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.

조혈모세포이식술이 골수기질세포의 기원 및 조골세포로의 증식 및 분화에 미치는 효과

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

말쥐치 가공중 향기성분에 관하여

이종호,최병대,이강호,이근태,김태수 國立統營水産專門大學 附設 水産科學硏究所 1989 수산과학연구소보고 Vol.1 No.-

쥐치의 향기성분을 동정하기 위하여 Likerson형의 연속증류추출 및 탄산가스추출법을 이용하여 휘발성 성분을 동정하였다. 그 결과 중성획분에서 55 성분, pherol성획분에서 4 성분, 염기성획분에서 13 성분 및 ㅅ산성획분에서 10 성분이 분리·동정되었고 중성획분에서는 가열·배소 후 propanol, butanol, octanol, dodecanol등의 alcoholfb 그리고 pentanal, hexanal, 2-methyl-l-propanal, heptenal등의 aldehyde의 함량이 크게 증가하여 flavor 형성에 크게 기여할 것으로 생각되어 진다. 분리·동정된 phenol류는 분자량(m/e) 100~160 정도로 나타났으며, 염기성획분에서는 2-methylpyrazine, 2,5-dimethylpyrazine, 2-ethyl=3,5-dimethylpyrazine 등과 2-methylpyridine등이 동정되었다. 이들과 함께 중성획부에서 동정된 furan류가 가열온도의 증가와 함께 그 함량이 증가하였다. 산성획분에서는 배소시료 구분에서 isoaproic acid 및 caproic acid의 함량이 많았다. Volatile compounds were collected by simultaneous distillation extraction and carbon dioxide method, and analyzed by GC and GC-MS. The neutral fraction obtained from the whole steam volatile concentrate 55 kinds of components, phenolic fraction had 4 kinds of components, basic fraction had 13 kinds of components and 10 kinds of components were in acidic fraction. Alcohols, propanols, butanols, octanols, dodecanols etc. and aldehydes, pentanals, hexanal, 2-methyl-1-propanal, heptenal etc. were highly increased after boiled and roasted. And these compounds were contributed to formation of filefish flavor. The molecular ion peak of phenolic fraction was generally appeared in the range 100 to about 160. From the basic fraction, 2-methylpyrazine, 2,5-dimethylpyrazine, 2-ethyl-3,5-dimethylpyrazine and 2-methylpyridine were identified. The contents of basic compounds and furans obtained from the neutral fraction were increased at the higher heating temperature. The flavor of acidic fraction was influenced by the low molecular as isovaleric and valeric acid.

조구등(釣鉤藤)의 4-VO로 유발한 흰쥐뇌허혈에 대한 신경방어효과

李仁煥,林康鉉,李鍾錫,石庚浩,安德均,朴虎君,김頀哲 대한본초학회 1999 大韓本草學會誌 Vol.14 No.2

Uncariae Ramulus et Uncus(UR, ???) has sweet in flavour and slightly cold in property, acting on the liver and pericardium channels. This drug was described in a medical classic as having the ability to remove "heat", check hyperfunction of the liver and relieve dizziness, tremors, and convulsion, and subdue "endogenous wind". So this study was planned to check the neuroprotective effect of UR on the global ischemia induced by 4-vessel occlusion in Wistar rats. and UR extract was lyophilized after extraction with 70% methanol. We induced 4-vessel occlusion for 10 minutes and reperfused again. The number of CA1 pyramidal neurons were counted after 7 days of reperfusion under the cresyl violet staining. In 4-VO ischemia model, UR showed significantly neuroprotective effects(1,000 and 500 ㎎/㎏ of UR extracts, p<0.05) compared with control group. Each neuroprotective ratio was about 23.0%, 19.0% respectively. Consequently, Uncariae Ramulus et Uncus has neuroprotective effects on the global ischermia induced by 4-vessel occlusion in Wistar rats. So we expect that Uncariae Ramulus et Uncus can be used as a drug for neurodegenerative disease.

