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题目:: Transcription profiling of S. cerevisiae (budding yeast) mutants reveals Isc1p plays a key role in hydrogen peroxide resistance and chronological lifespan through modulation of iron levels and programmed cell death
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状态:: 发布时间Feb. 5, 2008 , 更新时间 May 2, 2014 , 提交时间 June 6, 2007,
物种:: Saccharomyces cerevisiae
摘要:: Changes in the transcriptome of Isc1p deficient mutants. The inositolphosphosphingolipid phospholipase C (Isc1p) of Saccharomyces cerevisiae belongs to the family of neutral sphingomyelinases that generates the bioactive sphingolipid ceramide. In this work the role of Isc1p in oxidative stress resistance and chronological lifespan was investigated. Loss of Isc1p resulted in a higher sensitivity to hydrogen peroxide that was associated with an increase in oxidative stress markers, namely intracellular oxidation, protein carbonylation and lipid peroxidation. Microarray analysis showed that Isc1p deficiency upregulated the iron regulon leading to increased levels of iron, which is known to catalyze the production of the highly reactive hydroxyl radicals via the Fenton reaction. In agreement, iron chelation suppressed hydrogen peroxide sensitivity of isc1D mutants. Cells lacking Isc1p also displayed a shortened chronological lifespan associated with oxidative stress markers and ageing of parental cells was correlated with a decrease in Isc1p activity. The analysis of DNA fragmentation and caspase activity showed that Isc1p deficiency increased apoptotic programmed cell death associated with oxidative stress and ageing. Furthermore, deletion of Yca1p metacaspase suppressed the oxidative stress sensitivity and premature ageing phenotypes of isc1D mutants. These results indicate that Isc1p plays an important role in the regulation of cellular redox homeostasis, through modulation of iron levels, and of apoptosis.
实验种类:: transcription profiling by array
样本量:: 12
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数据号:: E-MEXP-1136
数据状态:: 无法自动分析，您可以尝试手动分析数据。

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