| Citation | Mabon ME, Scott BA, Crowder CM. Divergent mechanisms controlling hypoxic sensitivity and lifespan by the DAF-2/insulin/IGF-receptor pathway. PLoS One, 2009. |
| PubMed ID | 19936206 |
| Short Description | Divergent mechanisms controlling hypoxic sensitivity and lifespan by the DAF-2/insulin/IGF-receptor pathway. GEO Record: GSE18601 Platform: GPL9458 Download gene-centric, log2 transformed data: WBPaper00035504.ce.mr.csv |
| # of Conditions | 18 |
Full Description
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Organisms and their cells vary greatly in their tolerance of low oxygen environments (hypoxia). A delineation of the determinants of hypoxia tolerance is incomplete, despite intense interest for its implications in diseases such as stroke and myocardial infarction. The insulin/IGF-1 receptor (IGFR) signaling pathway controls survival of Caenorhabditis elegans from a variety of stressors including aging, hyperthermia, and hypoxia. daf-2 encodes a C. elegans IGFR homolog whose primary signaling pathway modulates the activity of the FOXO transcription factor DAF-16. DAF-16 regulates the transcription of a large number of genes, some of which have been shown to control aging. To identify genes that selectively regulate hypoxic sensitivity, we compared the whole-organismal transcriptomes of three daf-2 reduction-of-function alleles, all of which are hypoxia resistant, thermotolerant, and long lived, but differ in their rank of severities for these phenotypes. The transcript levels of 172 genes were increased in the most hypoxia resistant daf-2 allele, e1370, relative to the other alleles whereas transcripts from only 10 genes were decreased in abundance. RNAi knockdown of 6 of the 10 genes produced a significant increase in organismal survival after hypoxic exposure as would be expected if down regulation of these genes by the e1370 mutation was responsible for hypoxia resistance. However, RNAi knockdown of these genes did not prolong lifespan. These genes definitively separate the mechanisms of hypoxic sensitivity and lifespan and identify biological strategies to survive hypoxic injury. Experimental Details: WBPaper00035504:m596_1 WBPaper00035504:m596_2 WBPaper00035504:m596_3 WBPaper00035504:e1368_1 WBPaper00035504:e1368_2 WBPaper00035504:e1368_3 WBPaper00035504:m596_4 WBPaper00035504:m596_5 WBPaper00035504:m596_6 WBPaper00035504:e1370_1 WBPaper00035504:e1370_2 WBPaper00035504:e1370_3 WBPaper00035504:e1370_4 WBPaper00035504:e1370_5 WBPaper00035504:e1370_6 WBPaper00035504:e1368_4 WBPaper00035504:e1368_5 WBPaper00035504:e1368_6. |
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