Girardot Fabrice, Monnier Véronique, Tricoire Hervé
Institut Jacques Monod, 2 place Jussieu, 75251 Paris, France.
BMC Genomics. 2004 Sep 30;5:74. doi: 10.1186/1471-2164-5-74.
During their life, multicellular organisms are challenged with oxidative stress. It is generated by several reactive oxygen species (ROS), may limit lifespan and has been related to several human diseases. ROS can generate a wide variety of defects in many cellular components and thus the response of the organism challenged with oxidative stress may share some features with other stress responses. Conversely, in spite of recent progress, a complete functional analysis of the transcriptional responses to different oxidative stresses in model organisms is still missing. In addition, the functional significance of observed transcriptional changes is still elusive.
We used oligonucleotide microarrays to address the specificities of transcriptional responses of adult Drosophila to different stresses induced by paraquat and H2O2, two oxidative stressors, and by tunicamycin which induces an endoplasmic reticulum (ER) stress. Both specific and common responses to the three stressors were observed and whole genome functional analysis identified several important classes of stress responsive genes. Within some functional classes, we observed that isozymes do not all behave similarly, which may reflect unsuspected functional specificities. Moreover, genetic experiments performed on a subset of lines bearing mutations in genes identified in microarray experiments showed that a significant number of these mutations may affect resistance of adult Drosophila to oxidative stress.
A long term common stress response to paraquat- or H2O2-induced oxidative stresses and ER stress is observed for a significant number of genes. Besides this common response, the unexpected complexity of the stress responses to oxidative and ER stresses in Drosophila, suggest significant specificities in protective properties between genes associated to the same functional classes. According to our functional analysis, a large part of the genome may play a role in protective mechanisms against oxidative stress in Drosophila.
在其生命过程中，多细胞生物面临氧化应激的挑战。氧化应激由多种活性氧（ROS）产生，可能会限制寿命，并与多种人类疾病相关。ROS可在许多细胞成分中产生各种各样的缺陷，因此受到氧化应激挑战的生物体的反应可能与其他应激反应有一些共同特征。相反，尽管最近取得了进展，但对模式生物中不同氧化应激的转录反应进行完整的功能分析仍然缺失。此外，观察到的转录变化的功能意义仍然难以捉摸。
我们使用寡核苷酸微阵列来研究成年果蝇对百草枯和过氧化氢这两种氧化应激源以及衣霉素（它会诱导内质网应激）所诱导的不同应激的转录反应特异性。观察到了对这三种应激源的特异性和共同反应，全基因组功能分析确定了几类重要的应激反应基因。在一些功能类别中，我们观察到同工酶的表现并不都相似，这可能反映了未被怀疑的功能特异性。此外，对微阵列实验中鉴定出的基因发生突变的部分品系进行的遗传实验表明，这些突变中有相当一部分可能会影响成年果蝇对氧化应激的抗性。
对于大量基因，观察到对百草枯或过氧化氢诱导的氧化应激和内质网应激存在长期的共同应激反应。除了这种共同反应外，果蝇对氧化应激和内质网应激的应激反应出人意料的复杂性表明，同一功能类别的相关基因在保护特性方面存在显著的特异性。根据我们的功能分析，基因组的很大一部分可能在果蝇对抗氧化应激的保护机制中发挥作用。
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