SOD-1 Deletions in Caenorhabditis elegans Alter the Localization of Intracellular Reactive Oxygen Species and Show Molecular Compensation

Yanase, Sumino; Onodera, Akira; Tedesco, Patricia M.; Johnson, Thomas E.; Ishii, Naoaki

doi:10.1093/gerona/glp020

Cited by 70 publications

(60 citation statements)

References 42 publications

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“…S4). As SOD-1 has been observed in the mitochondria (20,27), this suggests the possibility that it is the complete absence of any SOD in the mitochondria that abolishes the positive effect of sod-2 deletion on lifespan.…”

Section: -G)mentioning

confidence: 88%

“…Consistent with the view that superoxide scavenging activity is important for survival, deletion of either cytoplasmic or mitochondrial sod genes in yeast (8)(9)(10)(11), flies (12)(13)(14), and mice (15)(16)(17) results in decreased lifespan (Table 1). In contrast, deletion of individual sod genes has been found to have little or no detrimental effect on lifespan in the roundworm Caenorhabditis elegans (18)(19)(20)(21)(22) (Table 1).…”

mentioning

confidence: 99%

“…Thus, it is possible that the loss of individual SODs is compensated for by the presence of these additional sod genes. In fact, up-regulation of other sod genes has been observed in individual sod deletion mutants (20,22).…”

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confidence: 99%

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Superoxide dismutase is dispensable for normal animal lifespan

Raamsdonk

Hekimi²

2012

Proc. Natl. Acad. Sci. U.S.A.

288

233

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Reactive oxygen species (ROS) are toxic oxygen-containing molecules that can damage multiple components of the cell and have been proposed to be the primary cause of aging. The antioxidant enzyme superoxide dismutase (SOD) is the only eukaryotic enzyme capable of detoxifying superoxide, one type of ROS. The fact that SOD is present in all aerobic organisms raises the question as to whether SOD is absolutely required for animal life and whether the loss of SOD activity will result in decreased lifespan. Here we use the genetic model organism Caenorhabditis elegans to generate an animal that completely lacks SOD activity ( sod-12345 worms). We show that sod-12345 worms are viable and exhibit a normal lifespan, despite markedly increased sensitivity to multiple stresses. This is in stark contrast to what is observed in other genetic model organisms where the loss of a single sod gene can result in severely decreased survival. Investigating the mechanism underlying the normal lifespan of sod-12345 worms reveals that their longevity results from a balance between the prosurvival signaling and the toxicity of superoxide. Overall, our results demonstrate that SOD activity is dispensable for normal animal lifespan but is required to survive acute stresses. Moreover, our findings indicate that maintaining normal stress resistance is not crucial to the rate of aging.

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Section: -G)mentioning

confidence: 88%

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confidence: 99%

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Superoxide dismutase is dispensable for normal animal lifespan

Raamsdonk

Hekimi²

2012

Proc. Natl. Acad. Sci. U.S.A.

288

233

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“…Fujii et al reported that neurons are direct targets of paraquat in C. elegans (30). Like in mammals, C. elegans SOD and glutathione are ubiquitously expressed in many tissues (43)(44)(45)(46)(47)(48). Unlike these antioxidant enzymes, GLB-13 is only expressed in few neuronal cells, although the evidence that how the signals are processed and integrated with other signals to specify oxidative stress is still unclear.…”

Section: Figmentioning

confidence: 99%

GLB‐13 is associated with oxidative stress resistance in caenorhabditis elegans

Ren

Han

et al. 2013

IUBMB Life

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Globins constitute a superfamily of heme-binding proteins that is widely present in many species. There are 33 putative globins in the genome of Caenorhabditis elegans, where glb-13 is a homolog of neuroglobin (Ngb) based on sequence analysis and specific expression in neurons. Here we examined whether glb-13 as well as Ngb is also associated with resistance to reactive oxygen species (ROS) induced by paraquat. Our results showed that the mRNA level of glb-13 was significantly upregulated after paraquat exposure. Expression of a green fluorescent protein (GFP) reporter gene directed by the glb-13 promoter was increased by paraquat exposure. The mutant C. elegans strain glb-13(tm2825) was sensitive to paraquat-induced oxidative stress. Overexpression of human Ngb (hNgb) in C. elegans neuronal cells can rescue the paraquat sensitive phenotype of the mutant strain. glb-13 mutation or hNgb overexpression did not affect the expression of antioxidant enzymes such as superoxide dismutase (SOD). To examine the ROS-scavenging capabilities of hNgb and glb-13, we further examined the level of ROS in glb-13 mutant and hNgb transgenic (hNgb-Tg) worms. There was no statistical difference in ROS levels in the untreated controls; however in paraquattreated worms, the ROS level was statistically repressed in the hNgb-Tg relative to enhanced green fluorescent protein (EGFP)-Tg worms or wildtype animals. Additionally, the ROS level of glb-13 mutant was statistically higher than the wildtype animals. Furthermore, hNgb overexpression diminished the ROS level of glb-13 mutant. In conclusion, hNgb can rescue the ROS sensitive phenotype of the glb-13 mutant strain. The protein GLB-13 seems to have an hNgb-like function, suggesting the importance of the globin protein family in maintaining the homeostasis of ROS signals. Our data provided evidence for the first time that glb-13 is associated with the resistance against oxidative stress-induced toxicity.

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“…The C. elegans homologue of SOD-1 (sod-1) is 56% identical to its human counterpart [83], is widely expressed in most adult tissues [84], and its activity in long-lived mutant strains is upregulated [83,85]. Major sod-1 deletion has no effect on average lifespan under ad libitum and dietary restricted conditions at 25°C; however, at 16°C mutants display significantly reduced longevity compared to wild type [86].…”

Section: Spinal Muscular Atrophymentioning

confidence: 99%

C. elegans models of neuromuscular diseases expedite translational research

Sleigh

Sattelle²

2010

Translational Neuroscience

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The nematode Caenorhabditis elegans is a genetic model organism and the only animal with a complete nervous system wiring diagram. With only 302 neurons and 95 striated muscle cells, a rich array of mutants with defective locomotion and the facility for individual targeted gene knockdown by RNA interference, it lends itself to the exploration of gene function at nerve muscle junctions. With approximately 60% of human disease genes having a C. elegans homologue, there is growing interest in the deployment of lowcost, high-throughput, drug screens of nematode transgenic and mutant strains mimicking aspects of the pathology of devastating human neuromuscular disorders. Here we explore the contributions already made by C. elegans to our understanding of muscular dystrophies (Duchenne and Becker), spinal muscular atrophy, amyotrophic lateral sclerosis, Friedreich’s ataxia, inclusion body myositis and the prospects for contributions to other neuromuscular disorders. A bottleneck to low-cost, in vivo, large-scale chemical library screening for new candidate therapies has been rapid, automated, behavioural phenotyping. Recent progress in quantifying simple swimming (thrashing) movements is making such screening possible and is expediting the translation of drug candidates towards the clinic.

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SOD-1 Deletions in Caenorhabditis elegans Alter the Localization of Intracellular Reactive Oxygen Species and Show Molecular Compensation

Cited by 70 publications

References 42 publications

Superoxide dismutase is dispensable for normal animal lifespan

Superoxide dismutase is dispensable for normal animal lifespan

GLB‐13 is associated with oxidative stress resistance in caenorhabditis elegans

C. elegans models of neuromuscular diseases expedite translational research

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