• 제목/요약/키워드: Cu,Zn-superoxide dismutase (SOD1)

검색결과 140건 처리시간 0.024초

In Vivo Protein Transduction: Delivery of PEP-1-SOD1 Fusion Protein into Myocardium Efficiently Protects against Ischemic Insult

  • Zhang, You-en;Wang, Jia-ning;Tang, Jun-ming;Guo, Ling-yun;Yang, Jian-ye;Huang, Yong-zhang;Tan, Yan;Fu, Shou-zhi;Kong, Xia;Zheng, Fei
    • Molecules and Cells
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    • 제27권2호
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    • pp.159-166
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    • 2009
  • Myocardial ischemia-reperfusion injury is a medical problem occurring as damage to the myocardium following blood flow restoration after a critical period of coronary occlusion. Oxygen free radicals (OFR) are implicated in reperfusion injury after myocardial ischemia. The antioxidant enzyme, Cu, Zn-superoxide dismutase (Cu, Zn-SOD, also called SOD1) is one of the major means by which cells counteract the deleterious effects of OFR after ischemia. Recently, we reported that a PEP-1-SOD1 fusion protein was efficiently delivered into cultured cells and isolated rat hearts with ischemia-reperfusion injury. In the present study, we investigated the protective effects of the PEP-1-SOD1 fusion protein after ischemic insult. Immunofluorescecnce analysis revealed that the expressed and purified PEP-1-SOD1 fusion protein injected into rat tail veins was efficiently transduced into the myocardium with its native protein structure intact. When injected into Sprague-Dawley rat tail veins, the PEP-1-SOD1 fusion protein significantly attenuated myocardial ischemia-reperfusion damage; characterized by improving cardiac function of the left ventricle, decreasing infarct size, reducing the level of malondialdehyde (MDA), decreasing the release of creatine kinase (CK) and lactate dehydrogenase (LDH), and relieving cardiomyocyte apoptosis. These results suggest that the biologically active intact forms of PEP-1-SOD1 fusion protein will provide an efficient strategy for therapeutic delivery in various diseases related to SOD1 or to OFR.

내독소 투여후 쥐의 폐조직내 Antioxidant (Superoxide Dismutase, Catalase, GSH-Peroxidase)의 변화에 대한 연구 (The Change of Antioxidant Enzyme (Superoxide Dismutase, Catalase, Glutathione Peroxidase) in the Endotoxin Infused Rat Lung)

  • 송정섭;김치홍;권순석;김영균;김관형;한기돈;문화식;박성학
    • Tuberculosis and Respiratory Diseases
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    • 제40권2호
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    • pp.104-111
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    • 1993
  • 연구배경 : 그람 음성균의 내독소는 ARDS를 유발하는 제일 흔한 원인으로 알려져 있으며 그 기전중에 내독소에 의해서 폐로의 유입이 증가되고 활성화된 호중구에서 분비하는 산소기가 증가하여 모세혈관 내피세포등에 손상을 입히기 때문이라는 설이 유력하다. 그러한 증가된 산소기를 처리하는 항산화효소가 내독소를 대량 투여하거나 소량 반복투여시 어떻게 변화하는지 알아보고자 본 실험을 하였다. 방법 : 250~300g 되는 쥐에 내독소 대량투여군은 7mg/kg body weight로 내독소를 1회 복강내 주사하였고 소량 반복투여군은 1 mg/kg body weight로 10일간 매일 복강내 주사하였다. 대량투여군은 주사후 6, 12, 24시간후에, 소량 반복투여군은 주사후 3, 7, 10일에 각각 기관지 폐포세척술을 시행하고 살해하였다. 폐동맥을 통하여 생리 식염수를 주입하여 적혈구를 제거한후 양측 폐를 들어내고 무게를 잰후 무게의 5배되는 용량의 50 mM potassium phosphate 완충액하에 3분 간 homogenize시켰다. 이들 $4^{\circ}C$ 에서 60분간 100,000g의 속도로 원심분리하여 상충액을 $-70^{\circ}C$에 보관하였다가 Cu, Zn SOD, Mn SOD, catalase, GSH-Px와 albumin 농도를 측정하였다. 결과: 1) 폐의 wet/dry 무게비 및 기관지 폐포세척액내 albumin 농도는 내독소 대량투여후 12시간에 최고로 증가하였고 기관지 폐포세척액내 호중구는 내독소 대량투여후 6 시간에 최고로 증가하였다. 2) Cu, Zn SOD (IU/mg protein)는 대조군 ($66.7{\pm}26.3$)에 비해 대량투여군에서 6시간후 ($21.86{\pm}5.79$)와 12시간후 ($31.96{\pm}9.54$)에 각각 의의있는 감소를 나타냈으며 소량 반복투여군에서는 큰 변화가 없었다. 3) Mn SOD, catalase, GSH-Px의 양은 대량 또는 소량투여군 모두에서 특별한 변화를 관찰할 수 없었다. 결론: 내독소를 대량투여시 급성 폐부종의 소견과 함께 폐조직내 Cu, Zn SOD가 6시간 및 12시간후에 현저히 감소함을 관찰할 수 있었는데 이러한 현상은 내독소에 의해서 폐의 세포가 손상을 받은 때문으로 생각된다. 따라서 SOD를 외부에서 보충해주거나 폐내에서 합성을 증가시키는 방법으로 급성 폐손상의 진행을 막을수 있는지에 대한 연구가 진행되어야 할 것으로 사료된다.

