• Title/Summary/Keyword: Cu,Zn-superoxide dismutase (SOD1)

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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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    • v.27 no.2
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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.

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

  • Song, Jeong-Sup;Kim, Chi-Hong;Kwon, Soon-Seog;Kim, Young-Kyoon;Kim, Kwan-Hyoung;Han, Ki-Don;Moon, Hwa-Sik;Park, Sung-Hak
    • Tuberculosis and Respiratory Diseases
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    • v.40 no.2
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    • pp.104-111
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    • 1993
  • Background: Gram-negative bacterial endotoxin induced septicemia is known to be a leading cause in the development of adult respiratory distress syndrome(ARDS). The mechanism of endotoxin induced lung injury is mainly due to the activated neutrophils which injure the capillary endothelial cells by releasing oxidant radical and resulted in pulmonary edema. We studied the change of antioxidant enzyme in the case of large or small, intermittant dose of endotoxin infused rat lungs. Methods: Endotoxin was given to the rat through the peritoneal cavity in the dose of 7 mg/kg body weight in the large dose group and 1 mg/kg for 10 days in the small dose group. Bronchoalveolar lavage (BAL) was done and rats were killed at 6, 12, 24 hours after single endotoxin injection in the large dose group and 3, 7, 10 days after daily endotoxin injection for 10 days in the small dose group. The lungs were perfused with normal saline through the pulmonary artery to remove the blood and were homogenized in 5 volume of 50 mM potassium phosphate buffer containing 0.1 mM EDTA. After centrifuging at 100,000 g for 60 minute, the supernatent was removed and stored at $-70^{\circ}C$ until measuring for superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) and protein. Results: We observed the following results. 1) The lung wet/dry weight ratio and albumin concentration in the BAL fluids were increased to peak at 12 hours and neutrophil number in the BAL fluids were peak at 6 hours after endotoxin injection in the large dose group. 2) Cu, Zn SOD (IU/mg protein) was significantly decreased after 6, 12 hours after endotoxin injection in the large dose group. 3) There were no singnificant change in the level of Mn SOD, catalase, GSH-Px after endotoxin injection in both groups. Conclusion: Endotoxin in the large dose group produced the acute pulmonary edema and decreased the Cu, Zn SOD in the lung tissue after injecting endotoxin at 6 and 12 hours. These phenomenon may be due to the cell membrane damage by endotoxin. Further research would be necessary whther giving SOD by intratracheal route or method to increase the synthesis of SOD may lessen the acute lung injury by endotoxin.

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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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    • v.9 no.6
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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.

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

  • 이영구;손형옥;임흥빈;이동욱;박준영
    • Journal of the Korean Society of Tobacco Science
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    • v.15 no.1
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    • pp.3-14
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    • 1993
  • Oxidants in environment or cigarette smoke are known to be implicated in the oxidative damages of pulmonary system. Such cellular damages are prevented by the presence of adequate levels of antioxidants in the tissue. In the present study, we investigated the influences of smoking duration and concentration of smoke on lung antioxidant defense in rats. Subchronic exposure of rats to smoke generated from 6 cigarettes per day for 90 days caused the activities of catalase and superoxide dismutase (SOD) to increase. However, glutathione peroxidase (GP-Xase) was not significantly changed. Total sulfhydryl compounds (Total-SH) in the lung homogenates from the rats inhaled with cigarette smoke for 15 days was decreased by 44% , thereafter it was returned to the level of normal rats. On the contrary, when rats were daily exposed to a different concentration of smoke generated from 1 to 20 cigarettes per day for 15 days, the activity of catalase was increased gradually with dose, but total SOD activity was increased only in the rats of low dose groups less than 5 cigarettes. Three types of SOD (one Cu, Zn-SOD with pI 4.9, and two Zn-SOD with pI 4.7 and 7.9)were detected in the lung homogenates and Zn-SOD with pI 4.7 was the major and cigarette-smoke inducible form. These results indicate that the protection of lung against oxidants from cigarette smoke seems to be accomplished by the induction of catalase and SOD, especially a cyanide resistant Zn-SOD with pI 4.f, following the consumption of antioxidants such as GSH in the beginning of inhalation period.

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

  • 최진호;김대익;박수현;김정민;백영호;이희삼;류강성
    • Journal of Life Science
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    • v.10 no.5
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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

  • Park, Yeong-Sun;Kim, Dong-Yun;Jang, Jae-Cheol;Kim, Dong-Jo;Jeon, Cheol
    • The Journal of Korean Society for Radiation Therapy
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    • v.5 no.1
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    • pp.142-151
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    • 1992
  • Radioprotective effects of a red ginseng extracts on antioxidant enzymes(Superoxide dismutase, catalase and peroxidase) activities relationship to lipid peroxidation were studied in the cytosol fraction of mice liver. The experiments were carried out on Irradiated (5.5 Gy, $^{\60}Co$) and non-irradiated ICR mice after treatment of red ginseng extracts (5.5mg/mouse ; ip), In wholebody irradiated mice, irradiation caused a decrease in the activity of all these enzymes(on Day 21) The activities of SOD, Catalase and Peroxidase of red ginseng extracts treated mice were enhanced by $35.4\%,\;20.2\%$ and $20.1\%$, compared with non-treated mice. The red ginseng extracts led to inhibited increase of malondialdehyde product by ionizing radiation. The enhanced activity of enzymes that removed free radicals generated by radiation and thereby indicate that ginseng probably plays on important role in radioprotective effect.

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

  • Kim, Se-Na;Kim, Min-Seok;Park, Hyun-Suh
    • Journal of Nutrition and Health
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    • v.40 no.2
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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.

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

  • Kim, Byung-Ok;Lee, Kang-Jin;Park, Joo-Cheol
    • Journal of Periodontal and Implant Science
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    • v.24 no.3
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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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