Distinct mechanisms underlying tolerance to intermittent and constant hypoxia in Drosophila melanogaster.
Distinct mechanisms underlying tolerance to intermittent and constant hypoxia in Drosophila melanogaster.
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DOI：
10.1371/journal.pone.0005371
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Haddad GG
中科院分区：
文献类型：
--
作者：
Azad P;Zhou D;Russo E;Haddad GG
持续性缺氧（CH）和间歇性缺氧（IH）发生在几种病理条件下，如哮喘和阻塞性睡眠呼吸暂停。我们的研究重点是以果蝇为模型系统，了解导致缺氧应激损伤或适应的分子机制。我们目前的全基因组研究旨在研究基因表达的变化，并确定保护机制（S）在D。黑腹动物暴露于严重（1%O2）间歇性或持续缺氧后。我们的微阵列分析已经确定了多个基因家族的上调或下调，以应对急性CH或IH。我们观察到基因表达对IH和CH的不同反应，其基因数量和基因家族类型不同。然后，我们研究了候选基因（上调或下调）在严重CH或IH下较长时间（CH-7天，IH-10天）的缺氧耐受性（成人生存）中的作用。热休克蛋白上调（特别是Hsp 23和Hsp 70）导致CH期间P-元件系的成体存活（与对照相比）显著增加。相反，IH处理期间Mdr 49和I（2）08717基因（P-元件系）的上调提供了超过对照的存活优势。这表明用任一范例处理后增加的转录物水平在对严重缺氧的耐受性中起重要作用。此外，通过在特定组织中过表达Hsp 70，我们发现心脏和大脑中Hsp 70的上调在果蝇对CH的耐受中起关键作用。我们观察到基因表达对IH或CH的反应是特异的和范式依赖的。我们已经鉴定了几个基因Hsp 23、Hsp 70、CG 1600、I（2）08717和Mdr 49在CH或IH的缺氧耐受中起重要作用。这些数据为IH或CH导致细胞损伤和发病或适应和存活的机制提供了进一步的线索。
Constant hypoxia (CH) and intermittent hypoxia (IH) occur during several pathological conditions such as asthma and obstructive sleep apnea. Our research is focused on understanding the molecular mechanisms that lead to injury or adaptation to hypoxic stress using Drosophila as a model system. Our current genome-wide study is designed to investigate gene expression changes and identify protective mechanism(s) in D. melanogaster after exposure to severe (1% O2) intermittent or constant hypoxia. Our microarray analysis has identified multiple gene families that are up- or down-regulated in response to acute CH or IH. We observed distinct responses to IH and CH in gene expression that varied in the number of genes and type of gene families. We then studied the role of candidate genes (up-or down-regulated) in hypoxia tolerance (adult survival) for longer periods (CH-7 days, IH-10 days) under severe CH or IH. Heat shock proteins up-regulation (specifically Hsp23 and Hsp70) led to a significant increase in adult survival (as compared to controls) of P-element lines during CH. In contrast, during IH treatment the up-regulation of Mdr49 and l(2)08717 genes (P-element lines) provided survival advantage over controls. This suggests that the increased transcript levels following treatment with either paradigm play an important role in tolerance to severe hypoxia. Furthermore, by over-expressing Hsp70 in specific tissues, we found that up-regulation of Hsp70 in heart and brain play critical role in tolerance to CH in flies. We observed that the gene expression response to IH or CH is specific and paradigm-dependent. We have identified several genes Hsp23, Hsp70, CG1600, l(2)08717 and Mdr49 that play an important role in hypoxia tolerance whether it is in CH or IH. These data provide further clues about the mechanisms by which IH or CH lead to cell injury and morbidity or adaptation and survival.
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发表时间：
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影响因子：
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