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Gene Transfer of Cu/ZnSOD to Cerebral Vessels Prevents Subarachnoid Hemorrhage-induced Cerebral Vasospasm

  • Yun, Mi-Ran;Kim, Dong-Eun;Heo, Hye-Jin;Park, Ji-Young;Lee, Ji-Young;Bae, Sun-Sik;Kim, Chi-Dae
    • The Korean Journal of Physiology and Pharmacology
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    • 제9권6호
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    • pp.327-332
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    • 2005
  • The preventive effects of gene transfer of human copper/zinc superoxide dismutase (Cu/ZnSOD) on the development of cerebral vasospasm after subarachnoid hemorrhage (SAH) were examined usin a rat model of SAH. An experimental SAH was produced by injecting autologous arterial blood twice into the cisterna magna, and the changes in the diameter of the middle cerebral artery (MCA) were measured. Rats subjected to SAH exhibited a decreased diameter with an increased wall thickness of MCA that were significantly ameliorated by pretreatment with diphenyleneiodonium (DPI, $10{\mu}M$), an inhibitor of NAD(P)H oxidase. Furthermore, application of recombinant adenovirus ($100{\mu}l$ of $1{\times}10^{10}$ pfu/ml, intracisternally), which encodes human Cu/ZnSOD, 3 days before SAH prevented the development of SAH-induced vasospasm. Our findings demonstrate that SAH-induced cerebral vasospasm is closely related with NAD(P)H oxidase-derived reactive oxygen species, and these alterations can be prevented by the recombinant adenovirus-mediated transfer of human Cu/ZnSOD gene to the cerebral vasculature.

흡연한 흰쥐 폐조직 항산화효소들의 특성 (Characterization of Antioxident Enzymes in the Lung of Rat Exposed to Cigarette Smoke)

  • 이영구;손형옥;임흥빈;이동욱;박준영
    • 한국연초학회지
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    • 제15권1호
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    • pp.3-14
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    • 1993
  • 공기중에 존재하는 여러 산화성 물질들은 호흡기의 손상과 관련이 있는 것으로 알려지고 있으며 이와같은 산화성 물질에 의한 손상은 폐에 존재하는 항산화 물질이나 항산화 효소들에 의해 감소 또는 예방될 수 있다. 저자들은 폐의 항산화방어 기전에 대한 흡연의 영향을 흰쥐에서 관찰하였다. 횐쥐를 6개피의 담배연기에 일일 20분씩 90일간 전신 폭로했을때 조직내의 catalase와 superoxlde dismutase(SOD)의 활성이 유의하게 증가되었다(p<0.05) 그러나 glutathione peroxidase의 활성도는 변화되지 않았고 thiol 화합물의 함량은 흡연 시작후 15일에 44%까지 감소되었으나 그후 정상으로 회복되었다. 한편, 횐쥐를 1, 3, 5, 10 및 20개피의 담배연기에 같은 방법으로 15일간 노출시켰을때, catalase는 개피수에 따라서 증가되었고 총 SOD의 활성도는 5개피 이하에서만 특이하게 증가되었으며 대부분 Zn-SOD이었다. 폐에는 한 종의 Cu, Zn-SOD (pI 4.9)와 CN에 내성이 있는 두종의 Mn-SOD(pI 4.7, pI 7.9)가 존재하였고, 등전점이 4.7인 Zn-SOD가 주된 동위효소로써 흡연에 의해 유도되는 형태였다. 이 결과들은 흡연으로부터 폐의 보호는 초기에는 항산화 물질들의 소모로, 그리고 만성 흡연의 경우는 항산화 효소들의 유도로 이루어지며. 특히 Zn-SOD (pI 4.7)와 catalase가 중요한 역할을 하는 것으로 사료된다.

