Involvement of yeast sphingolipids in the heat stress response of Saccharomyces cerevisiae

Involvement of yeast sphingolipids in the heat stress response of Saccharomyces cerevisiae
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DOI:
10.1074/jbc.272.51.32566
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发表时间:
1997-12-19
影响因子:
4.8
通讯作者:
Hannun, Y
Hannun, Y
中科院分区:
生物学2区
文献类型:
--
作者:
Jenkins, GM;Richards, A;Hannun, Y

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鞘脂在酵母热应激反应中的作用已经通过分离缺乏这些脂质的突变体的抑制因子提出,这些突变体不能在高温下生长。目前的研究考察鞘脂在酵母细胞热适应中的可能作用,通过生长和活力研究监测。长链碱基营养不良抑制因子(SLC,菌株7R4)表现出热敏表型,并通过丝氨酸棕榈酰转移酶转化加以纠正。由此可见,引起SLC菌株7R4热敏表型的原因是鞘脂缺乏,而不是抑制基因突变。鞘脂对热敏表型的修复能力进行了研究,发现两种内源性酵母鞘脂主干植物鞘脂和二氢鞘脂在这一作用中最有效。接下来,研究人员确定了热应激对三种主要鞘脂类水平的影响。在1.5 h的时间过程中,肌醇磷酸神经酰胺没有变化,但在15 min的热应激后,四种检测到的鞘碱从1.4倍增加到10.8倍。增幅最大的是两种鞘碱,C-20植物鞘苷和C-20二氢鞘苷,分别比基线增加了6.4倍和10.8倍。在热应激60分钟时,两种酵母神经酰胺比基线增加了9.2倍和10.6倍。神经酰胺合成酶抑制剂伏马菌素B1部分降低了神经酰胺的增加。因此,热应激诱导鞘鞘碱和神经酰胺的积累,可能是通过从头合成的方式。综上所述,这些结果表明鞘脂参与了酵母的热应激适应。
A role for sphingolipids in the yeast heat stress response has been suggested by the isolation of suppressors of mutants lacking these lipids, which are unable to grow at elevated temperatures. The current study examines the possible role of sphingolipids in the heat adaptation of yeast cells as monitored by growth and viability studies. The suppressor of long chain base auxotrophy (SLC, strain 7R4) showed a heat-sensitive phenotype that was corrected by transformation with serine palmitoyltransferase. Thus, the deficiency in sphingolipids and not the suppressor mutation was the cause of the heat-sensitive phenotype of the SLC strain 7R4. The ability of sphingolipids to rescue the heat-sensitive phenotype was examined, and two endogenous yeast sphingoid backbones, phytosphingosine and dihydrosphingosine, were found to be most potent in this effect. Next, the effect of heat stress on the levels of the three major classes of sphingolipids was determined. The inositol phosphoceramides showed no change over a 1.5-h time course, However, the four detected species of sphingoid bases increased after 15 min of heat stress from 1.4- to 10.8-fold. The largest increases were seen in two sphingoid bases, C-20 phytosphingosine and C-20 dihydrosphingosine, which increased 6.4- and 10.8-fold over baseline, respectively. At 60 min of heat stress two species of yeast ceramide increased by 9.2- and 10.6-fold over baseline. The increase seen in the ceramides was partially decreased by Fumonisin B1, a ceramide synthase inhibitor. Therefore, heat stress induces accumulation of sphingoid bases and of ceramides, probably through de novo synthesis, Taken together, these results demonstrate that sphingolipids are involved in the yeast heat stress adaptation.