Protection from reoxygenation injury by inhibition of rac1
Protection from reoxygenation injury by inhibition of rac1
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DOI：
10.1172/jci1830
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发表时间：
1998-05-01
影响因子：
15.9
通讯作者：
Finkel, T
中科院分区：
文献类型：
--
作者：
Kim, KS;Takeda, K;Finkel, T
我们证明，腺病毒介导的基因转移的显性负拉德基因产物（N17 rac 1）抑制细胞内爆发的活性氧（ROS），发生后血管平滑肌细胞复氧。相反，显性负性ras基因（N17 ras）的表达没有影响。用直接氧化应激挑战对照细胞和表达N17 rac 1的细胞，导致细胞内活性氧水平同等增加，随后细胞死亡。这表明N17 rac 1表达似乎阻断有害氧自由基的产生，并且不直接或间接地抑制再氧合期间产生的ROS。N17 rac 1的表达导致在多种细胞类型（包括血管平滑肌细胞、成纤维细胞、内皮细胞和心室肌细胞）中保护免于缺氧/再氧合诱导的细胞死亡。这些结果表明，复氧损伤需要激活的rac蛋白，和rac依赖性途径的抑制可能是一个有用的策略，为预防缺血组织再灌注损伤。
We demonstrate that adenoviral-mediated gene transfer of a dominant negative rad gene product (N17rac1) inhibits the intracellular burst of reactive oxygen species (ROS) that occurs after reoxygenation of vascular smooth muscle cells. In contrast, expression of a dominant negative ras gene (N17ras) had no effect. Challenge of control cells and cells expressing N17rac1 with a direct oxidant stress produced an equivalent increase in intracellular ROS levels and subsequent cell death. This suggests that N17rac1 expression appears to block production of harmful oxygen radicals and does not act directly or indirectly to scavenge ROS generated during reoxygenation. Expression of N17rac1 results in protection from hypoxia/reoxygenation-induced cell death in a variety of cell types including vascular smooth muscle cells, fibroblasts, endothelial cells, and ventricular myocytes. These results suggest that reoxygenation injury requires the activation of rac proteins, and that inhibition of rac-dependent pathways may be a useful strategy for the prevention of reperfusion injury in ischemic tissues.