Transcriptional, proteomic, and metabolic responses to lithium in galactose-grown yeast cells
Transcriptional, proteomic, and metabolic responses to lithium in galactose-grown yeast cells
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DOI：
10.1074/jbc.m304478200
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发表时间：
2003-08-22
影响因子：
4.8
通讯作者：
Nielsen, J
中科院分区：
文献类型：
--
作者：
Bro, C;Regenberg, B;Nielsen, J
锂对半乳糖培养基中生长的酵母菌有很高的毒性，主要是因为半乳糖代谢的关键酶磷酸葡萄糖变位酶受到抑制。我们研究了在半乳糖中生长的酿酒酵母在添加锂后的不同时间间隔内的全局蛋白质和基因表达谱。这些结果与测定分泌和细胞内代谢物的生理学研究有关。微阵列分析显示，664个开放阅读框下调，725个上调，以响应锂的添加。参与转录、翻译和核苷酸代谢的基因在转录水平下调，而响应不同胁迫的基因以及能量储备代谢和单糖代谢的基因在转录水平上调。与蛋白质组数据相比，26%的下调和48%的上调蛋白也被确定为在mRNA水平上发生了变化。从蛋白质组数据中获得的功能簇与转录簇一致。生理研究表明，乙酸，甘油和糖原积累响应锂，反映在表达数据，而从呼吸发酵呼吸生长的变化不能预测的表达分析。
Lithium is highly toxic to yeast when grown in galactose medium mainly because phosphoglucomutase, a key enzyme of galactose metabolism, is inhibited. We studied the global protein and gene expression profiles of Saccharomyces cerevisiae grown in galactose in different time intervals after addition of lithium. These results were related to physiological studies where both secreted and intracellular metabolites were determined. Microarray analysis showed that 664 open reading frames were down-regulated and 725 up-regulated in response to addition of lithium. Genes involved in transcription, translation, and nucleotide metabolism were down-regulated at the transcriptional level, whereas genes responsive to different stresses as well as genes from energy reserve metabolism and monosaccharide metabolism were up-regulated. Compared with the proteomic data, 26% of the down-regulated and 48% of the up-regulated proteins were also identified as being changed on the mRNA level. Functional clusters obtained from proteome data were coincident with transcriptional clusters. Physiological studies showed that acetate, glycerol, and glycogen accumulate in response to lithium, as reflected in expression data, whereas a change from respiro-fermentative to respiratory growth could not be predicted from the expression analyses.