Up-regulation of protein-disulfide isomerase in response to hypoxia/brain ischemia and its protective effect against apoptotic cell death
Up-regulation of protein-disulfide isomerase in response to hypoxia/brain ischemia and its protective effect against apoptotic cell death
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DOI：
10.1074/jbc.275.14.10388
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发表时间：
2000-04-07
影响因子：
4.8
通讯作者：
Nomura, Y
中科院分区：
文献类型：
--
作者：
Tanaka, S;Uehara, T;Nomura, Y
我们分离并鉴定了一种应激蛋白，该蛋白在原代培养的神经胶质细胞中响应缺氧而上调。蛋白质二硫键异构酶（PDI）不仅在体外因神经胶质细胞缺氧而上调，而且在体内因大鼠短暂前脑缺血而上调。为了确定新合成的PDI是否参与对缺血应激的耐受，我进行了两个程序来诱导人神经母细胞瘤SK-N-MC细胞中的PDI基因表达，以及在大鼠中电穿孔能够过表达PDI的表达载体后进行海马内注射。该基因的过度表达分别导致神经母细胞瘤 SK-N-MC 细胞缺氧引起的细胞活力丧失减弱，以及脑缺血大鼠海马 CA1 区 DNA 片段细胞数量减少。这些发现表明，上调的 PDI 可能在抵抗缺血性损伤方面发挥关键作用，并且大脑中这种蛋白质水平的升高可能对预防脑中风产生有益的影响。
We isolated and identified a stress protein that is upregulated in response to hypoxia in primary-cultured glial cells. Protein-disulfide isomerase (PDI) was up-regulated not only by hypoxia in glia in vitro, but also by transient forebrain ischemia in rats in vivo, To determine whether newly synthesized PDI is involved in tolerance to ischemic stress, me carried out two procedures to induce PDI gene expression in human neuroblastoma SK-N-MC cells, as well as intrahippocampal injection following electroporation of an expression vector capable of overexpressing PDI in rats. Overexpression of this gene resulted in attenuation of the loss of cell viability induced by hypoxia in neuroblastoma SK-N-MC cells and a reduction in the number of DNA-fragmented cells in the CA1 area of the hippocampus in brain ischemic rats, respectively. These findings suggest that up-regulated PDI may play a critical role in resistance to ischemic damage, and that the elevation of levels of this protein in the brain may have beneficial effects against brain stroke.