Extracellular but not cytosolic superoxide dismutase protects against oxidant-mediated endothelial dysfunction.
Extracellular but not cytosolic superoxide dismutase protects against oxidant-mediated endothelial dysfunction.
复制标题
DOI：
10.1016/j.redox.2013.04.003
复制
发表时间：
2013
期刊：
影响因子：
11.4
通讯作者：
Miller, Francis J., Jr.
中科院分区：
文献类型：
--
作者：
Foresman, Erin L.;Miller, Francis J., Jr.
超氧化物歧化酶(O2·−)参与心血管疾病的发生发展。O2·−的产生既发生在细胞内，也发生在细胞外。我们推测，细胞内或细胞外超氧化物歧化酶基因转移对O2·−介导的内皮依赖性功能障碍有不同程度的保护作用。将新西兰兔的主动脉环与携带大肠杆菌β-半乳糖苷酶基因的腺病毒(Ad)孵育。活性分析证实，基因转移后24小时，SOD3和SOD1亚型在主动脉中均有功能上的过表达。β-半乳糖苷酶组织化学染色显示基因转移发生在血管内皮细胞和外膜。接下来，血管准备好在含有黄嘌呤的Kreb‘s缓冲液中测量等长张力。加入去甲肾上腺素预收缩后，黄嘌呤氧化物酶减弱血管内皮非依赖性扩张剂乙酰胆碱的松弛作用(ACh，XO组最大松弛33±4%，未加XO组±3%，p<；0.05)，而对非内皮非依赖性扩张剂硝普钠的松弛无明显影响。在XO存在的情况下，AdSOD3可改善血管对ACh的最大松弛(55±2%，p<；0.05与对照组相比)，但AdSOD1对ACh的最大松弛(34±4%)无明显改善。我们的结论是，腺病毒介导的SOD3基因转移，而不是SOD1基因转移，对黄嘌呤/XO介导的内皮功能障碍具有保护作用。这些数据为血管疾病中O2·−产生的位置和酶来源提供了重要的见解。黄嘌呤氧化酶(XO)衍生的O2·−抑制内皮依赖性的松弛。细胞外超氧化物歧化酶减轻氧介导的血管舒缩功能障碍。胞质中超氧化物歧化酶表达的增加不能保护细胞免受XO介导的功能障碍。为了维持·NO的生物利用度，超氧化物歧化酶必须定位在O2·−产生的部位。
Superoxide (O2•−) contributes to the development of cardiovascular disease. Generation of O2•− occurs in both the intracellular and extracellular compartments. We hypothesized that the gene transfer of cytosolic superoxide dismutase (SOD1) or extracellular SOD (SOD3) to blood vessels would differentially protect against O2•−-mediated endothelial-dependent dysfunction. Aortic ring segments from New Zealand rabbits were incubated with adenovirus (Ad) containing the gene for Escherichia coli β-galactosidase, SOD1, or SOD3. Activity assays confirmed functional overexpression of both SOD3 and SOD1 isoforms in aorta 24 h following gene transfer. Histochemical staining for β-galactosidase showed gene transfer occurred in the endothelium and adventitia. Next, vessels were prepared for measurement of isometric tension in Kreb's buffer containing xanthine. After precontraction with phenylephrine, xanthine oxidase impaired relaxation to the endothelium-dependent dilator acetylcholine (ACh, max relaxation 33±4% with XO vs. 64±3% without XO, p<0.05), whereas relaxation to the endothelium-independent dilator sodium nitroprusside was unaffected. In the presence of XO, maximal relaxation to ACh was improved in vessels incubated with AdSOD3 (55±2%, p<0.05 vs. control) but not AdSOD1 (34±4%). We conclude that adenoviral-mediated gene transfer of SOD3, but not SOD1, protects the aorta from xanthine/XO-mediated endothelial dysfunction. These data provide important insight into the location and enzymatic source of O2•− production in vascular disease. Xanthine oxidase (XO)-derived O2•− inhibits endothelium-dependent relaxation. Extracellular SOD alleviates XO-mediated vasomotor dysfunction. Increased expression of cytosolic SOD fails to protect from XO-mediated dysfunction. To maintain •NO bioavailability, SOD must localize to the site of O2•− production.
登录
查看更多内容
影响因子：
15.9
作者：
Rajagopalan, S;Kurz, S;Harrison, DG
通讯作者：
Harrison, DG
DOI：
10.1161/01.atv.0000234921.88489.5c
发表时间：
2006-09-01
影响因子：
8.7
作者：
Chu, Yi;Piper, Robert;Heistad, Donald D.
通讯作者：
Heistad, Donald D.
DOI：
10.1073/pnas.89.8.3362
发表时间：
1992-04-15
影响因子：
11.1
作者：
TERADA, LS;GUIDOT, DM;REPINE, JE
通讯作者：
REPINE, JE
影响因子：
8.3
作者：
Nakane, H;Miller, FJ;Heistad, DD
通讯作者：
Heistad, DD
DOI：
10.1152/ajpendo.1997.273.3.e453
发表时间：
1997-09-01
影响因子：
5.1
作者：
Rattan, V;Sultana, C;Kalra, VK
通讯作者：
Kalra, VK