RRC ID 46033
Author Labuschagne CF, Stigter EC, Hendriks MM, Berger R, Rokach J, Korswagen HC, Brenkman AB.
Title Quantification of in vivo oxidative damage in Caenorhabditis elegans during aging by endogenous F3-isoprostane measurement.
Journal Aging Cell
Abstract Oxidative damage is thought to be a major cause in development of pathologies and aging. However, quantification of oxidative damage is methodologically difficult. Here, we present a robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach for accurate, sensitive, and linear in vivo quantification of endogenous oxidative damage in the nematode Caenorhabditis elegans, based on F3-isoprostanes. F3-isoprostanes are prostaglandin-like markers of oxidative damage derived from lipid peroxidation by Reactive Oxygen Species (ROS). Oxidative damage was quantified in whole animals and in multiple cellular compartments, including mitochondria and peroxisomes. Mutants of the mitochondrial electron transport proteins mev-1 and clk-1 showed increased oxidative damage levels. Furthermore, analysis of Superoxide Dismutase (sod) and Catalase (ctl) mutants uncovered that oxidative damage levels cannot be inferred from the phenotype of resistance to pro-oxidants alone and revealed high oxidative damage in a small group of chemosensory neurons. Longitudinal analysis of aging nematodes revealed that oxidative damage increased specifically with postreproductive age. Remarkably, aging of the stress-resistant and long-lived daf-2 insulin/IGF-1 receptor mutant involved distinct daf-16-dependent phases of oxidative damage including a temporal increase at young adulthood. These observations are consistent with a hormetic response to ROS.
Volume 12(2)
Pages 214-23
Published 2013-4-1
DOI 10.1111/acel.12043
PMID 23279719
MeSH Aging / genetics Aging / metabolism* Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Catalase / genetics Catalase / metabolism Cytochromes b Forkhead Transcription Factors Gene Expression Insulin / genetics Insulin / metabolism Isoprostanes / analysis Isoprostanes / metabolism* Mitochondria / metabolism* Mutation Oxidation-Reduction Peroxisomes / metabolism* Reactive Oxygen Species / metabolism Receptor, IGF Type 1 / genetics Receptor, IGF Type 1 / metabolism Receptor, Insulin / genetics Receptor, Insulin / metabolism Sensory Receptor Cells Succinate Dehydrogenase / genetics Succinate Dehydrogenase / metabolism Superoxide Dismutase / genetics Superoxide Dismutase / metabolism Transcription Factors / genetics Transcription Factors / metabolism
IF 7.238
Times Cited 27
C.elegans tm760 tm776 tm1146