A potential biochemical mechanism underlying the influence of sterol deprivation stress on Caenorhabditis elegans longevity

Mi Cheong, Keun Na, Heekyeong Kim, Seul Ki Jeong, Hyoe Jin Joo, David J. Chitwood, Young-Ki Paik

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Abstract

To investigate the biochemical mechanism underlying the effect of sterol deprivation on longevity in Caenorhabditis elegans, we treated parent worms (P0) with 25-azacoprostane (Aza), which inhibits sitosterol-to-cholesterol conversion, and measured mean lifespan (MLS) in F2 worms. At 25 μM (∼EC50), Aza reduced total body sterol by 82.5%, confirming sterol depletion. Aza (25 μM) treatment of wild-type (N2) C. elegans grown in sitosterol (5 μg/ml) reduced MLS by 35%. Similar results were obtained for the stress-related mutants daf-16(mu86) and gas-1(fc21). Unexpectedly, Aza had essentially no effect on MLS in the stress-resistant daf-2(e1370) or mitochondrial complex II mutant mev-1(kn1) strains, indicating that Aza may target both insulin/IGF-1 signaling (IIS) and mitochondrial complex II. Aza increased reactive oxygen species (ROS) levels 2.7-fold in N2 worms, but did not affect ROS production by mev-1(kn1), suggesting a direct link between Aza treatment and mitochondrial ROS production. Moreover, expression of the stress-response transcription factor SKN-1 was decreased in amphid neurons by Aza and that of DAF-28 was increased when DAF-6 was involved, contributing to lifespan reduction.

Original languageEnglish
Pages (from-to)7248-7256
Number of pages9
JournalJournal of Biological Chemistry
Volume286
Issue number9
DOIs
Publication statusPublished - 2011 Mar 4

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Caenorhabditis elegans
Sterols
Reactive Oxygen Species
25-azacoprostane
Insulin-Like Growth Factor I
Neurons
Transcription Factors
Gases
Cholesterol
Insulin

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Cheong, Mi ; Na, Keun ; Kim, Heekyeong ; Jeong, Seul Ki ; Joo, Hyoe Jin ; Chitwood, David J. ; Paik, Young-Ki. / A potential biochemical mechanism underlying the influence of sterol deprivation stress on Caenorhabditis elegans longevity. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 9. pp. 7248-7256.
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A potential biochemical mechanism underlying the influence of sterol deprivation stress on Caenorhabditis elegans longevity. / Cheong, Mi; Na, Keun; Kim, Heekyeong; Jeong, Seul Ki; Joo, Hyoe Jin; Chitwood, David J.; Paik, Young-Ki.

In: Journal of Biological Chemistry, Vol. 286, No. 9, 04.03.2011, p. 7248-7256.

Research output: Contribution to journalArticle

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