The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans
The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans
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DOI：
10.1096/fasebj.13.11.1385
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发表时间：
1999-08-01
期刊：
影响因子：
4.8
通讯作者：
Honda, S
中科院分区：
文献类型：
--
作者：
Honda, Y;Honda, S
在秀丽线虫中，寿命是由daf-2基因网络调节的，daf-2基因的突变赋予了寿命延长(Age)表型和构成的dauer(一种专门用于分散的生长停滞的幼虫形式)形成表型，daf-2基因和clk-1基因的两个寿命延长突变相互增强了age表型，clk-1基因是酵母CAT5/COQ7的同源基因，已知其调节泛醌的生物合成。本研究证明，daf-2突变还赋予了氧化应激抵抗(Oxr)表型，该表型也被CLK-1突变所增强与Age表型类似，Oxr表型受胰岛素样信号通路的调控，从daf-2到daf-16基因，这是HNF-3/Forkhead转录因子的同源物，这些发现使我们研究胰岛素样信号通路是否调节抗氧化防御酶的基因表达。我们发现，编码锰超氧化物歧化酶的sod-3基因在daf-2突变体中的mRNA水平远高于野生型。此外，SOD-3基因表达增加的表型受胰岛素样信号通路的调节。虽然clk-1突变体本身没有表现出oxr和sod-3表达增加的表型，但clk-1突变增强了daf-2突变体的这些表型，这表明clk-1通过两种方式参与长寿：clk-1组成原始的clk-1长寿程序和daf-2长寿程序。这些观察表明，daf-2基因网络通过调节与MnSOD相关的抗氧化防御系统来控制寿命，该系统似乎在Dauer阶段的有效生命维持中发挥作用。
Longevity is regulated by the daf-2 gene network in Caenorhabditis elegans, Mutations in the daf-2 gene, which encodes a member of the insulin receptor family, confer the life extension (Age) phenotype and the constitutive dauer (a growth-arrested larval form specialized for dispersal) formation phenotype, The Age phenotype is mutually potentiated by two life extension mutations in the daf-2 gene and the clk-1 gene, a homologue of yeast CAT5/COQ7 known to regulate ubiquinone biosynthesis, Zn this study, we demonstrated that the daf-2 mutation also conferred an oxidative stress resistance (Oxr) phenotype, which was also enhanced by the clk-1 mutation, Similar to the Age phenotype, the Oxr phenotype was regulated by the genetic pathway of insulin-like signaling from daf-2 to the daf-16 gene, a homologue of the HNF-3/forkhead transcription factor, These findings led us to examine whether the insulin-like signaling pathway regulates the gene expression of antioxidant defense enzymes. We found that the mRNA level of the sod-3 gene, which encodes Mn-superoxide dismutase (SOD), was much higher in daf-2 mutants than in the wild type. Moreover, the increased sod-3 gene expression phenotype is regulated by the insulin-like signaling pathway. Although the clk-1 mutant itself did not display Oxr and the increased sod-3 expression phenotypes, the clk-1 mutation enhanced them in the daf-2 mutant, suggesting that clk-1 is involved in longevity in two ways: clk-1 composes the original clk-1 longevity program and the daf-2 longevity program. These observations suggest that the daf-2 gene network controls longevity by regulating the MnSOD-associated antioxidant defense system, This system appears to play a role in efficient life maintenance at the dauer stage.