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Artemisinin mimics calorie restriction to trigger mitochondrial biogenesis and compromise telomere shortening in mice.

Wang DT, He J, Wu M, Li SM, Gao Q, Zeng QP - PeerJ (2015)

Bottom Line: Calorie restriction is known to extend lifespan among organisms by a debating mechanism underlying nitric oxide-driven mitochondrial biogenesis.We report here that nitric oxide generators including artemisinin, sodium nitroprusside, and L-arginine mimics calorie restriction and resembles hydrogen peroxide to initiate the nitric oxide signaling cascades and elicit the global antioxidative responses in mice.In conclusion, calorie restriction-triggered nitric oxide provides antioxidative protection and alleviates telomere attrition via mitochondrial biogenesis, thereby maintaining chromosomal stability and integrity, which are the hallmarks of longevity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Tropical Medicine Institute, Guangzhou University of Chinese Medicine , Guangzhou , China.

ABSTRACT
Calorie restriction is known to extend lifespan among organisms by a debating mechanism underlying nitric oxide-driven mitochondrial biogenesis. We report here that nitric oxide generators including artemisinin, sodium nitroprusside, and L-arginine mimics calorie restriction and resembles hydrogen peroxide to initiate the nitric oxide signaling cascades and elicit the global antioxidative responses in mice. The large quantities of antioxidant enzymes are correlated with the low levels of reactive oxygen species, which allow the down-regulation of tumor suppressors and accessory DNA repair partners, eventually leading to the compromise of telomere shortening. Accompanying with the up-regulation of signal transducers and respiratory chain signatures, mitochondrial biogenesis occurs with the elevation of adenosine triphosphate levels upon exposure of mouse skeletal muscles to the mimetics of calorie restriction. In conclusion, calorie restriction-triggered nitric oxide provides antioxidative protection and alleviates telomere attrition via mitochondrial biogenesis, thereby maintaining chromosomal stability and integrity, which are the hallmarks of longevity.

No MeSH data available.


Related in: MedlinePlus

Western blotting of target proteins in mouse skeletal muscles injected by ART, SNP, or ARG.(A) Up-regulation and phosphorylation of eNOS and upstream protein kinases. (B) Up-regulation of mitochondrial biomarkers and relevant signal transducers. (C) The time-course mode of up-regulation of signal transducers and mitochondrial biomarkers. Western blotting was performed after three days of daily injection by 260 µM ART, 67 µM SNP, or 5.7 mM ARG (50 µl volume/20 g body weight). For each group of blots, only one stripe of gel with GAPDH bands was shown as reference, but blotting of each target protein was parallelly performed with GAPDH for comparison.
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fig-6: Western blotting of target proteins in mouse skeletal muscles injected by ART, SNP, or ARG.(A) Up-regulation and phosphorylation of eNOS and upstream protein kinases. (B) Up-regulation of mitochondrial biomarkers and relevant signal transducers. (C) The time-course mode of up-regulation of signal transducers and mitochondrial biomarkers. Western blotting was performed after three days of daily injection by 260 µM ART, 67 µM SNP, or 5.7 mM ARG (50 µl volume/20 g body weight). For each group of blots, only one stripe of gel with GAPDH bands was shown as reference, but blotting of each target protein was parallelly performed with GAPDH for comparison.

Mentions: To ascertain the possibility of ART, SNP, or ARG mediating NO signaling, we evaluated the expression and phosphorylation of eNOS and its upstream protein kinases, including Akt and AMPK. As results, their non-phosphorylated/phosphorylated forms, AMPK and p-AMPKThr172, Akt and p-AktSer473, and eNOS and p-eNOSSer1177, are simultaneously induced in the skeletal muscle cells of mice injected by ART, SNP, or ARG (Fig. 6A and Table 4). AMPK and p-AMPKThr172 exhibit almost identical expression levels, suggesting a synchronous mode of AMPK expression and phosphorylation. Akt and eNOS show higher levels than p-AktSer473 and p-eNOSSer1177, implying only a minor of Akt and eNOS being phosphorylated. These results indicate that ART, SNP, or ARG can synchronously induce eNOS, Akt, and AMPK, and partially activate them into p-eNOSSer1177, p-AktSer473, and p-AMPKThr172.


