Matrix metalloproteinase-13 is activated and is found in the nucleus of neural cells after cerebral ischemia
Matrix metalloproteinase-13 is activated and is found in the nucleus of neural cells after cerebral ischemia
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DOI：
10.1038/jcbfm.2008.130
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发表时间：
2009-02-01
影响因子：
6.3
通讯作者：
Montaner, Joan
中科院分区：
文献类型：
--
作者：
Cuadrado, Eloy;Rosell, Anna;Montaner, Joan
基质金属蛋白酶（MMPs）参与了缺血性卒中的病理生理过程。在这项研究中，我们研究了在永久性缺血大鼠模型中明胶分解激活的时间过程。我们观察到MMPs的激活早在缺血损伤后30分钟，主要在脑细胞核中。此外，我们还检测了MMP-13在动物模型和脑卒中患者脑组织中的表达。脑缺血90分钟后，MMP-13活性明显升高（P < 0.05）。人梗死/梗死周围组织中活性MMP-13的表达水平也高于对侧（P < 0.05）。有趣的是，我们发现MMP-13共定位与46-diamidino-2-phenyl吲哚信号在人类和大鼠的免疫组化，表明MMP-13的核内定位。免疫组织化学还显示，MMP-13主要由两个物种的神经元产生，但也由大鼠的少突胶质细胞和人类的星形胶质细胞产生。最后，我们进行了大鼠原代神经元培养的氧和葡萄糖剥夺（OGD），我们再现了MMP-13的核转位在体外。细胞核提取物证实OGD后活性MMP-13上调（P < 0.05）。这些结果表明，MMP-13激活和其核转位是缺血刺激的早期结果。
Matrix metalloproteinases ( MMPs) have been implicated in the pathophysiology of ischemic stroke. In this study, we investigated the time course of gelatinolytic activation in a rat model of permanent ischemia. We observed an activation of MMPs as early as 30 mins after the ischemic insult, mainly in the nuclei of brain cells. Besides, we explored MMP-13 expression in brain samples of the animal model and stroke deceased patients. We observed an upregulation of active MMP-13 in rat brains (P < 0.05) after 90 mins of cerebral ischemia. Human infarct/periinfarct samples also showed higher levels of active MMP-13 ( P < 0.05) compared with contralateral ones. Interestingly, we found that MMP-13 colocalized with 46-diamidino-2-phenyl indole signal by immunohistochemistry in both humans and rats, suggesting an intranuclear localization for MMP-13. Immunohistochemistry also revealed that MMP-13 was mainly produced by neurons, in both species, but also by oligodendrocytes in rats, and by astrocytes in humans. Finally we subjected a rat primary neuronal culture to oxygen and glucose deprivation (OGD) and we reproduced the nuclear translocation of MMP-13 in vitro. Nuclear extracts from cells confirmed upregulation of active MMP-13 after OGD (P < 0.05). These results suggest that MMP-13 activation and its nuclear translocation is an early consequence of an ischemic stimulus.