Up-regulation of Heme oxygenase-1 attenuates brain damage after cerebral ischemia via simultaneous inhibition of superoxide production and preservation of NO bioavailability

被引：53

作者：

Chao, Xiaodong D. ^{[1
]}

Ma, Yihui H. ^{[2
]}

Luo, Peng ^{[2
]}

Cao, Lei ^{[3
]}

Lau, Wayne Bond ^{[5
]}

Zhao, Baocheng C. ^{[4
]}

Han, Feng ^{[2
]}

Liu, Wei ^{[2
]}

Ning, Weidong D. ^{[2
]}

Su, Ning ^{[2
]}

Zhang, Lei ^{[2
]}

Zhu, Jie ^{[2
]}

Fei, Zhou ^{[2
]}

Qu, Yan ^{[2
]}

机构：

[1] Xinjiang Mil Gen Hosp, Dept Neurosurg, Urumqi 830000, Peoples R China

[2] Fourth Mil Med Univ, Xijing Hosp, Dept Neurosurg, Xian 710032, Peoples R China

[3] Xi An Jiao Tong Univ, Coll Med, Xian Cent Hosp, Dept Neurol, Xian 710032, Shaanxi, Peoples R China

[4] Gen Polit Dept Hosp, Healthcare Dept, Beijing 100120, Peoples R China

[5] Thomas Jefferson Univ Hosp, Dept Emergency Med, Philadelphia, PA 19107 USA

来源：

EXPERIMENTAL NEUROLOGY | 2013年 / 239卷

基金：

中国国家自然科学基金;

关键词：

Heme oxygenase-1; MCAO; Oxidative/nitrative stress; NOS; NITRIC-OXIDE SYNTHASE; TRANSIENT FOCAL ISCHEMIA; OXIDATIVE STRESS; NEURONAL INJURY; INDUCTION; RATS; PEROXYNITRITE; CELLS; TETRAHYDROBIOPTERIN; ACCUMULATION;

D O I：

10.1016/j.expneurol.2012.09.020

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Cerebral ischemia exacerbates neuronal death and neurological dysfunction. Evidence supports the involvement of oxidative/nitrative stress in the pathophysiology of cerebral ischemia. Heme oxygenase-1 (HO-1) is a rate-limiting enzyme in heme catabolism, possessing potent anti-oxidant and anti-apoptosis effects. In transgenic mice, HO-1 overproduction is neuroprotective against cerebral ischemia injury, but by unclear mechanisms. The present study determined whether treatment with adenoviral vector overexpressing HO-1 (Ad-HO-1) attenuates post-ischemic brain damage via reduction of oxidative/nitrative stress. After focal cerebral ischemia, Ad-HO-1 reduced lipid peroxidation and protein nitration, decreased infarct volume, and attenuated neurologic deficits. Zinc protoporphyrin IX (ZnPP IX, a specific HO-1 inhibitor) blocked Ad-HO-1 mediated effects against ischemic brain damage. Although Ad-HO-1 slightly reduced ischemic brain NO concentrations, Ad-HO-1 treatment significantly inhibited cerebral expression of iNOS protein expression, without significant effect upon nNOS or eNOS expression compared to vehicle after focal cerebral ischemia. Ad-HO-1 preserved NO bioavailability by increasing eNOS phosphorylation during ischemia compared to vehicle. Together, our results suggest that Ad-HO-1 attenuates post-ischemic brain damage via simultaneous reduction of oxidative/nitrative stress and preservation of NO bioavailability. (c) 2012 Elsevier Inc. All rights reserved.

引用

页码：163 / 169

页数：7

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