Document Detail

Anthranilate fluorescence marks a calcium-propagated necrotic wave that promotes organismal death in C. elegans.
MedLine Citation:
PMID:  23935448     Owner:  NLM     Status:  MEDLINE    
For cells the passage from life to death can involve a regulated, programmed transition. In contrast to cell death, the mechanisms of systemic collapse underlying organismal death remain poorly understood. Here we present evidence of a cascade of cell death involving the calpain-cathepsin necrosis pathway that can drive organismal death in Caenorhabditis elegans. We report that organismal death is accompanied by a burst of intense blue fluorescence, generated within intestinal cells by the necrotic cell death pathway. Such death fluorescence marks an anterior to posterior wave of intestinal cell death that is accompanied by cytosolic acidosis. This wave is propagated via the innexin INX-16, likely by calcium influx. Notably, inhibition of systemic necrosis can delay stress-induced death. We also identify the source of the blue fluorescence, initially present in intestinal lysosome-related organelles (gut granules), as anthranilic acid glucosyl esters--not, as previously surmised, the damage product lipofuscin. Anthranilic acid is derived from tryptophan by action of the kynurenine pathway. These findings reveal a central mechanism of organismal death in C. elegans that is related to necrotic propagation in mammals--e.g., in excitotoxicity and ischemia-induced neurodegeneration. Endogenous anthranilate fluorescence renders visible the spatio-temporal dynamics of C. elegans organismal death.
Cassandra Coburn; Erik Allman; Parag Mahanti; Alexandre Benedetto; Filipe Cabreiro; Zachary Pincus; Filip Matthijssens; Caroline Araiz; Abraham Mandel; Manolis Vlachos; Sally-Anne Edwards; Grahame Fischer; Alexander Davidson; Rosina E Pryor; Ailsa Stevens; Frank J Slack; Nektarios Tavernarakis; Bart P Braeckman; Frank C Schroeder; Keith Nehrke; David Gems
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2013-07-23
Journal Detail:
Title:  PLoS biology     Volume:  11     ISSN:  1545-7885     ISO Abbreviation:  PLoS Biol.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-08-12     Completed Date:  2014-02-11     Revised Date:  2014-04-28    
Medline Journal Info:
Nlm Unique ID:  101183755     Medline TA:  PLoS Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e1001613     Citation Subset:  IM    
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MeSH Terms
Caenorhabditis elegans / chemistry*
Esters / chemistry
Oxidative Stress
ortho-Aminobenzoates / chemistry*
Grant Support
098565//Wellcome Trust; 098565/Z/12/Z//Wellcome Trust; AG033839/AG/NIA NIH HHS; GM088290/GM/NIGMS NIH HHS; R01 AG033921/AG/NIA NIH HHS; R01 GM088290/GM/NIGMS NIH HHS; T32 GM068411/GM/NIGMS NIH HHS; T32 GM068411/GM/NIGMS NIH HHS; //Biotechnology and Biological Sciences Research Council
Reg. No./Substance:
0/Esters; 0/ortho-Aminobenzoates; 118-92-3/anthranilic acid

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