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간장조직의 활성산소 및 그 제거효소에 미치는 뽕잎 추출물의 영향 (Effects of Mulberry (Morus alba L.) Leaf Extract on Oxygen Radicals and Their Scavenger Enzymes in Liver of SD Rats)

  • 최진호;김대익;박수현;김정민;백영호;이희삼;류강성
    • 생명과학회지
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    • 제10권5호
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    • pp.504-510
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    • 2000
  • This study was designed to investigate the effects of mulberry (Morus alba L.) leaf extract (MLE) on oxygen radicals and their scavenger enzymes in liver membranes of rats. Sprague-Dawley (SD) male rats (160$\pm$10 g) were fed basic diet (control group), and experimental diets (MLE-100 and MLE-300 groups) added 100 and 300 mg/kg BW/day for 6 weeks. Hydroxyl radical (.OH) levels resulted in a significant decreases (15.2% and 18.1%, 5.6% and 8.0%, respectively) in liver mitochondria and microsomes could be not obtained. These are no significant differences in superoxide radical ($O_2$) levels of liver cytosol in MLE-100 and MLE-300 groups compared with control group. Lipid peroxide (LPO) levels were slightly decreased about 13.6% and 6.1% in liver mitochondria and microsomes of MLE-300 group compared with control group. Oxidized protein (OP) levels were remarkably decreased about 16.9% and 27.2% in liver microsomes only of MLE-100 and MLE-300 group compared with control group. Mn-SOD activities in liver mitochondria were remarkably increased (18.2% and 28.7%, respectively) in MLE-100 and MLE-300 groups, and Cu,Zn-SOD activities in liver cytosol were also significantly increased (11.3% and 20.2%, respectively) in MLE-100 and MLE-300 groups compared with control group. Mn-SOD activities in liver mitochondria were remarkably increased (18.2% and 28.7%, respectively) in MLE-100 and MLE-300 groups, and Cu,Zn-SOD activities in liver cytosol were also significantly increased (11.3% and 20.2%, respectively) in MLE-100 and MLE-300 groups compared with control group, but significant difference between GSHPx activities in liver cytosol could be not obtained. These results suggest that anti-aging effect of mulberry leaf extract (MLE) may play a pivotal role in attenuating a various age-related changes.

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감마선 조사전 홍삼 추출물의 투여가 생쥐 간에서의 Superoxide dismutase의 활성과 지질 과산화에 미치는 영향

  • 박영순;김동윤;장재철;김동조;전철
    • 대한방사선치료학회지
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    • 제5권1호
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    • pp.142-151
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    • 1992
  • 생쥐에 5.5mg의 홍삼추출물을 투여한 후 6.5Gy의 감마선을 전신 조사하여 생쥐 간에서의 항산화 효소들(Superoxide dismutase, Catalase, Peroxidase)의 활성도와 지질 과산화 수준의 변화를 측정 비교하여 이들의 상호 관련성과 인삼이 방사선 장해에 미치는 영향을 검토하였다. 방사선 조사로 인하여 SOD, Catalase 그리고 Peroxidase의 활성은 계속적으로 감소하였으나 홍삼추출물 투여군은 방사선 조사 후 21일에 생리적 식염수 투여군보다 Cu, Zn-SOD($40.7\%$), Mn SOD($26.9\%$), Catalase($20.0\%$) 그리고 Peroxidase($20.1\%$)의 활성이 증가되었으며, 또한 방사선 조사로 인하여 상승되는 지질 과산화의 함량이 억제되었다($70.5\%$). 이러한 결과는 인삼 성분이 방사선 조사로 인하여 생성이 촉진된 free radicals를 제거시킴으로서 지질 과산화물의 생성을 억제시켰거나 방사선에 의하여 손상된 기관들의 회복능력을 강화시킨 결과로 보이며 이는 인삼이 방사선 장해에 대하여 회복 또는 방호효과도 있음을 보여 주는 것이라 생각된다.

