Role of PON in anoxia-reoxygenation injury: a Drosophila melanogaster transgenic model.
Role of PON in anoxia-reoxygenation injury: a Drosophila melanogaster transgenic model.
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DOI：
10.1371/journal.pone.0084434
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Comellas AP
中科院分区：
文献类型：
--
作者：
Caraballo JC;Borcherding J;Rector M;Hornick E;Stoltz D;Zabner J;Comellas AP
对氧磷酶1 （PON1）是一种与高密度脂蛋白（HDL）相关的蛋白质，被认为可以防止低密度脂蛋白（LDL）的氧化修饰。这种酶与降低心血管疾病的风险有关。缺氧-再氧化和氧化应激是心脑血管疾病的重要因素。然而，PON1在缺氧-再氧合或缺氧损伤中的作用尚不清楚。我们假设PON1可以防止缺氧再氧化损伤。我们着手确定在黑腹果蝇中PON1的表达是否对缺氧-再氧化（A-R）诱导的损伤有保护作用。野生型（WT）和转基因PON1果蝇暴露于缺氧（100%氮）不同的时间间隔（从1到24小时）。缺氧期后，将果蝇置于室内空气中进行再氧合。然后记录果蝇的活动和存活情况。在缺氧5分钟内，所有果蝇都进入了麻木状态。再充氧后，幸存的果蝇恢复活动有一定的延迟。有趣的是，转基因果蝇比WT更晚从昏迷中恢复过来。与WT相比，PON1转基因果蝇在a - r应激后具有显著的生存优势。无论年龄或饮食限制如何，PON1表达所赋予的保护都存在。此外，PON1仅在中枢神经系统中表达具有保护作用。我们的研究结果支持PON1在缺氧-再氧化损伤中具有保护作用的假设，其在中枢神经系统中的表达足以提供100%的生存保护。
Paraoxonase 1 (PON1) is a protein found associated with high density lipoprotein (HDL), thought to prevent oxidative modification of low-density lipoprotein (LDL). This enzyme has been implicated in lowering the risk of cardiovascular disease. Anoxia-reoxygenation and oxidative stress are important elements in cardiovascular and cerebrovascular disease. However, the role of PON1 in anoxia-reoxygenation or anoxic injury is unclear. We hypothesize that PON1 prevents anoxia-reoxygenation injury. We set out to determine whether PON1 expression in Drosophila melanogaster protects against anoxia-reoxygenation (A-R) induced injury. Wild type (WT) and transgenic PON1 flies were exposed to anoxia (100% Nitrogen) for different time intervals (from 1 to 24 hours). After the anoxic period, flies were placed in room air for reoxygenation. Activity and survival of flies was then recorded. Within 5 minutes of anoxia, all flies fell into a stupor state. After reoxygenation, survivor flies resumed activity with some delay. Interestingly, transgenic flies recovered from stupor later than WT. PON1 transgenic flies had a significant survival advantage after A-R stress compared with WT. The protection conferred by PON1 expression was present regardless of the age or dietary restriction. Furthermore, PON1 expression exclusively in CNS conferred protection. Our results support the hypothesis that PON1 has a protective role in anoxia-reoxygenation injury, and its expression in the CNS is sufficient and necessary to provide a 100% survival protection.
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DOI：
10.1097/gim.0b013e3181ee81c6
发表时间：
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期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
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