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蛋白激酶Pka1和Sck2对粟酒裂殖酵母时序衰老的调控

Regulation of chronological aging in Schizosaccharomyces pombe by the protein kinases Pka1 and Sck2.

作者信息

Roux Antoine E, Quissac Aurélie, Chartrand Pascal, Ferbeyre Gerardo, Rokeach Luis A

机构信息

Department of Biochemistry, Université de Montréal, Montréal, Québec, Canada HC3 3J7.

出版信息

Aging Cell. 2006 Aug;5(4):345-57. doi: 10.1111/j.1474-9726.2006.00225.x. Epub 2006 Jul 5.

Abstract

Budding yeast shows a progressive decline in viability after entering stationary phase, a phenomenon known as chronological aging. We show here that the fission yeast Schizosaccharomyces pombe also undergoes chronological aging and that the process is regulated by genes controlling two related nutrient signalling pathways. The first pathway includes the serine/threonine cAMP-activated protein kinase Pka1 and the second pathway comprises the serine/threonine kinase Sck2, a homologue of Saccharomyces cerevisiae SCH9. A double mutant for pka1 and sck2 displayed an additive effect on prolonging the fission yeast lifespan, suggesting that these genes regulate related but independent pathways. These long-lived mutants also accumulated less reactive oxygen species and had a delayed initiation of apoptosis compared with wild-type cells. We also found that strains carrying pka1 deletion but not those with sck2 deletion gained resistance to oxidative stress due to exposure to H(2)O(2) or menadione. On the other hand, the additional increase in lifespan shown by the Deltapka1Deltasck2 double-mutant strain correlated with an increased resistance to both oxidative stress and heat shock. These results underscore the importance of nutrient signalling pathways and reactive oxygen species on organismal lifespan and establish S. pombe as a new model organism to study the molecular mechanisms underlying aging.

摘要

出芽酵母进入稳定期后活力会逐渐下降,这种现象被称为时序衰老。我们在此表明,裂殖酵母粟酒裂殖酵母也会经历时序衰老,且该过程受控制两条相关营养信号通路的基因调节。第一条通路包括丝氨酸/苏氨酸cAMP激活的蛋白激酶Pka1,第二条通路包含丝氨酸/苏氨酸激酶Sck2,它是酿酒酵母SCH9的同源物。pka1和sck2的双突变体在延长裂殖酵母寿命方面表现出累加效应,这表明这些基因调节相关但独立的通路。与野生型细胞相比,这些长寿突变体积累的活性氧也更少,且凋亡起始延迟。我们还发现,携带pka1缺失的菌株,但不包括携带sck2缺失的菌株,由于暴露于H(2)O(2)或甲萘醌而获得了对氧化应激的抗性。另一方面,Deltapka1Deltasck2双突变体菌株显示出的寿命额外延长与对氧化应激和热休克的抗性增加相关。这些结果强调了营养信号通路和活性氧对生物体寿命的重要性,并将粟酒裂殖酵母确立为研究衰老潜在分子机制的新模型生物。

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