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Life without Oxygen: Gene Regulatory Responses of the Crucian Carp (Carassius carassius) Heart Subjected to Chronic Anoxia

机译:没有氧气的生活:慢性缺氧的the鱼(Car鱼)心脏的基因调控反应。

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摘要

Crucian carp are unusual among vertebrates in surviving extended periods in the complete absence of molecular oxygen. During this time cardiac output is maintained though these mechanisms are not well understood. Using a high-density cDNA microarray, we have defined the genome-wide gene expression responses of cardiac tissue after exposing the fish at two temperatures (8 and 13°C) to one and seven days of anoxia, followed by seven days after restoration to normoxia. At 8°C, using a false discovery rate of 5%, neither anoxia nor re-oxygenation elicited appreciable changes in gene expression. By contrast, at 13°C, 777 unique genes responded strongly. Up-regulated genes included those involved in protein turnover, the pentose phosphate pathway and cell morphogenesis while down-regulated gene categories included RNA splicing and transcription. Most genes were affected between one and seven days of anoxia, indicating gene regulation over the medium term but with few early response genes. Re-oxygenation for 7 days was sufficient to completely reverse these responses. Glycolysis displayed more complex responses with anoxia up-regulated transcripts for the key regulatory enzymes, hexokinase and phosphofructokinase, but with down-regulation of most of the non-regulatory genes. This complex pattern of responses in genomic transcription patterns indicates divergent cardiac responses to anoxia, with the transcriptionally driven reprogramming of cardiac function seen at 13°C being largely completed at 8°C.
机译:在完全没有分子氧的情况下存活较长时间的脊椎动物中鱼是不寻常的。在这段时间中,尽管对这些机制还没有很好的理解,但仍维持了心输出量。使用高密度cDNA微阵列,我们确定了鱼在两个温度(8和13°C)下暴露于缺氧1天和7天,然后恢复到7天后心脏组织的全基因组全基因表达响应。常氧在8°C下,使用5%的错误发现率,缺氧或再次充氧都不会引起基因表达的明显变化。相比之下,在13°C时,有777个独特基因反应强烈。上调的基因包括那些涉及蛋白质更新,磷酸戊糖途径和细胞形态发生的基因,而下调的基因类别包括RNA剪接和转录。大多数基因在缺氧的一到七天之间受到影响,这表明中期的基因调控,但早期响应基因很少。再充氧7天足以完全逆转这些反应。糖酵解显示出更复杂的反应,其中关键调节酶己糖激酶和磷酸果糖激酶的缺氧上调转录本,但大多数非调节基因下调。基因组转录模式中这种复杂的反应模式表明心脏对缺氧的反应不同,在13°C时转录驱动的心脏功能重编程在8°C时基本完成。

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