신부전이 동반된 당뇨병 환자에서 발생된 침습성 모균증 : 수술과 Liposomal amphotericin B 및 GM-CSF 병합 요법에 의한 성공적인 치험 1예

이원영,오기원,임국희,장재혁,이동건,최정현,강무일,신완식,차봉연,이광우,손호영,강성구 대한화학요법학회 1999 대한화학요법학회지 Vol.17 No.4

저자들은 신부전이 동반된 당뇨병 환자에서 발생된 부비동형 모균증에 대하여 수술과 함께 liposomal amphotericin B 및 GM-CSF의 복합치료를 하여 성공적으로 치료한 1예를 경험하였기에 문헌 고찰과 함께 보고하는 바이다. Mucormycosis (zygomycosis) primarily affects diabetic or immunocompromised patients and typically progresses rapidly, necessitating surgical excision and antifungal therapy with amphotericin B. Large doses of amphotericin B are needed for cure, but it has the risk of causing significant renal toxicity. The recent development of liposomal amphotericin B allows antifungal therapy to be administered with potentially improved efficacy and reduced nephrotoxicity. We have experienced a case of paranasal mucormycosis successfully treated with surgery, liposomal amphotericin B and GM-CSF. A 59-year-old male suffering from diabetes mellitus for 6 years was admitted with pain at left maxillary area. He was diagnosed as mucormycosis after cytologic exam on the necrotic nasal mucosa, which showed typical hyphae. He have had diabetic nephropathy with macroproteinuria and had rapidly rising serum creatinine levels with the amphotericin B treatment: creatinine levels reverted to basal level with the use of liposomal amphotericin B. Despite surgical excision and continued antifungal therapy, his infection was not effectively controlled. Therefore, GM-CSF was administered additionally to improve phagocytic activity of leukocytes. He was finally cured after receiving a combination of aggressive surgery, liposomal amphotericin B and GM-CSF. To our knowledge, this is the first detailed clinical description of the treatment of mucormycosis with liposomal amphotericin B in Korea.

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.

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

경골 골수강내 금속정 삽입술시 적절한 도입부에 대한 해부학적 분석

강수용,이은우,강기서,이한준,정호중,정평호 대한골절학회 2004 대한골절학회지 Vol.17 No.2

동종골수이식 후 혈당 및 혈중 지질농도의 변화양상 및 관련인자

이원영,강무일,오은숙,오기원,손현식,윤건호,차봉연,이광우,손호영,강성구,신완식,민우성,김춘주 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.24 No.6

