Artemisinin mimics calorie restriction to initiate antioxidative responses and compromise telomere shortening
- Published
- Accepted
- Subject Areas
- Biochemistry, Genomics, Pharmacology
- Keywords
- Artemisinin, Calorie restriction, Nitric oxide, Hydrogen peroxide, BRCA1, Telomere
- Copyright
- © 2014 Wang et al.
- Licence
- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ PrePrints) and either DOI or URL of the article must be cited.
- Cite this article
- 2014. Artemisinin mimics calorie restriction to initiate antioxidative responses and compromise telomere shortening. PeerJ PrePrints 2:e565v1 https://doi.org/10.7287/peerj.preprints.565v1
Abstract
Calorie restriction (CR) is known to extend lifespan among organisms with the putative mechanism underlying nitric oxide (NO)-enhanced mitochondrial biogenesis. However, whether NO maintains telomere intact that is implicated in life expectancy remains unknown. We report here the artemisinin derivative artesunate in a low concentration up-regulates mitochondrial SIRT3-SOD2 expression among global activation of antioxidative networks via the NO signaling cascade AMPK→Akt→eNOS→SIRT1→PGC-1α. While the NO donor sodium nitroprusside and the NO precursor L-arginine replicate the antioxidative responses, exogenous low-dose hydrogen peroxide also leads to attenuated oxidative stress. The tumor suppressor BRCA1 and other DNA repair partners are down-regulated after scavenging of reactive oxygen species. Upon treatment, telomere shortening is damped without telomerase up-regulation, highlighting telomere maintenance rather than telomere elongation. In conclusion, artesunate can mimic CR to activate antioxidative responses and alleviate telomere attrition via NO signaling, thereby maintaining the stability and integrity of chromosomes, which are the hallmarks of longevity.
Author Comment
This preprint will be submitted to PeerJ for peer review.
Supplemental Information
Table S1 Microarray of 84 ubiquitylation pathway genes in mouse skeletal muscles treated by ART
Fold changes were calculated from the comparison of ART with AL.
Table S2 Microarray of 84 ubiquitylation pathway genes in mouse skeletal muscles treated by SNP
Fold changes were calculated from the comparison of SNP with AL.
Table S3 Microarray of 84 ubiquitylation pathway genes in mouse skeletal muscles treated by ARG
Fold changes were calculated from the comparison of ARG with AL.
Table S4 Microarray of 84 ubiquitylation pathway genes in mouse skeletal muscles treated by H2O2
Fold changes were calculated from the comparison of H2O2 with AL.
Table S5 Microarray of 84 ubiquitylation pathway genes in mouse skeletal muscles treated by CR
Fold changes were calculated from the comparison of CR with AL.