Neuroglobin-overexpressing transgenic mice are resistant to cerebral and myocardial ischemia
Neuroglobin-overexpressing transgenic mice are resistant to cerebral and myocardial ischemia
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DOI：
10.1073/pnas.0607497103
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发表时间：
2006-11-21
影响因子：
11.1
通讯作者：
Greenberg, David A.
中科院分区：
文献类型：
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作者：
Khan, Adil A.;Wang, Yaoming;Greenberg, David A.
神经红蛋白（Ngb）是一种与肌红蛋白和血红蛋白相关的蛋白，但主要在大脑中表达，可由神经元缺氧和脑缺血诱导，并保护神经元免受缺氧或缺血性损伤。我们设计了转基因小鼠，在鸡β -肌动蛋白启动子的控制下过表达小鼠Ngb，导致Ngb在多种细胞类型和多种组织（包括大脑和心脏）中的表达增强。过表达ngb的转基因小鼠与野生型窝鼠相比，大脑中动脉闭塞后的脑梗死体积减少约30%，冠状动脉左前降支闭塞后的心肌梗死体积减少约25%。Ngb过表达与血管内皮细胞内皮型一氧化氮合酶表达增强有关。这些发现扩展了Ngb对细胞保护的先前证据，并提出了直接（实质）和间接（血管舒缩）保护机制。
Neuroglobin (Ngb), a protein related to myoglobin and hemoglobin but expressed predominantly in the brain, is induced by neuronal hypoxia and cerebral ischemia and protects against hypoxic or ischemic neuronal injury. We engineered transgenic mice that overexpress murine Ngb under the control of a chicken beta-actin promoter, resulting in enhanced Ngb expression in multiple cell types and multiple tissues, including brain and heart. In Ngb-overexpressing transgenic mice compared with wild-type littermates, the volume of cerebral infarcts after occlusion of the middle cerebral artery was reduced by approximate to 30%, and the volume of myocardial infarcts produced by occlusion of the left anterior descending coronary artery was reduced by approximate to 25%. Ngb overexpression was associated with enhanced expression of endothelial nitric oxide synthase in vascular endothelial cells. These findings extend prior evidence for cytoprotection by Ngb and suggest both direct (parenchymatous) and indirect (vasomotor) protective mechanisms.