 그로 인해 조기 거동과 체중 부하를 허용함으로써 기능회복에 좋은 결과를 초래하기 때문이다. 저자들은 1991년 1월부터 1994년 4월까지 19례의 경골 분절골절에 대해 교합성 골수강내 금속정 고정을 이용해 치료하고 다음과 같은 결과를 얻었다. 1.19례 모두에서 부가적인 치료방법없이 골유함을 얻었다. 2. 9례에서 근위 골절부위는 각형성이 된 채로 고정되면서 골유함이 지연되었다. 이러한 경향은 근위 골절부가 슬관절에 근접할수록 증가하였다. 3. 골수강내 금속정을 이용한 경골 분절골절의 치료에 있어 근위골절부의 정확한 정복과 고정은 난제로 남아 있어 이를 해결할 수 있는 수술방법의 개발이 필요할것으로 사료된다. Locked Intramedullary Nailing for Tibial Segmental Fracture Department of Orthopaedic Surgery, College of Medicine, DongGuk University Hyung Ho Oh M.D., Dae Jin Kim M.D. Although studies in recent years have significantly improved the understanding and treatment of segmental fractures of tibia, the treatment of segmental fractures of the tibia poses many problems and often the results are unsatisfactory, presumably because of the serious damage to surrounding soft tissues that usually occurs by the high energy injury. Interlocking intramedullary nailing has become more popularized because it is one affords of the most stable fixation for shaft fractures of long bones, which enables early mobilization and weight bearing and provide good functional recovery. We experienced nineteen segmental tibial fractures from January 1991 to April 1994.They were treated by interlocking intramedullary nails. The results were as follows. 1. In all the 19 cases, union was achieved without any additional procedures 2. In 9 cases, proximal fracture sites were fixed and united in angulated positions and union was delayed, especially when the proximal fracture site was close to the knee joint. 3. On managing segmental fractures of tibia with intramedullary nailing, proximal fracture site seems to have more difficulties in accurate reduction and fixation, so operative technical innovation and development in the fixation device seems to be necessary.

Antioxidant and hepatoprotective effects of Korean ginseng extract GS-KG9 in a D-galactosamine-induced liver damage animal model

Yun Ho Jo,Hwan Lee,Myeong Hwan Oh,Gyeong Hee Lee,You Jin Lee,Ji Sun Lee,Min Jung Kim,Won Yong Kim,Jin Seong Kim,Dae Seok Yoo,Sang Won Cho,Seon Woo Cha,Mi Kyung Pyo 한국영양학회 2020 Nutrition Research and Practice Vol.14 No.4

BACKGROUND/OBJECTIVES: This study was designed to investigate the improvement effect of white ginseng extract (GS-KG9) on D-galactosamine (Ga1N)-induced oxidative stress and liver injury. SUBJECTS/METHODS: Sixty Sprague-Dawley rats were divided into 6 groups. Rats were orally administrated with GS-KG9 (300, 500, or 700 mg/kg) or silymarin (25 mg/kg) for 2 weeks. The rats of the GS-KG9- and silymarin-treated groups and a control group were then intraperitoneally injected Ga1N at a concentration of 650 mg/kg for 4 days. To investigate the protective effect of GS-KG9 against GalN-induced liver injury, blood liver function indicators, anti-oxidative stress indicators, and histopathological features were analyzed. RESULTS: Serum biochemical analysis indicated that GS-KG9 ameliorated the elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in GalN-treated rats. The hepatoprotective effects of GS-KG9 involved enhancing components of the hepatic antioxidant defense system, including glutathione, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). In addition, GS-KG9 treatment inhibited reactive oxygen species (ROS) production induced by GalN treatment in hepatocytes and significantly increased the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins, which are antioxidant proteins. In particular, by histological analyses bases on hematoxylin and eosin, Masson"s trichrome, α-smooth muscle actin, and transforming growth factor-β1 staining, we determined that the administration of 500 mg/kg GS-KG9 inhibited hepatic inflammation and fibrosis due to the excessive accumulation of collagen. CONCLUSIONS: These findings demonstrate that GS-KG9 improves GalN-induced liver inflammation, necrosis, and fibrosis by attenuating oxidative stress. Therefore, GS-KG9 may be considered a useful candidate in the development of a natural preventive agent against liver injury.

