Oxygen-glucose deprivation and interleukin-1α trigger the release of perlecan LG3 by cells of neurovascular unit.
Oxygen-glucose deprivation and interleukin-1α trigger the release of perlecan LG3 by cells of neurovascular unit.
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DOI：
10.1111/j.1471-4159.2011.07484.x
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发表时间：
2011-11
影响因子：
4.7
通讯作者：
Bix GJ
中科院分区：
文献类型：
--
作者：
Saini MG;Pinteaux E;Lee B;Bix GJ
作为脑缺血的直接结果，NVU处的细胞面临的两种主要应激是氧-葡萄糖剥夺（OGD）/再灌注和由IL-1上调引起的炎性应激。由于这些压力，串珠素，NVU细胞外基质（ECM）的重要组成部分，是高度蛋白水解。在这里，我们描述了大鼠局灶性脑缺血导致串珠素C-末端生物活性片段LG 3的产生增加。此外，进行NVU细胞的体外研究以定位这种增加的串珠素-LG 3的来源。将神经元、星形胶质细胞、脑内皮细胞和周细胞暴露于OGD/再灌注和IL-1α/β。观察到神经元和周细胞在其培养基中的OGD期间显示出增加的LG 3水平。在体外再灌注过程中，神经元，星形胶质细胞和周细胞显示LG 3水平升高，但仅在暴露于短暂的OGD后。IL-1α和IL-1β处理对NVU细胞有相反的作用。虽然IL-1α增加或对LG 3产生的影响极小或无影响，但在研究的大多数细胞中，高浓度的IL-1β降低了LG 3产生。最后，LG 3被确定为在脑内皮细胞中具有神经保护和抗增殖作用，这表明LG 3在缺血性脑中的产生可能起作用。
Two of the main stresses faced by cells at the NVU as an immediate result of cerebral ischemia are oxygen-glucose deprivation (OGD)/reperfusion and inflammatory stress caused by up regulation of IL-1. As a result of these stresses, perlecan, an important component of the NVU extracellular matrix (ECM), is highly proteolyzed. Here we describe that focal cerebral ischemia in rats results in increased generation of LG3, the c-terminal bioactive fragment of perlecan. Further, in vitro study of the cells of the NVU was performed to locate the source of this increased perlecan-LG3. Neurons, astrocytes, brain endothelial cells and pericytes were exposed to OGD/reperfusion and IL-1α/β. It was observed that neurons and pericytes showed increased levels of LG3 during OGD in their culture media. During in vitro reperfusion, neurons, astrocytes and pericytes showed elevated levels of LG3, but only after exposure to brief durations of OGD. IL-1α and IL-1β treatment tended to have opposite effects on NVU cells. While IL-1α increased or had minimal to no effect on LG3 generation, high concentrations of IL-1β decreased it in most cells studied. Finally, LG3 was determined to be neuroprotective and anti-proliferative in brain endothelial cells, suggesting a possible role for the generation of LG3 in the ischemic brain.
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DOI：
10.1016/s0165-3806(01)00220-6
发表时间：
2001-09-23
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
Chow, J;Ogunshola, O;Madri, JA
通讯作者：
Madri, JA
影响因子：
20.3
作者：
Bix, Gregory;Iozzo, Rex A.;Iozzo, Renato V.
通讯作者：
Iozzo, Renato V.
影响因子：
5.6
作者：
Al Ahmad, A.;Gassmann, M.;Ogunshola, O. O.
通讯作者：
Ogunshola, O. O.
影响因子：
2.9
作者：
Hill, JK;Gunion-Rinker, L;Eckenstein, FP
通讯作者：
Eckenstein, FP
影响因子：
5.3
作者：
Lee, Hsueh-Te;Chang, Ying-Chao;Huang, Chao-Ching
通讯作者：
Huang, Chao-Ching