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CoPPIX Protects against TNBS Induced Colitis Through HO-1 Induction
오재민(JaeMin Oh),김진오(JinOh Kim),권영미(Young-Mi Kwon),유민욱(MinWook Rheu),김유림(YuRim Kim),김경숙(KyoungSuk Kim),박승택(SeungTaeck Park),김정중(JeongJoong Kim),최민규(MinKyu Choi),정연태(YeunTai Chung) 대한해부학회 2004 Anatomy & Cell Biology Vol.37 No.5
크론병은 만성 염증성 대장 질환으로 면역반응을 억제함으로써 치료를 시도하고 있으나 치료가 쉽지 않고 치료하는 과정에서 많은 부작용이 생기는 질환이다. 따라서 부작용이 적은 새로운 약제의 개발이 절실한 실정이다. HO-1는 염증 반응을 억제하는 효과가 있다고 알려져 있으나 크론병에서의 그 작용기전은 거의 알려져 있지 않다. 따라서 우리는 크론병 동물모델인 TNBS에 의해 유도된 만성 대장염 모델에서 HO-1의 항 염증 기전을 조사하였다. HO-1의 유도제인 CoPPIX 는 생쥐에서 TNBS에 의한 체중감소, MPO 활성, NF-κB 활성 및 병리, 조직학적 증상 등을 현 저히 개선하였다. 또한 염증의 유지에 중요한 역할을 하는 TNF-α와 IL-1β 등의 발현 역시 억제하였다. 이러한 CoPPIX의 효과들은 HO-1 활성 억제제인 ZnPPIX에 의해 차단되었다. 이상의 결과로 CoPPIX는 HO-1의 유도를 통해서 TNBS에 의해 유도된 만성 대장염의 증상들을 개선시킬 수 있다고 생각되었다. 결론적으로 CoPPIX는 크론병의 치료에 있어 중요한 치료제가 될 수 있다고 생각하며 HO-1은 크론병의 치료에 중요한 target 물질이 될 수 있다고 생각한다. Crohn’s disease is a severe chronic inflammation that is treated mainly by immunosuppression, which often has serious side effects. There is a need to develop new drugs for treating this disease that have few side effects. Heme oxygenase-1 (HO-1) has immunosuppressive properties, but the mechanism of its anti-inflammatory actions is unclear. We investigated the protective effects of HO-1 on trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. An HO-1 inducer, cobalt protoporphyrin IX (CoPPIX), dramatically improved the clinical and histopathological symptoms in TNBS-induced colitis. CoPPIX suppressed tumor necrosis factor-α and interleukin-1β expression and down-regulated the nuclear transcription factor κB activity caused by TNBS. The vehicle copper protoporphyrin IX (CuPPIX) failed to duplicate the protective effects seen with CoPPIX. Moreover, an inhibitor of HO-1 activity-zinc protoporphyrin IX-reversed the protective effects of CoPPIX on TNBS-induced colitis. In conclusion CoPPIX protects against TNBS-induced colonic damage by inducing HO-1, which might be an important target in the treatment of Crohn’s disease.
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6 가 크롬이 백서의 배양섬유모세포에 미치는 세포독성에 관한 연구
강영,반승일,김양일,김형주,정연태 원광대학교 환경과학연구소 1992 環境科學硏究誌 Vol.1 No.1
To investigate the cytotoxicity of Cr^6+, the colorimetric assays of neutral red (NR) and tetrazolium MTT, the measurements of the protein content and the rate of DNA synthesis, and sister chromatid exchange(SCE) analysis were performed in fibroblasts cultured in the medium containing various concentrations of Cr^6+. Electron microscopy of Cr^6+ treated rat fibroblasts was also carried out. The results were as follows ; 1. NR uptake was decreased dose-dependently and NR_90 and NR_50 values of Cr^6+ were 0.2 μM and 1.7μM respectively. 2. Cr^6+ induced the dose-dependent decrease of the activity of mitochondrial succinic dehydrogenase and MTT_90 and MTT_5o valyes were 0.5μM and 5.5 μM respectively. 3, Protein content in rat fibroblasts treated with Cr^6+ decreased dose-dependently. 4. Cr^6+ inhibited DNA synthesis dose-dependently and the rate of DNA synthesis at concentration of Cr^6+ 1.0μM(1.7μM, NR_50) was 33% of the control. 5. Frequency of sister chromatid exchange(SCE) increased dose-dependently and the frequency of sister chromatid exchange at concentration of Cr^6+ 1.0μM was noted to be 8.8 per cell. 6. Light microscopy revealed dose dependent reduction of cell number and decrease in cell size after Cr^6+ treatment. Electron microscopy of cultured fibroblasts treated with Cr^6+ showed dilatation of cisternae of granular endoplasmic reticulum drastic decrease of polyribosomes and increase in number of lysosomes. Above results indicated that Cr^6+ induced severe toxic effect on cultured cell, and suggested that DNA damage by Cr^6+ can be resulted inhibition of cell growth and decrease in cell viability.
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카드뮴이 백서의 배양섬유모세포에 미치는 세포독성에 관한 연구
유태환,반승일,김형주,김양일,정연태 원광대학교 환경과학연구소 1992 環境科學硏究誌 Vol.1 No.1
Present study was carried out to investigate the cytotoxicity of cadmium on cultured rat fibroblasts. The colorimetric assays of neutral red(NR) and tetrazolium MTT, the measurements of total contents of protein, the rated of DNA synthesis, light and electron microscopic studies were performed on the fibroblasts cultured in the media containing various concentrations of cadmium. The results are as follows : 1. The NR and MTT values were increased dose-dependent of cadmium. 2. The MR_90, MR_50, MTT_90 and MTT_50 values of cadmium were 0.2μM, 19.5μM, 1.0μM and 60.0μM, respectively. 3. The total contents of protein at concentrations of cadmium, 0.2μM, 24.5μM were 90% and 50% of the control, respectively. The aspects which decrease the total contents of protein agreed to NR uptake ability. 4. The rates of DNA synthesis at concentrations of cadmium, 5.0μM, 70.0μM were 90% and 50% of the control, and those were 65%, 60% at concentration of NR_50, MTT_50 values, respectively. 5. In light microscopic study, cadmium induced dose-dependent reduction of cell number and decrease in cell size, and election microscopy of cultured fibroblasts treated with cadmium showed dilatation of cisternae of granular endoplasmic reticulum. 6. Cadmium induced the toxic effects on the lysosome and mitochondria at lower concentration than does which didn't affect the rated of DNA synthesis.From the above results, it suggests that the cytotoxic target of cadmium may be cell organelles such as granular endoplasmic reticulum.
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