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The Oxidative Stress Response in Caenorhabditis elegans Requires the GATA Transcription Factor ELT-3 and SKN-1/Nrf2

机译:秀丽隐杆线虫的氧化应激反应需要GATA转录因子ELT-3和SKN-1 / Nrf2

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摘要

Cellular damage caused by reactive oxygen species is believed to be a major contributor to age-associated diseases. Previously, we characterized the Caenorhabditis elegans Brap2 ortholog () and found that it is required to prevent larval arrest in response to elevated levels of oxidative stress. Here, we report that C. elegans mutants display increased expression of -dependent, phase II detoxification enzymes that is dependent on (a p38 MAPK C. elegans ortholog). An RNA-interference screen was conducted using a transcription factor library to identify genes required for increased expression of the target in mutants. We identified , a member of the GATA transcription factor family, as a positive regulator of gst-4p::gfp expression. We found that interacts with to activate transcription in vitro and that is required for enhanced expression in the () mutant in vivo. Furthermore, nematodes overexpressing required href="http://www.wormbase.org/db/get?name=WBGene00001251;class=Gene" data-ga-action="click_feat_suppl" ref="reftype=extlink&article-id=5560797&issue-id=297120&journal-id=301&FROM=Article%7CFront%20Matter&TO=External%7CLink%7CURI" target="_blank">ELT-3 for life-span extension. Taken together, these results suggest a model where href="http://www.wormbase.org/db/get?name=WBGene00017144;class=Gene" data-ga-action="click_feat_suppl" ref="reftype=extlink&article-id=5560797&issue-id=297120&journal-id=301&FROM=Article%7CFront%20Matter&TO=External%7CLink%7CURI" target="_blank">BRAP-2 acts as negative regulator of href="http://www.wormbase.org/db/get?name=WBGene00004804;class=Gene" data-ga-action="click_feat_suppl" ref="reftype=extlink&article-id=5560797&issue-id=297120&journal-id=301&FROM=Article%7CFront%20Matter&TO=External%7CLink%7CURI" target="_blank">SKN-1 through inhibition of p38 MAPK activity, and that the GATA transcription factor href="http://www.wormbase.org/db/get?name=WBGene00001251;class=Gene" data-ga-action="click_feat_suppl" ref="reftype=extlink&article-id=5560797&issue-id=297120&journal-id=301&FROM=Article%7CFront%20Matter&TO=External%7CLink%7CURI" target="_blank">ELT-3 is required along with href="http://www.wormbase.org/db/get?name=WBGene00004804;class=Gene" data-ga-action="click_feat_suppl" ref="reftype=extlink&article-id=5560797&issue-id=297120&journal-id=301&FROM=Article%7CFront%20Matter&TO=External%7CLink%7CURI" target="_blank">SKN-1 for the phase II detoxification response in C. elegans.
机译:由活性氧引起的细胞损伤被认为是与年龄有关的疾病的主要诱因。以前,我们对秀丽隐杆线虫Brap2 ortholog()进行了表征,发现需要防止幼虫因氧化应激水平升高而停滞。在这里,我们报告秀丽隐杆线虫突变体显示依赖(p38 MAPK秀丽隐杆线虫直系同源物)依赖的,II期解毒酶的表达增加。使用转录因子文库进行RNA干扰筛选,以鉴定突变体中靶标表达增加所需的基因。我们确定GATA转录因子家族的成员是gst-4p :: gfp表达的正向调节剂。我们发现与相互作用可在体外激活转录,这是在()体内突变体中增强表达所必需的。此外,线虫过表达所需的href =“ http://www.wormbase.org/db/get?name=WBGene00001251;class=Gene” data-ga-action =“ click_feat_suppl” ref =“ reftype = extlink&article-id = 5560797&issue-id = 297120&journal-id = 301&FROM = Article%7CFront%20Matter&TO = External%7CLink%7CURI“ target =” _ blank“> ELT-3 以延长使用寿命。总而言之,这些结果提出了一个模型,其中href =“ http://www.wormbase.org/db/get?name=WBGene00017144;class=Gene” data-ga-action =“ click_feat_suppl” ref =“ reftype = extlink&article-id = 5560797&issue-id = 297120&journal-id = 301&FROM = Article%7CFront%20Matter&TO = External%7CLink%7CURI“ target =” _ blank“> BRAP-2 充当href =” http ://www.wormbase.org/db/get?name = WBGene00004804; class = Gene“ data-ga-action =” click_feat_suppl“ ref =” reftype = extlink&article-id = 5560797&issue-id = 297120&journal-id = 301&FROM = Article %7CFront%20Matter&TO = External%7CLink%7CURI“ target =” _ blank“> SKN-1 通过抑制p38 MAPK活性以及GATA转录因子href =” http://www.wormbase。 org / db / get?name = WBGene00001251; class = Gene“ data-ga-action =” click_feat_suppl“ ref =” reftype = extlink&article-id = 5560797&issue-id = 297120&journal-id = 301&FROM = Article%7CFront%20Matter&TO = External% 7CLink%7CURI“ target =” _ blank“> ELT-3 和href =” http://www.wormbase.org/db/g et?name = WBGene00004804; class = Gene“ data-ga-action =” click_feat_suppl“ ref =” reftype = extlink&article-id = 5560797&issue-id = 297120&journal-id = 301&FROM = Article%7CFront%20Matter&TO = External%7CLink%7CURI“ target =“ _ blank”> SKN-1 用于秀丽隐杆线虫的II期解毒反应。

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