Effects of a potent antioxidant, platinum nanoparticle, on the lifespan of Caenorhabditis elegans
Introduction
It is well known that the accumulation of molecular damage caused by free radicals, which are derived from the reactive oxygen species (ROS) side-products of normal metabolic pathways, is a major factor in ageing (Beckman and Ames, 1998, Bokov et al., 2004, Finkel and Holbrook, 2000). ROS oxidize endogenous molecules, such as lipids (Packer, 1992), proteins (Ishii et al., 2002, Stadtman, 1992), and DNA (Beckman and Ames, 1997). Although most organisms have developed antioxidant defense systems, which include superoxide dismutase (SOD), catalase, and glutathione peroxidase (Fridovich, 1995), not all excess ROS are detoxified. In addition, while oxidized molecules are repaired and replaced by biological protective systems, biomolecules are irreversibly oxidized over time. These irreversibly oxidized molecules accumulate, leading to deleterious consequences during ageing (Raha and Robinson, 2000). Thus, the free radical theory of ageing proposed by Harman (1956) has been supported.
The correlation between delayed ageing progression and oxidative stress resistance has been demonstrated in several model organisms (Beckman and Ames, 1998, Orr and Sohal, 1994). Using wild-type N2 Caenorhabditis elegans (C. elegans), it has been shown that vitamin E (Harrington and Harley, 1988), tocotrienols (Adachi and Ishii, 2000), CoQ10 (Ishii et al., 2004), and EGb761, which is an extract of Ginkgo biloba leaves (Wu et al., 2002), can extend the lifespan of the worms by increasing resistance to oxidative stress. These results suggest that exogenous administration of antioxidants can prolong life. Since SOD/catalase mimetics decrease excessive ROS, they appear to extend the lifespan of C. elegans. However, the effect of well-known SOD/catalase mimetic EUK-8 on lifespan is controversial (Keaney and Gems, 2003, Keaney et al., 2004, Melov et al., 2000, Sampayo et al., 2003, Uchiyama et al., 2005). Thus, further clarification of the effects of SOD/catalase mimetics on lifespan is needed.
Recently, polymer-protected metal nanoparticles have been developed. These metal nanoparticles can function as catalysts in various reactions, such as hydrogenation, oxidation, and hydration (Aiken and Finke, 1999, Toshima and Yonezawa, 1998). In biosciences, gold nanoparticles have been primarily used as nanoprobes for transmission electron microscopy (Mannweiler et al., 1982). As platinum nanoparticles (nano-Pt) are known to act as reductive catalysts, they may have utility as antioxidants to reduce ROS in living organisms. Indeed, we have shown that nano-Pt has the ability to scavenge ROS, superoxide anion radicals (O2−), and hydrogen peroxide (H2O2), indicating that in functional terms, nano-Pt can act as a SOD/catalase mimetic (Kajita et al., 2007).
In the present study, we compared the effects of nano-Pt and EUK-8 on the lifespan of C. elegans strains, i.e., the wild-type N2 and the short-lived mev-1(kn1) mutant. We found that nano-Pt was more effective than EUK-8 in extending the lifespan of C. elegans.
Section snippets
C. elegans strains and growth conditions
The wild-type N2 strain and the mev-1(kn1) mutant were provided by the Caenorhabditis Genetic Center (University of Minnesota, St. Paul, MN, USA). These strains were maintained at 20 °C, according to the procedures established by Brenner (1974). Age-synchronous populations were prepared, as previously described (Emmons et al., 1979). Briefly, collected eggs were allowed to hatch overnight at 20 °C in S-basal buffer, which consisted of 100 mM NaCl, 0.01 mM cholesterol, and 50 mM potassium phosphate
Lifespan
The survival curve for N2 worms under normal conditions (Fig. 1A and Table 1) was in good accordance with those reported previously (Keaney et al., 2004, Uchiyama et al., 2005). Treatment with 0.5 mM nano-Pt extended the average lifespan by 22.3 ± 2.8% (p < 0.001), while significant lifespan extension was not observed at other concentrations of nano-Pt (Fig. 1A and C and Table 1). PVP (40 mM) alone did not increase the lifespan. EUK-8 did not prolong, but rather reduced the mean lifespan in a
Discussion
In the present study, we examined the effects of nano-Pt, which is a new SOD/catalase mimetic, on the lifespan of C. elegans strains. In the lifespan assay, at 0.5 mM, nano-Pt extended the lifespan of N2 nematode but at 0.1 and 1 mM, nano-Pt did not (Fig. 1). Cellular damage caused by oxidative stress is one of the key factors in ageing so that we examined whether nano-Pt affect the accumulation of the autofluorescent pigment lipofuscin. Lipofuscin is generated by oxidative degeneration and
References (65)
- et al.
