Nox2 oxidase activity accounts for the oxidative stress and vasomotor dysfunction in mouse cerebral arteries following ischemic stroke.
Nox2 oxidase activity accounts for the oxidative stress and vasomotor dysfunction in mouse cerebral arteries following ischemic stroke.
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DOI：
10.1371/journal.pone.0028393
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Miller AA
中科院分区：
文献类型：
--
作者：
De Silva TM;Brait VH;Drummond GR;Sobey CG;Miller AA
缺血后氧化应激和脑动脉血管功能障碍可能增加认知功能障碍和继发性卒中的可能性。然而，与原发性脑损伤不同，卒中后血管异常的潜在机制尚不清楚。我们测试了是否增强超氧化物依赖性功能障碍发生在小鼠脑循环缺血再灌注后，并评估了Nox 2氧化酶的作用。在雄性C57 B16/J野生型（WT）和Nox 2缺陷型（Nox 2-/-）小鼠中通过大脑中动脉闭塞（MCAO; 0.5小时）诱导脑缺血，然后再灌注（23.5小时）。通过L-012增强的化学发光测量MCA的超氧化物产生。通过对N ω-硝基-L-精氨酸甲酯（L-NAME; 100 µmol/L）的血管收缩反应，在插管和加压的MCA中评估一氧化氮（NO）功能。通过蛋白质印迹法评估脑动脉中Nox 2、硝化标记物3-硝基酪氨酸和白细胞标记物CD 45的表达。缺血-再灌注后，WT小鼠MCA中超氧化物的产生显著增加，但Nox 2-/-小鼠没有。在WT小鼠中，L-NAME诱导的收缩在缺血MCA中减少了1.50%，而缺血再灌注对Nox 2-/-小鼠血管中对L-NAME的反应没有影响。在来自WT小鼠的缺血MCA中，Nox 2和3-硝基酪氨酸的表达是对侧MCA或来自Nox 2-/-小鼠的缺血或对侧血管中的1.4倍。血管CD 45水平没有变化的缺血再灌注。脑缺血再灌注后，小鼠脑动脉内超氧化物产生过多，NO功能受损，出现亚硝化应激。这些异常似乎完全是由于血管Nox 2氧化酶活性增加。
Post-ischemic oxidative stress and vasomotor dysfunction in cerebral arteries may increase the likelihood of cognitive impairment and secondary stroke. However, the underlying mechanisms of post-stroke vascular abnormalities, as distinct from those causing primary brain injury, are poorly understood. We tested whether augmented superoxide-dependent dysfunction occurs in the mouse cerebral circulation following ischemia-reperfusion, and evaluated the role of Nox2 oxidase. Cerebral ischemia was induced in male C57Bl6/J wild-type (WT) and Nox2-deficient (Nox2-/-) mice by middle cerebral artery occlusion (MCAO; 0.5 h), followed by reperfusion (23.5 h). Superoxide production by MCA was measured by L-012-enhanced chemiluminescence. Nitric oxide (NO) function was assessed in cannulated and pressurized MCA via the vasoconstrictor response to N ω-nitro-L-arginine methyl ester (L-NAME; 100 µmol/L). Expression of Nox2, the nitration marker 3-nitrotyrosine, and leukocyte marker CD45 was assessed in cerebral arteries by Western blotting. Following ischemia-reperfusion, superoxide production was markedly increased in the MCA of WT, but not Nox2-/- mice. In WT mice, L-NAME-induced constriction was reduced by ∼50% in ischemic MCA, whereas ischemia-reperfusion had no effect on responses to L-NAME in vessels from Nox2-/- mice. In ischemic MCA from WT mice, expression of Nox2 and 3-nitrotyrosine were ∼1.4-fold higher than in the contralateral MCA, or in ischemic or contralateral vessels from Nox2-/- mice. Vascular CD45 levels were unchanged by ischemia-reperfusion. Excessive superoxide production, impaired NO function and nitrosative stress occur in mouse cerebral arteries after ischemia-reperfusion. These abnormalities appear to be exclusively due to increased activity of vascular Nox2 oxidase.
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影响因子：
20.1
作者：
Ishikawa, M;Stokes, KY;Granger, DN
通讯作者：
Granger, DN
影响因子：
8.3
作者：
Miller, Alyson A.;Drummond, Grant R.;Sobey, Christopher G.
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Sobey, Christopher G.
影响因子：
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Brandes, Ralf P.
影响因子：
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作者：
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通讯作者：
Sobey, Christopher G.
影响因子：
--
作者：
MAYHAN, WG;AMUNDSEN, SM;HEISTAD, DD
通讯作者：
HEISTAD, DD