PMID- 25971936 OWN - NLM STAT- MEDLINE DCOM- 20160510 LR - 20181113 IS - 2160-1836 (Electronic) IS - 2160-1836 (Linking) VI - 5 IP - 7 DP - 2015 May 12 TI - No Significant Increase in the Delta4- and Delta7-Dafachronic Acid Concentration in the Long-Lived glp-1 Mutant, nor in the Mutants Defective in Dauer Formation. PG - 1473-9 LID - 10.1534/g3.115.018812 [doi] AB - The steroid hormone dafachronic acid (DA) regulates dauer formation and lifespan in Caenorhabditis elegans by binding to the nuclear receptor DAF-12. However, little is known about how DA concentrations change under various physiologic conditions and about how DA/DAF-12 signaling interacts with other signaling pathways that also regulate dauer formation and lifespan. Using a sensitive bioanalytical method, we quantified the endogenous DA concentrations in a long-lived germline-less glp-1 mutant and in the Dauer formation-defective (Daf-d) mutants daf-12, daf-16, daf-5, and daf-3. We found that the DA concentration in the glp-1 mutant was similar to that in the wild type (WT). This result is contrary to the long-held belief that germline loss-induced longevity involves increased DA production and suggests instead that this type of longevity involves an enhanced response to DA. We also found evidence suggesting that increased DA sensitivity underlies lifespan extension triggered by exogenous DA. At the L2/L3 stage, the DA concentration in a daf-12 null mutant decreased to 22% of the WT level. This finding is consistent with the previously proposed positive feedback regulation between DAF-12 and DA production. Surprisingly, the DA concentrations in the daf-16, daf-5, and daf-3 mutants were only 19-34% of the WT level at the L2/L3 stage, slightly greater than those in the Dauer formation-constitutive (Daf-c) mutants at the pre-dauer stage (4-15% of the WT L2 control). Our experimental evidence suggested that the positive feedback between DA and DAF-12 was partially induced in the three Daf-d mutants. CI - Copyright (c) 2015 Li et al. FAU - Li, Tie-Mei AU - Li TM AD - National Institute of Biological Sciences, Beijing, Beijing 102206, China. FAU - Liu, Weilong AU - Liu W AD - National Institute of Biological Sciences, Beijing, Beijing 102206, China. FAU - Lu, Shan AU - Lu S AD - National Institute of Biological Sciences, Beijing, Beijing 102206, China. FAU - Zhang, Yan-Ping AU - Zhang YP AD - National Institute of Biological Sciences, Beijing, Beijing 102206, China. FAU - Jia, Le-Mei AU - Jia LM AD - National Institute of Biological Sciences, Beijing, Beijing 102206, China. FAU - Chen, Jie AU - Chen J AD - National Institute of Biological Sciences, Beijing, Beijing 102206, China. FAU - Li, Xiangke AU - Li X AD - National Institute of Biological Sciences, Beijing, Beijing 102206, China. FAU - Lei, Xiaoguang AU - Lei X AD - National Institute of Biological Sciences, Beijing, Beijing 102206, China Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center, and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. FAU - Dong, Meng-Qiu AU - Dong MQ AUID- ORCID: 0000-0002-6094-1182 AD - National Institute of Biological Sciences, Beijing, Beijing 102206, China dongmengqiu@nibs.ac.cn. LA - eng GR - P40 OD010440/OD/NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20150512 PL - England TA - G3 (Bethesda) JT - G3 (Bethesda, Md.) JID - 101566598 RN - 0 (Caenorhabditis elegans Proteins) RN - 0 (Cholestenes) RN - 0 (Glp-1 protein, C elegans) RN - 0 (Receptors, Notch) RN - 0 (delta4-dafachronic acid) RN - 0 (delta7-dafachronic acid) SB - IM MH - Animals MH - Animals, Genetically Modified/genetics/metabolism MH - Caenorhabditis elegans/genetics/growth & development/*metabolism MH - Caenorhabditis elegans Proteins/*genetics/metabolism MH - Cholestenes/*analysis MH - Chromatography, High Pressure Liquid MH - Germ Cells/metabolism MH - Larva/metabolism MH - Longevity MH - Mass Spectrometry MH - Mutation MH - Real-Time Polymerase Chain Reaction MH - Receptors, Notch/*genetics/metabolism MH - Signal Transduction MH - Temperature PMC - PMC4502381 OTO - NOTNLM OT - C. elegans dauer OT - daf-12 OT - dafachronic acid OT - glp-1 OT - steroid hormone EDAT- 2015/05/15 06:00 MHDA- 2016/05/11 06:00 PMCR- 2015/05/12 CRDT- 2015/05/15 06:00 PHST- 2015/05/15 06:00 [entrez] PHST- 2015/05/15 06:00 [pubmed] PHST- 2016/05/11 06:00 [medline] PHST- 2015/05/12 00:00 [pmc-release] AID - g3.115.018812 [pii] AID - GGG_018812 [pii] AID - 10.1534/g3.115.018812 [doi] PST - epublish SO - G3 (Bethesda). 2015 May 12;5(7):1473-9. doi: 10.1534/g3.115.018812.