A review of modern transition-metal nanoclusters: their synthesis, characterization, and applications in catalysis
J. Mol. Catal. A Chem.
(1999) - et al.
Effects of superoxide dismutase/catalase mimetics on life span and oxidative stress resistance in the housefly, Musca domestica
Free Radic. Biol. Med.
(2002) - et al.
Oxidative decay of DNA
J. Biol. Chem.
(1997) - et al.
The role of oxidative damage and stress in aging
Mech. Ageing Dev.
(2004) - et al.
Lipofuscin: mechanisms of age-related accumulation and influence on cell function
Free Radic. Biol. Med.
(2002) - et al.
Inside the neurophil phagosome: oxidants, myeloperoxidase, and bacterial killing
Blood
(1998) - et al.
Effects of vitamin E on lifespan and reproduction in Caenorhabditis elegans
Mech. Ageing Dev.
(1988) - et al.
Protein oxidation during aging of the nematode Caenorhabditis elegans
Free Radic. Biol. Med.
(2002) - et al.
Coenzyme Q10 can prolong C. elegans lifespan by lowering oxidative stress
Mech. Ageing Dev.
(2004) - et al.
Synthetic superoxide dismutase/catalase mimetics reduce oxidative stress and prolong survival in a mouse amyotrophic lateral sclerosis model
Neurosci. Lett.
(2001)
Investigations of protective effects of the flavonoids quercetin and rutin on stress resistance in the model organism Caenorhabditis elegans
Toxicology
No increase in lifespan in Caenorhabditis elegans upon treatment with the superoxide dismutase mimetic EUK-8
Free Radic. Biol. Med.
Superoxide dismutase mimetics elevate superoxide dismutase activity in vivo but do not retard aging in the nematode Caenorhabditis elegans
Free Radic. Biol. Med.
The effects of exogenous antioxidants on lifespan and oxidative stress resistance in Drosophila melanogaster
Mech. Ageing Dev.
Mitochondria, oxygen free radicals, disease and aging
Trends Biochem. Sci.
A defect in the cytochrome b large subunit in complex II causes both superoxide anion overproduction and abnormal energy metabolism in Caenorhabditis elegans
J. Biol. Chem.
Effect of quantity of polymer on catalysis and superstructure size of polymer-protected Pt nanoclusters
Inorg. Chim. Acta
Nitrosylation: the prototypic redox-based signaling mechanism
Cell
Ceroid/lipofuscin-loaded human fibroblasts show increased susceptibility to oxidative stress
Exp. Gerontol.
Dietary restriction in C. elegans: from rate-of-living effects to nutrient sensing pathways
Mech. Ageing Dev.
Effects of tocotrienols on life span and protein carbonylation in Caenorhabditis elegans
J. Gerontrol. A Biol. Sci.
Synthetic combined superoxide dismutase/catalase mimetics are protective as a delayed treatment in a rat stroke model: a key role for reactive oxygen species in ischemic brain injury
J. Pharmacol. Exp. Ther.
The free radical theory of aging matures
Physiol. Rev.
The genetics of Caenorhabditis elegans
Genetics
Role of superoxide as a signaling molecule
News Physiol. Sci.
Mitochondria are a major source of paraquat-induced reactive oxygen species production in the brain
J. Biol. Chem.
A proposed refinement of the mitochondrial free radical theory of aging
Bioessays
Analysis of the constancy of DNA sequenced during development and evolution of the nematode Caenorhabditis elegans
Proc. Natl. Acad. Sci. U.S.A.
Oxidants, oxidative stress and the biology of ageing
Nature
Superoxide radical and superoxide dismutases
Annu. Rev. Biochem.
Genetic analysis of tissue aging in Caenorhabditis elegans: a role for heat-shock factor and bacterial proliferation
Genetics
Genetic, behavioral and environmental determinants of male longevity in Caenorhabditis elegans
Genetics
Cited by (0)
- 1
Present address: Department of Aging Control, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
- 2
Present address: Department of Global Infectious Diseases and Tropical Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.