로자탄 대 포시노프릴의 고혈압 환자들에서 항고혈압 효과, 안전성 및 내약성의 비교

박대균,이명묵,채인호,이무용,이홍자,김효수,김철호,손대원,오병희,박영배,최윤식 대한순환기학회 1998 Korean Circulation Journal Vol.28 No.1

Characterization of Antihypertensive Angiotensin I-Converting Enzyme Inhibitor from Recombinant E. coli

Kim, Jae-Ho,Jeong, Seung-Chan,Lee, Dae-Hyoung,Lee, Jong-Soo 배재대학교 자연과학연구소 2005 自然科學論文集 Vol.16 No.1

안지오텐신(ACE) 저해제는 항고혈 효과를 갖고 있으므로 오랫동안 고혈압의 예방이나 치료에 이용되어 왔다. 본 연구는 재조합 대장균으로부터 새로운 ACE 저해제를 생산하고 정제하며 나아가 이들이 구조-기능 관P를 규명하기 위해 수행되었다. Saccharomyces cerevisiase의 ACE 저해 펩타이드 유전자를 함유하고 있는 재조합 pGEX-4T-3을 대장균 BL21(DE3)로 형질전환 시켰다. 재조합 pGEX-4T-3을 갖고 있는 대장균 BL21(DE3)로부터 생산된 Glutathione-s 전이효소 (GST) 융합 단백질을 얻어서 그중 ACE저해 펩타이드를 Sephadex G-25 컬럼 크로마토그래피로 정제하였다. 정제된 ACE 저해 펩타이드는 타이로신-아스파틱엑시드-그리신-글리신-발린-패닐알라린-아르기닌-발린-타이로신-트레오닌의 서열을 가진 새로운 decapeptide이었고 ACE에 대하여 경쟁적으로 저해하였다. The angiotensin I-converting enzyme (ACE) inhibitor has anti-hypertensive effects and has long been used as prevention or remedy of hypertension. This study were carried out to produce and purify a new ACE inhibitor from recombinant E. coli and further elucidate its structure-function relationship. Recombinant pGEX-4T-3 containing ACE inhibitory peptide gene of Saccharomyces cerevisiae was transformed into E. coli BL21(DE3). Glutathione-S transferase (GST) fusion protein from E. coli BL21(DE3) harboring the recombinant pGEX-4T-3 was obtained and the ACE inhibitory peptide was purified with Sephadex G-25 column chromatography. The purified ACE inhibitory peptide was a novel decapeptide with sequence Tyr-Asp-Gly-Gly-Val-Phe -Arg-Val-Tyr-Thr which shows very low similarity to the other ACE inhibitory peptide sequence. The purified ACE inhibitor competitively inhibited ACE.

김대건 (안드레아) 신부 얼굴복원

한승호(Seung-Ho Han),박대균(Dae-Kyoon Park),이우영(U-Young Lee),고기석(Ki-Seok Kohl),김희진(Hee-Jin Kim),허경석(Kyung-Seok Hu),남용석(Yong-Seok Nam) 대한체질인류학회 2001 대한체질인류학회지 Vol.14 No.3

본 작업은 서울대교구 명동성당에서 가툴릭의대에 우리나라 최초의 신부인 김대건 신부의 얼굴복원작 업을 의뢰해 1999년 9월부터 약15개월에 걸쳐 북원작업을 한 것으로 1971년 가툴릭의대 해부학교실에서 조사한 김대건 신부 머리뼈의 직접제측치와 사진 자료를 창조하여 제작하였다 작업의 과정은 머리뼈 계측값이 가장 비슷한 머리뼈를 찾아 복제를 하고 계측치에 맞게 수정한 후, 해부학 실습용 시체에서 직접계측하거나 초음파를 이용하여 간접계측을 한 한국인 얼굴의 표준두께를 적용하여 영굴을 복원하였다. 아울러 한국인에서 조사 한 머리뼈와 얼굴 각 부위의 연관관계자료를 토대로 유토를 이용한 복원작업을 시행하였으며 최종 결과물은 청동을 소재로 흉상을 만들었다. 이와 같은 작업은 법의학분야에서 신원미확인 머리뼈가 발견되었을 때 얼굴복원을 통해 신원을 확인하는 법 의인류학적 연구의 하나로, 한국인의 자료를 토대로 작업한 최초의 영굴복원이며 앞으로 신원확인을 위해 얼굴 을 복원하는 작업에 도움이 될 것으로 생각한다.