Artemisinin mimics calorie restriction to trigger mitochondrial biogenesis and compromise telomere shortening in mice.

Wang DT, He J, Wu M, Li SM, Gao Q, Zeng QP - PeerJ (2015)

Western blotting of target proteins in mouse skeletal muscles injected by ART, SNP, or ARG.(A) Up-regulation and phosphorylation of eNOS and upstream protein kinases. (B) Up-regulation of mitochondrial biomarkers and relevant signal transducers. (C) The time-course mode of up-regulation of signal transducers and mitochondrial biomarkers. Western blotting was performed after three days of daily injection by 260 µM ART, 67 µM SNP, or 5.7 mM ARG (50 µl volume/20 g body weight). For each group of blots, only one stripe of gel with GAPDH bands was shown as reference, but blotting of each target protein was parallelly performed with GAPDH for comparison.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4358698&req=5

fig-6: Western blotting of target proteins in mouse skeletal muscles injected by ART, SNP, or ARG.(A) Up-regulation and phosphorylation of eNOS and upstream protein kinases. (B) Up-regulation of mitochondrial biomarkers and relevant signal transducers. (C) The time-course mode of up-regulation of signal transducers and mitochondrial biomarkers. Western blotting was performed after three days of daily injection by 260 µM ART, 67 µM SNP, or 5.7 mM ARG (50 µl volume/20 g body weight). For each group of blots, only one stripe of gel with GAPDH bands was shown as reference, but blotting of each target protein was parallelly performed with GAPDH for comparison.
Mentions: To ascertain the possibility of ART, SNP, or ARG mediating NO signaling, we evaluated the expression and phosphorylation of eNOS and its upstream protein kinases, including Akt and AMPK. As results, their non-phosphorylated/phosphorylated forms, AMPK and p-AMPKThr172, Akt and p-AktSer473, and eNOS and p-eNOSSer1177, are simultaneously induced in the skeletal muscle cells of mice injected by ART, SNP, or ARG (Fig. 6A and Table 4). AMPK and p-AMPKThr172 exhibit almost identical expression levels, suggesting a synchronous mode of AMPK expression and phosphorylation. Akt and eNOS show higher levels than p-AktSer473 and p-eNOSSer1177, implying only a minor of Akt and eNOS being phosphorylated. These results indicate that ART, SNP, or ARG can synchronously induce eNOS, Akt, and AMPK, and partially activate them into p-eNOSSer1177, p-AktSer473, and p-AMPKThr172.

Bottom Line: Calorie restriction is known to extend lifespan among organisms by a debating mechanism underlying nitric oxide-driven mitochondrial biogenesis.We report here that nitric oxide generators including artemisinin, sodium nitroprusside, and L-arginine mimics calorie restriction and resembles hydrogen peroxide to initiate the nitric oxide signaling cascades and elicit the global antioxidative responses in mice.In conclusion, calorie restriction-triggered nitric oxide provides antioxidative protection and alleviates telomere attrition via mitochondrial biogenesis, thereby maintaining chromosomal stability and integrity, which are the hallmarks of longevity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Tropical Medicine Institute, Guangzhou University of Chinese Medicine , Guangzhou , China.

ABSTRACT
Calorie restriction is known to extend lifespan among organisms by a debating mechanism underlying nitric oxide-driven mitochondrial biogenesis. We report here that nitric oxide generators including artemisinin, sodium nitroprusside, and L-arginine mimics calorie restriction and resembles hydrogen peroxide to initiate the nitric oxide signaling cascades and elicit the global antioxidative responses in mice. The large quantities of antioxidant enzymes are correlated with the low levels of reactive oxygen species, which allow the down-regulation of tumor suppressors and accessory DNA repair partners, eventually leading to the compromise of telomere shortening. Accompanying with the up-regulation of signal transducers and respiratory chain signatures, mitochondrial biogenesis occurs with the elevation of adenosine triphosphate levels upon exposure of mouse skeletal muscles to the mimetics of calorie restriction. In conclusion, calorie restriction-triggered nitric oxide provides antioxidative protection and alleviates telomere attrition via mitochondrial biogenesis, thereby maintaining chromosomal stability and integrity, which are the hallmarks of longevity.

No MeSH data available.


Related in: MedlinePlus