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식이에 첨가한 Conjugated Linoleic Acid (CLA)가 만성적으로 알코올을 섭취한 쥐에서 간조직의 항산화 체계에 미치는 영향 (Effects of Dietary Conjugated Linoleic Acid (CLA) on Antioxidant System in the Liver of Chronically Ethanol-Treated Rats)

  • 김세나;김민석;박현서
    • Journal of Nutrition and Health
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    • 제40권2호
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    • pp.105-110
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    • 2007
  • The study was designed to observe antioxidant activities of conjugated linoleic acid (CLA) by determining antioxidant enzyme protein levels [cytochrome P4502 El (CYP2E1), Copper, Zinc-superoxide dismutase (CuZn-SOD), glutathione peroxidase (CSH-Px), glutathione S-transferase (GST)] by Western blot analysis and the levels of ${\alpha}$-tocopherol and 2-thiobarbituric acid reactive substances (TBARS) in the liver of chronically ethanol-treated rats. Sixty Sprague Dawley male rats were divided into 3 groups (Control, EtOH, EtOH+CLA). All rats were fed Lieber-DeCarli liquid diet for 4 weeks by pair-feeding against the EtOH group. The liquid diet was supplemented with 1.77g CLA mixture per kg diet in the EtOH+CLA group. Isocaloric maltose dextrin was added in replace of 50g ethanol (36%kcal) for the Control group. Ethanol ingestion significantly increased the levels of CYP2E1 protein and TBARS, but significantly reduced CuZn-SOD protein level and increased GST protein level. There was no significant effect on the level of GSH-Px protein and ${\alpha}$-tocopherol in the liver by ethanol. CLA supplementation with ethanol significantly increased the levels of CuZn-SOD, GSH-Px and GST and also significantly attenuated TBARS level, whereas there was no significant effect on the levels of CYP2E1 protein and ${\alpha}$-tocopherol by CLA. Overall, the CLA supplemented to ethanol could significantly increase the levels of CuZn-SOD, GSH-Px and GST proteins and reduce the level of TBARS in the liver of chronically ethanol-treated rats.

당뇨환자의 치은조직내 Superoxide Dismutase와 Catalase의 활성도에 관한 실험적 연구 (AN EXPERIMENTAL STUDY ON SUPEROXIDE DISMUTASE- AND CATALASE- ACTIVITY IN GINGIVAL TISSUES IN DIABETIC PATIENTS)

  • 김병옥;이강진;박주철
    • Journal of Periodontal and Implant Science
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    • 제24권3호
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    • pp.597-606
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    • 1994
  • Oxygen derived radicals($O_2\;^-$, $H_2O_2$, and $OH^-$) are thought to play a role in a lot of human diseases. And it has been believed that antioxidant enzymes such as superoxide dismutase(SOD) and catalase could protect the tissues from damage resulting from the oxygen derived free radicals. The purpose of this study was performed to investigate the activity of the SOD(CuZn- and Mn-SOD) and catalase in inflammatory gingival tissues and the correlation between boold glucose level and antioxidants and age in non-insulin dependent diabetes mellitus(NI- DDM) patients. For this study, the patients were classified into normal, inflammatory, and diabetic, and ten their papillary bleeding index(PBI) and gingival index were checked. Subjects consisted of 11 healthy patients with no inflammatroy gingiva, 20 adult periodontitis patients, and 8 diabetic patients, aged 33 to 66(average: 44.62). The blood glucose level of diabetic group was ranged from 120ml/dl to 160ml/dl(physical status 0 : averge : 135.67ml/dl). Gingival tissues were surgically obtained from the patients during periodontal surgery, extraction, and clinical corwn lenghening procedure. The activity of CuZn and Mn- SOD and catalase in the gingival tissues was measured by using UV-spectrophotometer by the same methods that Crapo et al. And Aebi did, respectively. The results were as follows : 1. The Mn-SOD activity was significantly lower in inflammatory group in comparison to normal group(P<0.05), and the activities of antioxidants in diabetic group were not significant in comparison to normal inflammatory group(P>0.05). 2. The activities of antioxidants showed little variation among individuals of different ages (P>0.05). 3. The higher blood glucose level was, the higher gingival index was(P<0.05). 4. There was no correlation between blood glucoe level and activity of antioxidant in inflammatory gingival tissues of NIDDM patients(P>0.05). In conclusion, these results, within the limits of the present experiment, suggest that the activity of Mn-SOD might reflect the inflammatory status of gingival tissue, and the activity of antioxidants was independent of blood glucose level of diabetic patients in physical status 0.

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