An explicit test of the phospholipid saturation hypothesis of acquired cold tolerance in Caenorhabditis elegans
An explicit test of the phospholipid saturation hypothesis of acquired cold tolerance in Caenorhabditis elegans
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DOI：
10.1073/pnas.0609590104
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发表时间：
2007-03-27
影响因子：
11.1
通讯作者：
Cossins, Andrew R.
中科院分区：
文献类型：
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作者：
Murray, Patricia;Hayward, Scott A. L.;Cossins, Andrew R.
保护变温动物免受季节性寒冷被广泛认为与膜磷脂不饱和度的变化有因果关系，但在动物中，这一主张尚未得到正式验证。我们现在已经实现了这一点的遗传操作的脂质生物合成的秀丽隐杆线虫独立的温度。从25 ℃转移到10 ℃的蠕虫在几天内发展出对致死冷（0 ℃）的耐受性大大增加，并且磷脂不饱和度也增加，如在高等动物模型中那样。在三个C中。在线虫Delta 9-去饱和酶中，冷转移仅上调了fat-7的转录水平。fat-7的RNAi抑制引起fat-5去饱和酶的诱导，因此为了控制去饱和酶表达，我们将fat-7的RNAi与fat-5敲除组合。这些fat-5/fat-7操纵的蠕虫显示出预期的脂质饱和度和0 ℃下的耐冷性之间的负线性关系，这一结果通过饮食救援证实。然而，这种脂质饱和度的变化仅解释了在25 ℃和10 ℃下保持的动物的耐寒性之间观察到的差异的16%。因此，虽然操纵的脂质饱和度影响可耐受的热窗口，并且改变的Δ 9-去饱和酶表达解释了冷诱导的脂质调节，但是该影响相对较小，并且没有一种脂质操纵足以使蠕虫在完全冷敏感和完全冷耐受状态之间转换。至关重要的是，转移10摄氏度-驯化蠕虫回到25摄氏度导致他们恢复通常的冷敏感表型在24小时内，尽管保留了10摄氏度蠕虫的脂质特征。获得性冷保护的其他非脂质机制明显主导诱导型耐冷性。
Protection of poikilothermic animals from seasonal cold is widely regarded as being causally linked to changes in the unsaturation of membrane phospholipids, yet in animals this proposition remains formally untested. We have now achieved this by the genetic manipulation of lipid biosynthesis of Caenorhabditis elegans independent of temperature. Worms transferred from 25 degrees C to 10 degrees C develop over several days a much-increased tolerance of lethal cold (0 degrees C) and also an increased phospholipid unsaturation, as in higher animal models. Of the three C. elegans Delta 9-desaturases, transcript levels of fat-7 only were up-regulated by cold transfer. RNAi suppression of fat-7 caused the induction of fat-5 desaturase, so to control desaturase expression we combined RNAi of fat-7 with a fat-5 knockout. These fat-5/fat-7 manipulated worms displayed the expected negative linear relationship between lipid saturation and cold tolerance at 0 degrees C, an outcome confirmed by dietary rescue. However, this change in lipid saturation explains just 16% of the observed difference between cold tolerance of animals held at 25 degrees C and 10 degrees C. Thus, although the manipulated lipid saturation affects the tolerable thermal window, and altered Delta 9-desaturase expression accounts for cold-induced lipid adjustments, the effect is relatively small and none of the lipid manipulations were sufficient to convert worms between fully cold-sensitive and fully cold-tolerant states. Critically, transfer of 10 degrees C-acclimated worms back to 25 degrees C led to them restoring the usual cold-sensitive phenotype within 24 h despite retaining a lipid profile characteristic of 10 degrees C worms. Other nonlipid mechanisms of acquired cold protection clearly dominate inducible cold tolerance.