Oxidative stress is increased in C. elegans models of Huntington’s disease but does not contribute to polyglutamine toxicity phenotypes

Machiela, Emily; Dues, Dylan J.; Senchuk, Megan M.; Raamsdonk, Jeremy M. Van

doi:10.1016/j.nbd.2016.08.008

Cited by 38 publications

(37 citation statements)

References 75 publications

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“…Once samples for all of the independent replicates had been collected, RNA from all of the samples was extracted at the same time. RNA isolation was done as previously described [24]. Note that the RNA samples used for RNA sequencing were completely independent of those used for quantitative real-time RT-PCR.…”

Section: Methodsmentioning

confidence: 99%

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Uncoupling of oxidative stress resistance and lifespan in long-lived isp-1 mitochondrial mutants in Caenorhabditis elegans

Dues

Schaar

Johnson

et al. 2017

Free Radical Biology and Medicine

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Mutations affecting components of the mitochondrial electron transport chain have been shown to increase lifespan in multiple species including the worm Caenorhabditis elegans. While it was originally proposed that decreased generation of reactive oxygen species (ROS) resulting from lower rates of electron transport could account for the observed increase in lifespan, recent evidence indicates that ROS levels are increased in at least some of these long-lived mitochondrial mutants. Here, we show that the long-lived mitochondrial mutant isp-1 worms have increased resistance to oxidative stress. Our results suggest that elevated ROS levels in isp-1 worms cause the activation of multiple stress-response pathways including the mitochondrial unfolded protein response, the SKN-1-mediated stress response, and the hypoxia response. In addition, these worms have increased expression of specific antioxidant enzymes, including a marked upregulation of the inducible superoxide dismutase genes sod-3 and sod-5. Examining the contribution of sod-3 and sod-5 to the oxidative stress resistance in isp-1 worms revealed that loss of either of these genes increased resistance to oxidative stress, but not other forms of stress. Deletion of sod-3 or sod-5 decreased the lifespan of isp-1 worms and further exacerbated their slow physiologic rates. Thus, while deletion of sod-3 and sod-5 genes has little impact on stress resistance, physiologic rates or lifespan in wild-type worms, these genes are required for the longevity of isp-1 worms. Overall, this work shows that the increased resistance to oxidative stress in isp-1 worms does not account for their longevity, and that resistance to oxidative stress can be experimentally dissociated from lifespan.

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Section: Methodsmentioning

confidence: 99%

“…Quantitative Real-Time RT-PCR (qPCR) was performed in two steps as previously described [24]. mRNA was converted to cDNA using a High-Capacity cDNA Reverse Transcription kit (Life Technologies/Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

Uncoupling of oxidative stress resistance and lifespan in long-lived isp-1 mitochondrial mutants in Caenorhabditis elegans

Dues

Schaar

Johnson

et al. 2017

Free Radical Biology and Medicine

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“…In our recent work, we interrogated the role of oxidative stress in HD using the powerful genetics of C. elegans [1]. As in other animal models of HD, we found that HD worm models exhibit increased oxidative stress and multiple phenotypic deficits resulting from polyglutamine toxicity.…”

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confidence: 93%

Oxidative stress in neurodegenerative disease: causation or association?

2017

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“…References in which this protocol was used: Van Raamsdonk and Hekimi, 2009; 2012; Van Raamsdonk et al, 2010; Cooper et al, 2015; Schaar et al, 2015; Dues et al, 2016; Machiela et al, 2016.…”

Section: Methodsmentioning

confidence: 99%

Measuring Oxidative Stress in Caenorhabditis elegans: Paraquat and Juglone Sensitivity Assays

2017

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Oxidative stress has been proposed to be one of the main causes of aging and has been implicated in the pathogenesis of many diseases. Sensitivity to oxidative stress can be measured by quantifying survival following exposure to a reactive oxygen species (ROS)-generating compound such as paraquat or juglone. Sensitivity to oxidative stress is a balance between basal levels of ROS, the ability to detoxify ROS, and the ability to repair ROS-mediated damage.

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Oxidative stress is increased in C. elegans models of Huntington’s disease but does not contribute to polyglutamine toxicity phenotypes

Cited by 38 publications

References 75 publications

Uncoupling of oxidative stress resistance and lifespan in long-lived isp-1 mitochondrial mutants in Caenorhabditis elegans

Uncoupling of oxidative stress resistance and lifespan in long-lived isp-1 mitochondrial mutants in Caenorhabditis elegans

Oxidative stress in neurodegenerative disease: causation or association?

Measuring Oxidative Stress in Caenorhabditis elegans: Paraquat and Juglone Sensitivity Assays

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