A Potential Biochemical Mechanism Underlying the Influence of Sterol Deprivation Stress on Caenorhabditis elegans Longevity
| Autor: | Hyoe-Jin Joo, Mi Cheong Cheong, Heekyeong Kim, Seul Ki Jeong, Young Ki Paik, David J. Chitwood, Keun Na |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Mitochondrial ROS
Aging medicine.medical_treatment Longevity Mutant Biology Biochemistry Animals Genetically Modified chemistry.chemical_compound medicine Animals Caenorhabditis elegans Molecular Biology Transcription factor chemistry.chemical_classification Reactive oxygen species Cholesterol Insulin Cell Biology Lipid Metabolism biology.organism_classification Sitosterols Sterol Mitochondria Cell biology Oxidative Stress chemistry Azasteroids Reactive Oxygen Species Developmental Biology |
| Zdroj: | Journal of Biological Chemistry. 286:7248-7256 |
| ISSN: | 0021-9258 |
| Popis: | 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 (∼EC(50)), 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. |
| Databáze: | OpenAIRE |
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