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Anthranilate fluorescence marks a calcium-propagated necrotic wave that promotes organismal death in C. elegans
- Source :
- PLoS Biology; Vol 11, PLOS BIOLOGY, PLoS Biology, PLoS Biology, Vol 11, Iss 7, p e1001613 (2013)
- Publication Year :
- 2013
- Publisher :
- Public Library of Science (PLoS), 2013.
-
Abstract
- Death of the nematode Caenorhabditis elegans involves a conserved necrotic cell death cascade which generates endogenous blue anthranilate fluorescence, allowing death to be visualized.<br />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.<br />Author Summary In the nematode Caenorhabditis elegans, intestinal lysosome-related organelles (or “gut granules”) contain a bright blue fluorescent substance of unknown identity. This has similar spectral properties to lipofuscin, a product of oxidative damage known to accumulate with age in postmitotic mammalian cells. Blue fluorescence seems to increase in aging worm populations, and lipofuscin has been proposed to be the source. To analyze this further, we measure fluorescence levels after exposure to oxidative stress and during aging in individually tracked worms. Surprisingly, neither of these conditions increases fluorescence levels; instead blue fluorescence increases in a striking and rapid burst at death. Such death fluorescence (DF) also appears in young worms when killed, irrespective of age or cause of death. We chemically identify DF as anthranilic acid glucosyl esters derived from tryptophan, and not lipofuscin. In addition, we show that DF generation in the intestine is dependent upon the necrotic cell death cascade, previously characterized as a driver of neurodegeneration. We find that necrosis spreads in a rapid wave along the intestine by calcium influx via innexin ion channels, accompanied by cytosolic acidosis. Inhibition of necrosis pathway components can delay stress-induced death, supporting its role as a driver of organismal death. This necrotic cascade provides a model system to study neurodegeneration and organismal death.
- Subjects :
- Life Sciences & Biomedicine - Other Topics
Kynurenine pathway
Necrosis
Excitotoxicity
medicine.disease_cause
0302 clinical medicine
ortho-Aminobenzoates
Biology (General)
OXIDATIVE STRESS
Caenorhabditis elegans
IN-VIVO
11 Medical and Health Sciences
LIFE-SPAN
NEMATODE CAENORHABDITIS-ELEGANS
0303 health sciences
biology
General Neuroscience
NECROSIS
Neurodegeneration
GAP-JUNCTIONS
Esters
NEURONAL DEATH
3. Good health
Cell biology
ACID
LIPOFUSCIN
medicine.symptom
General Agricultural and Biological Sciences
Life Sciences & Biomedicine
Research Article
Programmed cell death
Biochemistry & Molecular Biology
QH301-705.5
ENDOPLASMIC-RETICULUM
Microbiology
General Biochemistry, Genetics and Molecular Biology
Fluorescence
PROGRAMMED CELL-DEATH
03 medical and health sciences
Model Organisms
GENETIC-ANALYSIS
07 Agricultural and Veterinary Sciences
medicine
Genetics
Animals
Biology
030304 developmental biology
Science & Technology
General Immunology and Microbiology
Biology and Life Sciences
06 Biological Sciences
medicine.disease
biology.organism_classification
Cytosol
Oxidative Stress
CELL-DEATH
Apoptosis
CAENORHABDITIS-ELEGANS
030217 neurology & neurosurgery
RHYTHMIC BEHAVIOR
Developmental Biology
Subjects
Details
- Language :
- English
- ISSN :
- 15457885
- Database :
- OpenAIRE
- Journal :
- PLoS Biology; Vol 11, PLOS BIOLOGY, PLoS Biology, PLoS Biology, Vol 11, Iss 7, p e1001613 (2013)
- Accession number :
- edsair.doi.dedup.....30280814cad0275e96bcf0e473da8743