연구배경:골수이식은 비교적 젊은 연령의 환자들을 대상으로 하며 면역억제제의 사용기간이 비교적 짧으므로, 주로 고령의 만성 질환 환자에서 시행되는 고형장기이식에서와는 달리 당대사 및 지단백 대사에 있어서 많은 차이점이 있을 것으로 추측된다. 저자들은 전향적 연구를 통하여 골수이식 후 시기별로 혈당 및 혈중지단백 변화 양상을 알아보고 이와 관련된 임상인자들을 규명하고자 하였다. 방법:1998년 10월부터 1999년 8월까지 가톨릭대학교 성모병원에서 동종골수이식을 시행한 환자들 중 43명을 대상으로 이식 전 및 이식 후 1, 2, 3, 4주와 3개월, 6개월에 공복 혈당, 혈중 총 콜레스테롤, 중성지방, 고밀도지단백을 측정하여 골수이식 후 시기별 변화를 관찰하고 여러 임상인자들에 따른 차이를 알아보았다. 결과:1. 공복혈당은 골수이식 수 첫4주 동안 상승하였고 이후 감소하였으나 이식 6개월 시점의 평균 공복혈당은 이식 전보다 유의하게 높게 관찰되었다. 혈중 총 콜레스테롤은 이식 후 1주에 최고치를 형성하였고 이후 기저수준으로 회복되었다가 이식 수 3,6개월에 다시 증가하여 기저치에 비해 유의하게 높았다. 혈중 중성지방은 이식 후 1개월까지 유의하게 증가하였고 이후 감소하여, 3,6개월에는 기저치와 유의한 차이가 관찰되지 않았다. 혈중 고밀도지단백은 이식 후 2,3주에 이식 전보다 유의하게 감소하였고 이후 이식 전 수준으로 회복되었다. 혈중 저밀도지단백은 총 콜레스테롤의 변화와 매우 유사하였다. 2. 골수이식 후 6개월 시점에서 공복 혈당이 126㎎/dL이상인 환자는 7명(16%)이었다. 이들 환자들과 공복혈당 126㎎/dL 미만의 환자 36명을 비교한 결과, 공복혈당이 126㎎/dL 이상인 환자군에서 스테로이드 평균 투여량이 많았고 고밀도지단백이 유의하게 낮았다. 3. 이식편대숙주질환이 발생한 환자는 그렇지 않은 환자보다 이식 후 1, 2, 3주 및 6개월의 총 콜레스테롤이 더 낮았고, 3개월의 공복혈당이 더 높았다. 혈연골수이식 환자군은 비혈연골수이식 환자에 비해 투여된 스테로이드 용량이 더 적음에도 불구하고 이식 후 1, 2, 3주 및 6개월의 총 콜레스테롤 수치가 더 높았다. 스테로이드 고용량 투여군(하루 평균 7.5㎎기준)은 저용량군보다 이식 후 3개월 시점의 공복혈당이 더 높았으나 나머지 시점의 혈당, 혈중 지질농도에 있어서는 유의한 차이가 관찰되지 않았다. 결론:골수이식 후 초기시기에 주로 당 대사 및 지질대사이상이 관찰되며 이는 면역억제제 투여와 관련이 있음을 알 수 있었다. 면역억제제가 고용량 투여되는 합병증 발생 시 이들 대사이상에 관심을 기울여 대처해야 할 것이다. Background: In bone marrow transplantation(BMT), recipients are usually younger and immunosuppressants are open used in shorter period than in solid organ transplantation. Therefore, there might be a difference in glucose and lipid metabolism between BMT and solid organ transplantation. However, the serial changes of metabolic parameters following BMT have not been studied. Therefore, the aim of this study is to investigate the serial changes of blood glucose, lipids and the putative factors that are related with these changes after BMT. Methods: We have prospectively investigated 43 patients who underwent allogeneic BMT. Fasting plasma glucose(FPG), total cholesterol, triglyceride and high-density lipoprotein(HDL) were measured before BMT, and at 1, 2, 3, 4, 12 weeks and 6 months after BMT. The serial changes of these metabolic parameters according to clinical factors including type of BMT, mean daily steroid dosage, and occurrence of graft versus host disease (GVHD) were examined. Results: 1. Mean FPG level increased during 4 weeks after BMT and remained above basal value at post-transplant 6 months. Total Cholesterol level was increased during initial 4 weeks after BMT and was above basal value at post-BMT of 3 and 6 months. Triglyceride level was progressively increased during initial 4 weeks after BMT, but returned to basal value there after. HDL-cholesterol level was significantly decreased during initial 4 weeks after BMT, but returned to basal value there after. 2. Patients with FPG above 126 mg/dL and the other patients, the former received larger amounts of daily steroid and had lower HDL-cholesterol level. 3. The changes of metabolic parameters were different according to type of BMT, steroid dose, and occurrence of GVHD. Conclusion: Although there was increase of FPG, TC, TG and decrease of HDL-C during initial 4 weeks after BMT, these metabolic changes recovered slowly thereafter. Immunosuppressants are thought to be associated with these changes. Further observation will be needed for the long-term effect of BMT on metabolic changes(J Kor Diabetes Asso 24:689~698, 2000).

Hydrogen Behavior in Ti-Added Reduced Activation Ferritic-Martensitic Steels

Kang‑Mook Ryu,Dae Geon Lee,Joonoh Moon,Chang‑Hoon Lee,Tae‑Ho Lee,Jae Sang Lee,Dong‑Woo Suh 대한금속·재료학회 2021 METALS AND MATERIALS International Vol.27 No.3

Hydrogen behavior and corresponding mechanical degradation were examined in TaTi-RAFM and EUROFER97 steels. Increased Ta content with Ti addition decelerates the hydrogen diffusion but increases the solubility in the lattice. It ismainly led by the higher fraction of Ta-rich MC carbides and dislocation density in TaTi-RAFM steel. Overall activationenergy of hydrogen trapping of investigated steels is evaluated to be 25.3 ~ 25.6 kJ/mol in the tempered condition. The activationenergy increases to nearly 30 kJ/mol when the steels are re-austenitized and quenched. Higher activation energy withincreased dislocation density indicates that the dislocation provides for trap site with higher activation energy than Ta-richMC carbide. Mechanical degradation by hydrogen with respect to the yield strength, tensile strength and uniform elongationcould not be observed in all investigated steels. The presence of hydrogen only has influence on the loss of post-uniformelongation. For a given charging time, the loss of post-uniform elongation is more remarkable in TaTi-RAFM steel due tothe larger hydrogen uptake.