8년간(1992~1999) 산업안전보건연구원에 의뢰된 직업병 심의 사례 분석

강성규,김규상,김양호,최정근,안연순,진영우,최병순,양정선,김은아,채창호,최용휴,김대성,박정선,정호근 대한산업의학회 2000 대한직업환경의학회지 Vol.12 No.2

Objectives : Pneumoconisis and noise-induced hearing loss (NIHL) have been reported as main occupational diseases by the Special Health Examination. The Industrial Accident Compensation Insurance has reported various work-related diseases, however, these two diseases occupied almost a half of compensated cases. Therefore, it was not well known about the status of occupational diseases other than pneumoconiosis, NIHL, and cardio-cerebrovascular accident (CVA). This study was conducted to analyze claimed cases as an occupational disease, that was requested to the Korea Industrial Safety and Health Agency (KOSHA). Methods : The local office of the Korea Labor Welfare Corporation (KLWC) has asked the KOSHA for confirmation of claimed cases as an occupational disease. We analyzed 379 cases requested from KLWC, the Ministry of Labor, employers, unions and occupational health agencies from 1992 to 1999. Results : Male was 80.7 % of the requested cases. Their mean age was 42 years old and 75.5 % of them were more than 35 years old. The requested cases were increased rapidly from 25 cases in 1992 to 108 cases in 1999 and the accept rate was 50.7 %. The majority of requested cases were respiratory diseases(22.4%), cancers(18.5%), Neuropsychiatric problems(14.5%), and musculoskeletal problems(13.5%). The accept rate was high in reproductive, respiratory, musculoskeletal and digestive disorders and low in neuropsychiatric, renal and otologic problems and occupational cancers. 73.6% of them were caused by chemical agents, especially 28.5 % were by organic solvents. 67% of them were clinically confirmed at university hospitals. A half of the cases were from KyongIn area, even the request came from the whole country. Conclusions : A claim was common in workers whose age was over 35 years old and exposure history was over 10 years. The respiratory diseases and neuropsychiatric disorders were still main problems in occupational health and occupational cancers was increasing even though its accept rate was not high yet.

Fluoxetine and Sertraline Attenuate Postischemic Brain Injury in Mice

Tae Kyeong Shin,Mi Sun Kang,Ho Youn Lee,Moo Sang Seo,Si Geun Kim,Chi Dae Kim,Won Suk Lee 대한생리학회-대한약리학회 2009 The Korean Journal of Physiology & Pharmacology Vol.13 No.3

This study aimed to investigate whether selective serotonin reuptake inhibitors (SSRIs) attenuate brain injury and facilitate recovery following photothrombotic cortical ischemia in mice. Male ICR mice were anesthetized and systemically administered Rose Bengal. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold light laser. The animals were treated with fluoxetine or sertraline once a day for 14 d starting 1 h after ischemic insult. Treatment with fluoxetine and sertraline significantly reduced the infarct size. The Evans blue extravasation indices of the fluoxetine- and sertraline-treated groups were significantly lower than that of the vehicle group. Treatment with fluoxetine and sertraline shifted the lower limit of the mean arterial blood pressure for cerebral blood flow autoregulation toward normal, and significantly increased the expression of heme oxygenase-1 (HO-1) and hypoxia-inducible factor-1Ձ (HIF-1Ձ) proteins in the ischemic region. These results suggest that SSRIs, such as fluoxetine and sertraline, facilitate recovery following photothrombotic cortical ischemia via enhancement of HO-1 and HIF-1Ձ proteins expression, thereby providing a benefit in therapy of cerebral ischemia.

Fluoxetine and Sertraline Attenuate Postischemic Brain Injury in Mice

Shin, Tae-Kyeong,Kang, Mi-Sun,Lee, Ho-Youn,Seo, Moo-Sang,Kim, Si-Geun,Kim, Chi-Dae,Lee, Won-Suk The Korean Society of Pharmacology 2009 The Korean Journal of Physiology & Pharmacology Vol.13 No.3

This study aimed to investigate whether selective serotonin reuptake inhibitors (SSRIs) attenuate brain injury and facilitate recovery following photothrombotic cortical ischemia in mice. Male ICR mice were anesthetized and systemically administered Rose Bengal. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold light laser. The animals were treated with fluoxetine or sertraline once a day for 14 d starting 1 h after ischemic insult. Treatment with fluoxetine and sertraline significantly reduced the infarct size. The Evans blue extravasation indices of the fluoxetine- and sertraline-treated groups were significantly lower than that of the vehicle group. Treatment with fluoxetine and sertraline shifted the lower limit of the mean arterial blood pressure for cerebral blood flow autoregulation toward normal, and significantly increased the expression of heme oxygenase-1 (HO-1) and hypoxia-inducible factor-1 ${\alpha}$ (HIF-1 ${\alpha}$) proteins in the ischemic region. These results suggest that SSRIs, such as fluoxetine and sertraline, facilitate recovery following photothrombotic cortical ischemia via enhancement of HO-1 and HIF-1 ${\alpha}$ proteins expression, thereby providing a benefit in therapy of cerebral ischemia.