Induction of manganese superoxide dismutase by glucocorticoids in glomerular cells.
Induction of manganese superoxide dismutase by glucocorticoids in glomerular cells.
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糖皮质激素在肾小球细胞中诱导锰超氧化物歧化酶。
DOI：
10.1038/ki.1994.25
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发表时间：
1994
影响因子：
19.6
通讯作者：
Ichikawa,I
中科院分区：
文献类型：
--
作者：
Yoshioka,T;Kawamura,T;Meyrick,BO;Beckman,JK;Hoover,RL;Yoshida,H;Ichikawa,I
糖皮质激素对肾小球细胞锰超氧化物歧化酶的诱导作用。我们以前的体内研究表明，甲基强的松龙（MP）激活肾小球抗氧化酶，减轻肾小球氧化损伤，包括那些在实验性肾病。本研究探讨了MP诱导的抗氧化酶激活的细胞机制及其对细胞氧化毒性衰减的贡献。当用10 µMMP处理牛肾小球内皮细胞（GECs）时，细胞锰超氧化物歧化酶（MnSOD）（Mn-SOD，3.95 ± 0.33 µ/mg蛋白，M ±SE）和过氧化氢酶（1.64 ± 0.06 k/mg蛋白）活性显著高于对照组（P <0.05）。（P < 0.05）升高至高于对照GEC（分别为2.23 ± 0.43 μ/mg蛋白和1.06 ± 0.09 k/mg蛋白）。当用MP（10 µ M 24小时）预处理的GEC暴露于黄嘌呤（0.1 mM）+黄嘌呤氧化酶（5 mU/ml）4小时时，特定膜脂质过氧化产物（即磷脂酰胆碱和磷脂酰乙醇胺氢过氧化物）的水平保持在未MP处理（黄嘌呤/黄嘌呤氧化酶暴露）对照细胞中测量的水平的10%至25%。此外，暴露于超氧化物生成系统后的细胞损伤程度（通过51 Cr释放评估）在MP处理的细胞中显著减弱（MP未处理的对照组的约50%，N = 6）。因此，MP处理的GECs与MP升高的抗氧化酶活性更能抵抗活性氧代谢产物的毒性作用。探讨了MP诱导Mn-SOD抗氧化酶活性的机制。MP可剂量依赖性地增强牛GECs和大鼠肾小球系膜细胞（GMCs）Mn-SOD mRNA表达。用含有大鼠Mn-SOD基因组DNA的1.2kb片段（转录起始位点的-806 ~+406bp）的荧光素酶报告基因研究了MP对Mn-SOD基因的转录激活作用。当用10 µMMP处理时，用融合基因构建体转染的GMC表现出荧光素酶活性的显著增加（2.6倍）。因此，MP对Mn-SOD的诱导涉及转录激活。融合基因的研究结果表明，在Mn-SOD基因DNA的1.2kb片段内存在一个功能性的糖皮质激素反应元件。
Induction of manganese superoxide dismutase by glucocorticoids in glomerular cells. Our previousin vivostudy demonstrated that methylprednisolone (MP) activates glomerular antioxidant enzymes and attenuates glomerular oxidant injuries, including those in experimental nephrosis. The present study investigates the cellular mechanism of the MP-induced activation of antioxidant enzymes and their contribution to the attenuation of cellular oxidant toxicity. When bovine glomerular endothelial cells (GECs) were treated with 10 µMMP, cellular manganese superoxide dismutase (Mn-SOD, 3.95 ± 0.33 µ/mg protein, M ±SE) and catalase (1.64 ± 0.06 k/mg protein) activities were significantly (P < 0.05) elevated above control GECs (2.23 ± 0.43 µ/mg protein and 1.06 ± 0.09 k/mg protein, respectively). When GECs pretreated with MP (10 µM24 hrs) were exposed to xanthine (0.1 mM) + xanthine oxidase (5 mU/ml) for four hours, levels of specific membrane lipid peroxidation products, that is, phosphatidylcholine- and phosphatidylethanolamine-hydroperoxides, remained at levels 10 to 25% of those measured in non-MP-treated (xanthine/xanthine oxidase-exposed) control cells. Moreover, the degree of cell damage following exposure to the superoxide generating system, assessed by51Cr release, was significantly attenuated in MP-treated cells (≈50% of MP-non-treated controls, N = 6). Thus, MP-treated GECs with elevated antioxidant enzyme activities by MP were more resistant to the toxic effect of reactive oxygen metabolites. The mechanism of antioxidant enzyme induction by MP was studied for Mn-SOD. MP was shown to enhance Mn-SOD mRNA in bovine GECs and rat glomerular mesangial cells (GMCs) in dose-dependent manners. The transcriptional activation of the Mn-SOD gene by MP was studied using a luciferase reporter gene containing a 1.2 kb fragment (-806 to +406 bp of the transcription initiation site) of rat Mn-SOD genomic DNA. GMCs transfected with the fusion gene construct demonstrated a significant increase (2.6-fold) in luciferase activity when treated with 10 µMMP. Therefore, the induction of Mn-SOD by MP involves transcriptional activation. Results with the fusion gene study predict the existence of a functional glucocorticoid responsive element(s) within the 1.2 kb fragment of the Mn-SOD gene DNA.
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DOI：
--
发表时间：
2006
期刊：
総務省統計研修所 リサーチペーパー 第5号
影响因子：
--
作者：
元山 斉;山口 幸三;ryoko Morozumi;美添泰人・荒木万寿夫
通讯作者：
美添泰人・荒木万寿夫
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DOI：
--
发表时间：
1989
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
Schuger,L;Varani,J;Marks,RM;Kunkel,SL;Johnson,KJ;Ward,PA
通讯作者：
Ward,PA
抗氧化酶活性降低是造影剂引起的血容量不足肾损伤的基础。
影响因子：
19.6
作者：
Yoshioka,T;Fogo,A;Beckman,JK
通讯作者：
Beckman,JK
甲基泼尼松龙可使 ANCA 阳性血管炎患者的多晶型物产生的超氧阴离子正常化。
影响因子：
19.6
作者：
D. Macconi;A. F. Zanoli;S. Orisio;L. Longaretti;L. Magrini;S. Rota;A. Radice;C. Pozzi;G. Remuzzi
通讯作者：
G. Remuzzi
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影响因子：
19.6
作者：
Hiraoka-Yoshimoto,M;Higashida,K;Takeda,M;Kawamoto,S;Ichikawa,I;Hoover,RL
通讯作者：
Hoover,RL