The metabolic contribution of SKN-1/Nrf2 to the lifespan of Caenorhabditis elegans.

Autor: Phan HD; College of Pharmacy, Natural Products Research Institute, Seoul National University, Sillim-Dong, Gwanak-Gu, Seoul, 08826, South Korea., Nguyen TTM; College of Pharmacy, Natural Products Research Institute, Seoul National University, Sillim-Dong, Gwanak-Gu, Seoul, 08826, South Korea.; Department of Pharmacy, Binh Duong University, Thu Dau Mot, 820000, Vietnam., Lee S; College of Pharmacy, Natural Products Research Institute, Seoul National University, Sillim-Dong, Gwanak-Gu, Seoul, 08826, South Korea., Seo M; College of Pharmacy, Natural Products Research Institute, Seoul National University, Sillim-Dong, Gwanak-Gu, Seoul, 08826, South Korea., An YJ; College of Pharmacy, Natural Products Research Institute, Seoul National University, Sillim-Dong, Gwanak-Gu, Seoul, 08826, South Korea. biochem.yong@gmail.com., de Guzman ACV; College of Pharmacy, Natural Products Research Institute, Seoul National University, Sillim-Dong, Gwanak-Gu, Seoul, 08826, South Korea. arviecamille@snu.ac.kr.
Jazyk: angličtina
Zdroj: Metabolomics : Official journal of the Metabolomic Society [Metabolomics] 2023 Jun 08; Vol. 19 (6), pp. 58. Date of Electronic Publication: 2023 Jun 08.
DOI: 10.1007/s11306-023-02022-w
Abstrakt: Background and Aims: SKN-1, a C. elegans transcription factor analogous to the mammalian NF-E2-related factor (Nrf2), has been known to promote oxidative stress resistance aiding nematodes' longevity. Although SKN-1's functions suggest its implication in lifespan modulation through cellular metabolism, the actual mechanism of how metabolic rearrangements contribute to SKN-1's lifespan modulation has yet to be well characterized. Therefore, we performed the metabolomic profiling of the short-lived skn-1-knockdown C. elegans.
Methods: We analyzed the metabolic profile of the skn-1-knockdown worms with nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-tandem mass spectrometry (LC-MS/MS) and obtained distinctive metabolomic profiles compared to WT worms. We further extended our study with gene expression analysis to examine the expression level of genes encoding all metabolic enzymes.
Results: A significant increase in the phosphocholine and AMP/ATP ratio, potential biomarkers of aging, was observed, accompanied by a decrease in the transsulfuration metabolites, NADPH/NADP + ratio, and total glutathione (GSHt), which are known to be involved in oxidative stress defense. skn-1-RNAi worms also exhibited an impairment in the phase II detoxification system, confirmed by the lower conversion rate of paracetamol to paracetamol-glutathione. By further examining the transcriptomic profile, we found a decrease in the expression of cbl-1, gpx, T25B9.9, ugt, and gst, which are involved in GSHt and NADPH synthesis as well as in the phase II detoxification system.
Conclusion: Our multi-omics results consistently revealed that the cytoprotective mechanisms, including cellular redox reactions and xenobiotic detoxification system, contribute to the roles of SKN-1/Nrf2 in the lifespan of worms.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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