NADPH oxidase-mediated oxidative damage to proteins in the postsynaptic density after transient cerebral ischemia and reperfusion
NADPH oxidase-mediated oxidative damage to proteins in the postsynaptic density after transient cerebral ischemia and reperfusion
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DOI：
10.1016/j.mcn.2011.01.009
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发表时间：
2011-03-01
影响因子：
3.5
通讯作者：
Tanonaka, Kouichi
中科院分区：
文献类型：
--
作者：
Murotomi, Kazutoshi;Takagi, Norio;Tanonaka, Kouichi
NADPH氧化酶是中枢神经系统中超氧化物的重要来源。尽管NADPH氧化酶定位于神经元突触后部位附近，但关于NADPH氧化酶在脑缺血和再灌注后突触中的病理生理作用知之甚少。在本研究中，我们试图确定NADPH氧化酶在氧化损伤突触后密度（PSD）蛋白，这是从大鼠进行短暂的局灶性脑缺血和再灌注的作用。短暂局灶性脑缺血再灌注后，PSD羰基化蛋白的数量增加。这种变化伴随着NADPH氧化酶亚基在PSD的水平增加。给药夹竹桃素，NADPH氧化酶抑制剂，衰减PSD和脑梗死体积的蛋白质羰基化。我们进一步证明，PSD相关蛋白，如神经连接素，N-钙粘蛋白，和SAP 102，在PSD中的量的减少被用夹竹桃麻素治疗所阻止。这些结果表明，脑缺血和再灌注后PSD中NADPH氧化酶的显著激活可能与突触功能的局灶性氧化损伤以及随后的缺血和再灌注诱导的脑损伤的发展有关。(C)2011 Elsevier Inc. All rights reserved.
NADPH oxidase is an important source of superoxide in the central nervous system. Although NADPH oxidase is localized near the postsynaptic site in neurons, little is known about the pathophysiological role of NADPH oxidase in synapses after cerebral ischemia and reperfusion. In the present study, we sought to determine the role of NADPH oxidase in oxidative damage to postsynaptic density (PSD) proteins, which were isolated from rats subjected to transient focal cerebral ischemia and reperfusion. The amounts of carbonylated PSD proteins were increased after transient focal cerebral ischemia and reperfusion. This change was accompanied by an increase in the level of NADPH oxidase subunits in the PSD. The administration of apocynin, an NADPH oxidase inhibitor, attenuated both the protein carbonylation in the PSD and cerebral infarct volume. We further demonstrated that the decreases seen in the amounts of PSD-associated proteins, such as neuroligin, N-cadherin, and SAP102, in the PSD were prevented by treatment with apocynin. These results suggest that pronounced activation of NADPH oxidase in the PSD after cerebral ischemia and reperfusion may be related to the focal oxidative damage to synaptic functions and subsequent development of ischemia and reperfusion-induced cerebral injury. (C) 2011 Elsevier Inc. All rights reserved.