Show simple item record

dc.contributor.author
Urban, Nadine
dc.contributor.author
Tsitsipatis, Dimitrios
dc.contributor.author
Hausig, Franziska
dc.contributor.author
Kreuzer, Katrin
dc.contributor.author
Erler, Katrin
dc.contributor.author
Stein, Vanessa
dc.contributor.author
Ristow, Michael
dc.contributor.author
Steinbrenner, Holger
dc.contributor.author
Klotz, Lars-Oliver
dc.date.accessioned
2018-02-19T11:20:02Z
dc.date.available
2018-01-15T17:25:00Z
dc.date.available
2018-02-19T11:17:52Z
dc.date.available
2017-06-12T19:38:30Z
dc.date.available
2018-02-19T11:20:02Z
dc.date.issued
2017-04
dc.identifier.other
10.1016/j.redox.2016.12.003
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/242322
dc.identifier.doi
10.3929/ethz-b-000242322
dc.description.abstract
The redox environment in cells and organisms is set by low-molecular mass and protein-bound thiols, with glutathione (GSH) representing a major intracellular redox buffer. Subtle thiol oxidation elicits signal transduction processes and adaptive responses to cope with stressors, whereas highly oxidizing conditions may provoke cell death. We here tested how thiol depletion affects life span, stress resistance and stress signaling in the model organism Caenorhabditis elegans. Diethyl maleate (DEM), an α,β-unsaturated carbonyl compound that conjugates to GSH and other thiols, decreased C. elegans life span at a concentration of 1 mM. In contrast, low and moderate doses of DEM (10–100 µM) increased mean and maximum life span and improved resistance against oxidative stress. DEM-induced life span extension was not detectable in worms deficient in either the FoxO orthologue, DAF-16, or the Nrf2 orthologue, SKN-1, pointing to a collaborative role of the two transcription factors in life span extension induced by thiol depletion. Cytoprotective target genes of DAF-16 and SKN-1 were upregulated after at least 3 days of exposure to 100 µM DEM, but not 1 mM DEM, whereas only 1 mM DEM caused upregulation of egl-1, a gene controlled by a p53-orthologue, CEP-1. In order to test whether depletion of GSH may elicit effects similar to DEM, we suppressed GSH biosynthesis in worms by attenuating γ-glutamylcysteine synthetase (gcs-1) expression through RNAi. The decline in GSH levels elicited by gcs-1 knockdown starting at young adult stage did not impair viability, but increased both stress resistance and life expectancy of the worms. In contrast, gcs-1 knockdown commencing right after hatching impaired nematode stress resistance and rendered young adult worms prone to vulval ruptures during egg-laying. Thus, modest decrease in GSH levels in young adult worms may promote stress resistance and life span, whereas depletion of GSH is detrimental to freshly hatched and developing worms.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Elsevier
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Glutathione
en_US
dc.subject
C. elegans
en_US
dc.subject
Aging
en_US
dc.subject
Stress resistance
en_US
dc.subject
Thiol
en_US
dc.subject
γ-glutamylcysteine synthetase
en_US
dc.subject
Hormesis
en_US
dc.title
Non-linear impact of glutathione depletion on C. elegans life span and stress resistance
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2016-12-06
ethz.journal.title
Redox Biology
ethz.journal.volume
11
en_US
ethz.pages.start
502
en_US
ethz.pages.end
515
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.identifier.nebis
010200839
ethz.publication.place
Amsterdam
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02540 - Institut für Translationale Medizin / Institute of Translational Medicine
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02540 - Institut für Translationale Medizin / Institute of Translational Medicine::03976 - Ristow, Michael / Ristow, Michael
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02540 - Institut für Translationale Medizin / Institute of Translational Medicine::03976 - Ristow, Michael / Ristow, Michael
ethz.date.deposited
2017-06-12T19:38:38Z
ethz.source
BATCH
ethz.source
ECIT
ethz.identifier.importid
imp5936553d6d7a824943
ethz.ecitpid
pub:191155
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2018-02-20T11:35:06Z
ethz.rosetta.lastUpdated
2018-12-02T08:56:55Z
ethz.rosetta.versionExported
true
dc.identifier.olduri
http://hdl.handle.net/20.500.11850/128249
dc.identifier.olduri
http://hdl.handle.net/20.500.11850/229031
ethz.COinS
ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.atitle=Non-linear%20impact%20of%20glutathione%20depletion%20on%20C.%20elegans%20life%20span%20and%20stress%20resistance&rft.jtitle=Redox%20Biology&rft.date=2017-04&rft.volume=11&rft.spage=502&rft.epage=515&rft.au=Urban,%20Nadine&Tsitsipatis,%20Dimitrios&Hausig,%20Franziska&Kreuzer,%20Katrin&Erler,%20Katrin&rft.genre=article&
 Search via SFX

Files in this item

Thumbnail

Publication type

Show simple item record