Oxidative stress and longevity in Caenorhabditis elegans as mediated by SKN-1.
Oxidative stress and longevity in Caenorhabditis elegans as mediated by SKN-1.
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DOI：
10.1111/j.1474-9726.2009.00473.x
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发表时间：
2009-06
期刊：
影响因子：
7.8
通讯作者：
Johnson TE
中科院分区：
文献类型：
--
作者：
Park SK;Tedesco PM;Johnson TE
氧化应激已被假设在正常衰老中发挥作用。SKN-1转录因子调节秀丽隐杆线虫对氧化应激的反应，也是肠道发育所必需的。使用转录组分析，我们发现氧化应激诱导近一千个基因，包括抗氧化和热休克反应，以及负责异生物质解毒的基因。还有392个下调的基因，包括许多参与代谢稳态，生物体发育和生殖的基因。许多这些氧化应激诱导的转录变化依赖于SKN-1的行动，热休克反应的诱导不是。当我们使用RNAi来抑制基因时，我们发现大多数基因对氧化应激的抵抗力或寿命没有影响;然而，两个SKN-1依赖性基因nlp-7和cup-4被氧化应激上调，被发现是抵抗氧化应激和正常寿命所必需的。NLP-7编码在神经元中表达的神经肽样蛋白，而Cup-4编码体腔细胞特异性配体门控离子通道。nLP-7或cup-4的RNA干扰增加了对氧化应激的敏感性并缩短了寿命。在下调的基因中，只有抑制ent-1（一种核苷转运蛋白）才能增加对氧化应激的抵抗力;抑制对寿命没有影响。相比之下，nhx-2（Na+/H+交换器）的RNAi显著延长了寿命，而不影响对氧化应激的敏感性。这些发现表明，氧化应激导致从生长和维持到细胞防御机制激活的转录转变;这些转录改变中的许多是SKN-1依赖的。
Oxidative stress has been hypothesized to play a role in normal aging. The SKN-1 transcription factor regulates the response to oxidative stress and also is necessary for intestinal development in Caenorhabditis elegans. Using transcriptome analysis, we found that oxidative stress induces almost a thousand genes, including the antioxidant and heat-shock responses, as well as genes responsible for xenobiotic detoxification. There were also 392 down-regulated genes including many involved in metabolic homeostasis, organismal development, and reproduction. Many of these oxidative-stress-induced transcriptional changes are dependent on SKN-1 action; the induction of the heat-shock response is not. When we used RNAi to inhibit genes, we found that most had no effect on either resistance to oxidative stress or longevity; however two SKN-1-dependent genes, nlp-7 and cup-4, that were up-regulated by oxidative stress were found to be required for resistance to oxidative stress and for normal life span. nlp-7 encodes a neuropeptide-like protein, expressed in neurons, while cup-4 encodes a coelomocyte-specific, ligand-gated ion channel. RNAi of nlp-7 or cup-4 increased sensitivity to oxidative stress and reduced lifespan. Among down-regulated genes, only inhibition of ent-1, a nucleoside transporter, led to increased resistance to oxidative stress; inhibition had no effect on lifespan. In contrast, RNAi of nhx-2, a Na+/H+ exchanger, extended lifespan significantly without affecting sensitivity to oxidative stress. These findings show that oxidative stress causes a transcriptional shift from growth and maintenance towards the activation of cellular defense mechanisms; many of these transcriptional alterations are SKN-1-dependent.
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影响因子：
7.4
作者：
De Castro, E;De Castro, SH;Johnson, TE
通讯作者：
Johnson, TE
影响因子：
64.5
作者：
Budovskaya YV;Wu K;Southworth LK;Jiang M;Tedesco P;Johnson TE;Kim SK
通讯作者：
Kim SK
影响因子：
4.2
作者：
Johnson, TE;Henderson, S;Link, C
通讯作者：
Link, C
DOI：
10.1073/pnas.76.3.1333
发表时间：
1979-01-01
影响因子：
11.1
作者：
EMMONS, SW;KLASS, MR;HIRSH, D
通讯作者：
HIRSH, D
影响因子：
4.8
作者：
Kuzmin, EV;Karpova, OV;Newton, KJ
通讯作者：
Newton, KJ