Erythropoietin increases bioavailability of tetrahydrobiopterin and protects cerebral microvasculature against oxidative stress induced by eNOS uncoupling.
Erythropoietin increases bioavailability of tetrahydrobiopterin and protects cerebral microvasculature against oxidative stress induced by eNOS uncoupling.
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DOI：
10.1111/jnc.12824
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发表时间：
2014-11
影响因子：
4.7
通讯作者：
Katusic ZS
中科院分区：
文献类型：
--
作者：
Santhanam AV;d'Uscio LV;Katusic ZS
本研究旨在确定促红细胞生成素（EPO）治疗是否可以保护脑微血管免受内皮型一氧化氮合酶（eNOS）解偶联的病理后果。对野生型和GTP环化水解酶I（GTPCH-I）缺陷型hph 1小鼠给予EPO（1000 U/kg/天，sc，3天）。hph 1小鼠的脑微血管表现出降低BH 4的生物利用度，增加生产的超氧阴离子和受损的内皮一氧化氮（NO）信号。用EPO治疗hph 1小鼠减弱了7，8-二氢生物蝶呤（7，8-BH 2）（BH 4的氧化产物）的水平，并显著增加了BH 4与7，8-BH 2的比率。此外，EPO降低超氧阴离子的水平，增加NO的生物利用度在脑微血管中的hph 1小鼠。BH 4的氧化减弱和eNOS解偶联的抑制被解释为抗氧化蛋白，锰超氧化物歧化酶和过氧化氢酶的表达增加。在hph 1小鼠脑微血管中观察到的EPO保护作用也在暴露于EPO（1 U/ml或10 U/ml; 3天）的GTPCH-I siRNA处理的人脑微血管内皮细胞中观察到。我们的结果表明，EPO可能通过恢复脑微血管内皮中BH 4和内皮NO的生物利用度来保护神经血管单元免受氧化应激。
The present study was designed to determine whether treatment with erythropoietin (EPO) could protect cerebral microvasculature against the pathological consequences of endothelial nitric oxide synthase (eNOS) uncoupling. Wild-type and GTP cyclohydrolase I (GTPCH-I)-deficient hph1 mice were administered EPO (1000 U/kg/day, sc, 3 days). Cerebral microvessels of hph1 mice demonstrated reduced BH4 bioavailability, increased production of superoxide anions and impaired endothelial nitric oxide (NO) signaling. Treatment of hph1 mice with EPO attenuated the levels of 7,8-dihydrobiopterin (7,8-BH2), the oxidized product of BH4, and significantly increased the ratio of BH4 to 7,8-BH2. Moreover, EPO decreased levels of superoxide anions and increased NO bioavailability in cerebral microvessels of hph1 mice. Attenuated oxidation of BH4 and inhibition of eNOS uncoupling were explained by the increased expression of antioxidant proteins, manganese superoxide dismutase and catalase. The protective effects of EPO observed in cerebral microvessels of hph1 mice were also observed in GTPCH-I siRNA-treated human brain microvascular endothelial cells exposed to EPO (1 U/ml or 10 U/ml; 3 days). Our results suggest that EPO might protect the neurovascular unit against oxidative stress by restoring bioavailability of BH4 and endothelial NO in the cerebral microvascular endothelium.
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影响因子：
8.3
作者：
d'Uscio, Livius V.;Katusic, Zvonimir S.
通讯作者：
Katusic, Zvonimir S.
DOI：
10.1152/ajpheart.01215.2003
发表时间：
2004-09-01
影响因子：
4.8
作者：
Andresen, JJ;Faraci, FM;Heistad, DD
通讯作者：
Heistad, DD
影响因子：
3.4
作者：
Jin, Wei;Ming, Xing;Liang, Weibang
通讯作者：
Liang, Weibang
DOI：
10.1161/hypertensionaha.110.150623
发表时间：
2010-04
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
d'Uscio LV;Smith LA;Katusic ZS
通讯作者：
Katusic ZS
DOI：
10.1006/bbrc.1997.6943
发表时间：
1997-07-18
影响因子：
3.1
作者：
Itoh, K;Chiba, T;Nabeshima, Y
通讯作者：
Nabeshima, Y