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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

ART, SNP, ARG, H2O2, or CR activates antioxidant networks for ROS scavenging.(A) and (B) ELISA measurement of time-dependently induced mitochondria-localized Mn-SOD and SIRT3 by CR and mimetics. (C), (D), and (E) ELISA measurement of time-dependently induced SOD, CAT, and GSH by CR and mimetics. (F) ELISA measurement of the total ROS level in mice treated by CR and mimetics. 0 h represents AL; 3 m indicates CR for three months; and 1 h, 3 h, or 6 h means treatment for one hour, three hours, or six hours. ART (260 µM), SNP (67 µM), ARG (5.7 mM), or H2O2(200 µM) was injected into the mouse skeletal muscle in the dose of 50 µl volume/20 g body weight. The 1 h, 3 h, or 6 h group had only one injection, and the 3d group had three daily injections. The ages of mice used are two-month-old except for CR mice, which are four-month-old with one-month AL and three-month CR treatment. The significance of statistical difference between a treatment sample and the AL sample was represented by * P < 0.05; ** P < 0.01; *** P < 0.001 (n = 3).
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fig-2: ART, SNP, ARG, H2O2, or CR activates antioxidant networks for ROS scavenging.(A) and (B) ELISA measurement of time-dependently induced mitochondria-localized Mn-SOD and SIRT3 by CR and mimetics. (C), (D), and (E) ELISA measurement of time-dependently induced SOD, CAT, and GSH by CR and mimetics. (F) ELISA measurement of the total ROS level in mice treated by CR and mimetics. 0 h represents AL; 3 m indicates CR for three months; and 1 h, 3 h, or 6 h means treatment for one hour, three hours, or six hours. ART (260 µM), SNP (67 µM), ARG (5.7 mM), or H2O2(200 µM) was injected into the mouse skeletal muscle in the dose of 50 µl volume/20 g body weight. The 1 h, 3 h, or 6 h group had only one injection, and the 3d group had three daily injections. The ages of mice used are two-month-old except for CR mice, which are four-month-old with one-month AL and three-month CR treatment. The significance of statistical difference between a treatment sample and the AL sample was represented by * P < 0.05; ** P < 0.01; *** P < 0.001 (n = 3).

Mentions: To reveal the effects of CR-triggered NO and H2O2 on the oxidative and antioxidative homeostasis, we monitored the dynamic changes of mitochondrial manganese superoxide dismutase (Mn-SOD, SOD2) and its activator SIRT3 in the skeletal muscle cells of mice treated by CR and mimetics. Consequently, both Mn-SOD (Fig. 2A) and SIRT3 (Fig. 2B) are synchronously up-regulated in a time-dependent manner after exposure to CR or injection by ART, SNP, ARG, or H2O2. While ARG induces the highest Mn-SOD quantity, SNP induces the highest SIRT3 quantity. These results demonstrate that antioxidation against oxidation is initiated from the activation of SIRT3-SOD2 in mitochondria of skeletal muscle cells after treatment of mice by CR and mimetics.


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)

ART, SNP, ARG, H2O2, or CR activates antioxidant networks for ROS scavenging.(A) and (B) ELISA measurement of time-dependently induced mitochondria-localized Mn-SOD and SIRT3 by CR and mimetics. (C), (D), and (E) ELISA measurement of time-dependently induced SOD, CAT, and GSH by CR and mimetics. (F) ELISA measurement of the total ROS level in mice treated by CR and mimetics. 0 h represents AL; 3 m indicates CR for three months; and 1 h, 3 h, or 6 h means treatment for one hour, three hours, or six hours. ART (260 µM), SNP (67 µM), ARG (5.7 mM), or H2O2(200 µM) was injected into the mouse skeletal muscle in the dose of 50 µl volume/20 g body weight. The 1 h, 3 h, or 6 h group had only one injection, and the 3d group had three daily injections. The ages of mice used are two-month-old except for CR mice, which are four-month-old with one-month AL and three-month CR treatment. The significance of statistical difference between a treatment sample and the AL sample was represented by * P < 0.05; ** P < 0.01; *** P < 0.001 (n = 3).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig-2: ART, SNP, ARG, H2O2, or CR activates antioxidant networks for ROS scavenging.(A) and (B) ELISA measurement of time-dependently induced mitochondria-localized Mn-SOD and SIRT3 by CR and mimetics. (C), (D), and (E) ELISA measurement of time-dependently induced SOD, CAT, and GSH by CR and mimetics. (F) ELISA measurement of the total ROS level in mice treated by CR and mimetics. 0 h represents AL; 3 m indicates CR for three months; and 1 h, 3 h, or 6 h means treatment for one hour, three hours, or six hours. ART (260 µM), SNP (67 µM), ARG (5.7 mM), or H2O2(200 µM) was injected into the mouse skeletal muscle in the dose of 50 µl volume/20 g body weight. The 1 h, 3 h, or 6 h group had only one injection, and the 3d group had three daily injections. The ages of mice used are two-month-old except for CR mice, which are four-month-old with one-month AL and three-month CR treatment. The significance of statistical difference between a treatment sample and the AL sample was represented by * P < 0.05; ** P < 0.01; *** P < 0.001 (n = 3).
Mentions: To reveal the effects of CR-triggered NO and H2O2 on the oxidative and antioxidative homeostasis, we monitored the dynamic changes of mitochondrial manganese superoxide dismutase (Mn-SOD, SOD2) and its activator SIRT3 in the skeletal muscle cells of mice treated by CR and mimetics. Consequently, both Mn-SOD (Fig. 2A) and SIRT3 (Fig. 2B) are synchronously up-regulated in a time-dependent manner after exposure to CR or injection by ART, SNP, ARG, or H2O2. While ARG induces the highest Mn-SOD quantity, SNP induces the highest SIRT3 quantity. These results demonstrate that antioxidation against oxidation is initiated from the activation of SIRT3-SOD2 in mitochondria of skeletal muscle cells after treatment of mice by CR and mimetics.

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