Brain infarction correlates more closely with acrolein than with reactive oxygen species
Brain infarction correlates more closely with acrolein than with reactive oxygen species
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DOI：
10.1016/j.bbrc.2010.12.107
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发表时间：
2011-01-28
影响因子：
3.1
通讯作者：
Igarashi, Kazuei
中科院分区：
文献类型：
--
作者：
Saiki, Ryotaro;Park, Hyerim;Igarashi, Kazuei
虽然人们认为导致细胞损伤的主要因素是活性氧(ROS)，但我们最近的研究表明，丙烯醛的毒性比ROS更大。因此，利用光化学诱导的血栓模型小鼠，比较了丙烯醛和ROS在脑梗塞期间细胞损伤中的相对重要性。以丙烯醛结合白蛋白、4-羟基壬烯醛结合白蛋白和8-OHdG分别作为丙烯醛和ROS损伤的指标。丙烯醛结合白蛋白的增加远大于HNE结合白蛋白或8-OHdG的增加，这表明在脑梗塞过程中，丙烯醛比ROS更强烈地参与细胞损伤。研究还表明，与DNA或磷脂损伤相比，脑梗塞更容易导致RNA损伤。结果，多胺从RNA中释放出来，丙烯醛从多胺中产生，特别是通过精胺氧化酶从精胺中产生。在精胺含量很低或精胺/精胺N-1-乙酰转移酶活性较高的情况下，用精胺合成酶缺陷的GY小鼠和转谷氨酰胺酶2基因敲除的小鼠，精胺氧化酶可以从精胺产生丙烯醛。(C)2010 Elsevier Inc.保留所有权利。
Although it is thought that the major factor responsible for cell damage is reactive oxygen species (ROS), our recent studies have shown that acrolein is more toxic than ROS. Thus, the relative importance of acrolein and ROS in cell damage during brain infarction was compared using photochemically induced thrombosis model mice. The levels of acrolein-conjugated albumin, and of 4-hydroxynonenal (HNE)-conjugated albumin and 8-OHdG were evaluated as indicators of damage produced by acrolein and ROS, respectively. The increase in acrolein-conjugated albumin was much greater than the increase in HNE-conjugated albumin or 8-OHdG, suggesting that acrolein is more strongly involved in cell damage than ROS during brain infarction. It was also shown that infarction led more readily to RNA damage than to DNA or phospholipid damage. As a consequence, polyamines were released from RNA, and acrolein was produced from polyamines, especially from spermine by spermine oxidase. Production of acrolein from spermine by spermine oxidase was clarified using spermine synthase-deficient Gy mice and transglutaminase 2-knockout mice, in which spermine content is negligible or spermidine/spermine N-1-acetyltransferase activity is elevated. (C) 2010 Elsevier Inc. All rights reserved.