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Anthranilate fluorescence marks a calcium-propagated necrotic wave that promotes organismal death in C. elegans

(2013) PLOS BIOLOGY. 11(7).
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Abstract
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.
Keywords
PROGRAMMED CELL-DEATH, NEMATODE CAENORHABDITIS-ELEGANS, OXIDATIVE STRESS, IN-VIVO, ENDOPLASMIC-RETICULUM, RHYTHMIC BEHAVIOR, GENETIC-ANALYSIS, NEURONAL DEATH, GAP-JUNCTIONS, LIFE-SPAN

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Chicago
Coburn, Cassandra, Erik Allman, Parag Mahanti, Alexandre Benedetto, Filipe Cabreiro, Zachary Pincus, Filip Matthijssens, et al. 2013. “Anthranilate Fluorescence Marks a Calcium-propagated Necrotic Wave That Promotes Organismal Death in C. Elegans.” Plos Biology 11 (7).
APA
Coburn, C., Allman, E., Mahanti, P., Benedetto, A., Cabreiro, F., Pincus, Z., Matthijssens, F., et al. (2013). Anthranilate fluorescence marks a calcium-propagated necrotic wave that promotes organismal death in C. elegans. PLOS BIOLOGY, 11(7).
Vancouver
1.
Coburn C, Allman E, Mahanti P, Benedetto A, Cabreiro F, Pincus Z, et al. Anthranilate fluorescence marks a calcium-propagated necrotic wave that promotes organismal death in C. elegans. PLOS BIOLOGY. 2013;11(7).
MLA
Coburn, Cassandra, Erik Allman, Parag Mahanti, et al. “Anthranilate Fluorescence Marks a Calcium-propagated Necrotic Wave That Promotes Organismal Death in C. Elegans.” PLOS BIOLOGY 11.7 (2013): n. pag. Print.
@article{4130154,
  abstract     = {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.},
  articleno    = {e1001613},
  author       = {Coburn, Cassandra and Allman, Erik and Mahanti, Parag and Benedetto, Alexandre and Cabreiro, Filipe and Pincus, Zachary and Matthijssens, Filip and Araiz, Caroline and Mandel, Abraham and Vlachos, Manolis and Edwards, Sally-Anne and Fischer, Grahame and Davidson, Alexander and Pryor, Rosina E and Stevens, Ailsa and Slack, Frank J and Tavernarakis, Nektarios and Braeckman, Bart and Schroeder, Frank C and Nehrke, Keith and Gems, David},
  issn         = {1545-7885},
  journal      = {PLOS BIOLOGY},
  keywords     = {PROGRAMMED CELL-DEATH,NEMATODE CAENORHABDITIS-ELEGANS,OXIDATIVE STRESS,IN-VIVO,ENDOPLASMIC-RETICULUM,RHYTHMIC BEHAVIOR,GENETIC-ANALYSIS,NEURONAL DEATH,GAP-JUNCTIONS,LIFE-SPAN},
  language     = {eng},
  number       = {7},
  pages        = {17},
  title        = {Anthranilate fluorescence marks a calcium-propagated necrotic wave that promotes organismal death in C. elegans},
  url          = {http://dx.doi.org/10.1371/journal.pbio.1001613},
  volume       = {11},
  year         = {2013},
}

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