A redox-sensitive peroxiredoxin that is important for longevity has tissue- and stress-specific roles in stress resistance

Oláhová, Monika; Taylor, Sarah R.; Khazaipoul, Siavash; Wang, Jinling; Morgan, Brian A.; Matsumoto, Kunihiro; Blackwell, T. Keith; Veal, Elizabeth A.

doi:10.1073/pnas.0805507105

Cited by 147 publications

(155 citation statements)

References 37 publications

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“…Although it may cause oxidative damage, peroxide is also an established signaling molecule, regulating the activity of target proteins by oxidizing specific redox‐sensitive protein thiols (Veal, Day & Morgan, 2007). However, using the oxidation status of the peroxide‐sensitive peroxiredoxin‐2 as a readout (Oláhová et al., 2008), we could find no evidence that fasting increases peroxide levels (data not shown). Alternatively, lipid‐derived ligand(s), including oxidized molecules, may increase NHR‐49 activity, with exposure to organic peroxide or fasting both increasing the levels of such a lipid.…”

Section: Discussionmentioning

confidence: 64%

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NHR‐49/HNF4 integrates regulation of fatty acid metabolism with a protective transcriptional response to oxidative stress and fasting

et al. 2018

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SummaryEndogenous and exogenous stresses elicit transcriptional responses that limit damage and promote cell/organismal survival. Like its mammalian counterparts, hepatocyte nuclear factor 4 (HNF4) and peroxisome proliferator‐activated receptor α (PPARα), Caenorhabditis elegans NHR‐49 is a well‐established regulator of lipid metabolism. Here, we reveal that NHR‐49 is essential to activate a transcriptional response common to organic peroxide and fasting, which includes the pro‐longevity gene fmo‐2/flavin‐containing monooxygenase. These NHR‐49‐dependent, stress‐responsive genes are also upregulated in long‐lived glp‐1/notch receptor mutants, with two of them making critical contributions to the oxidative stress resistance of wild‐type and long‐lived glp‐1 mutants worms. Similar to its role in lipid metabolism, NHR‐49 requires the mediator subunit mdt‐15 to promote stress‐induced gene expression. However, NHR‐49 acts independently from the transcription factor hlh‐30/TFEB that also promotes fmo‐2 expression. We show that activation of the p38 MAPK, PMK‐1, which is important for adaptation to a variety of stresses, is also important for peroxide‐induced expression of a subset of NHR‐49‐dependent genes that includes fmo‐2. However, organic peroxide increases NHR‐49 protein levels, by a posttranscriptional mechanism that does not require PMK‐1 activation. Together, these findings establish a new role for the HNF4/PPARα‐related NHR‐49 as a stress‐activated regulator of cytoprotective gene expression.

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Section: Discussionmentioning

confidence: 64%

“…A total of 3,000 synchronized late L4 animals were washed from plates with M9 or M9 containing 10 m m tBOOH, incubated for 10 min with gentle agitation, and then harvested by centrifugation and levels of PMK‐1 phosphorylation determined as described previously (Oláhová et al., 2008). …”

Section: Methodsmentioning

confidence: 99%

NHR‐49/HNF4 integrates regulation of fatty acid metabolism with a protective transcriptional response to oxidative stress and fasting

et al. 2018

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“…Superoxides are converted to hydrogen peroxide by superoxide dismutases (SOD) followed by a conversion to water by catalases (CTL) or peroxiredoxins (PRDX) (Sies, 2014). The C. elegans genome encodes 5 different superoxide dismutases ( sod‐1 to sod‐5 ), three different catalases ( ctl‐1 to ctl‐3 ), and three peroxiredoxins that are named according to their homology to the mammalian peroxiredoxins, prdx‐2 , prdx‐3, and prdx‐6 (Doonan et al ., 2008; Olahova et al ., 2008; Kumsta et al ., 2011). …”

Section: Resultsmentioning

confidence: 99%

Atypical antidepressants extend lifespan of Caenorhabditis elegans by activation of a non‐cell‐autonomous stress response

et al. 2015

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SummaryOxidative stress has long been associated with aging and has recently been linked to psychiatric disorders, including psychosis and depression. We identified multiple antipsychotics and antidepressants that extend Caenorhabditis elegans lifespan and protect the animal from oxidative stress. Here, we report that atypical antidepressants activate a neuronal mechanism that regulates the response to oxidative stress throughout the animal. While the activation of the oxidative stress response by atypical antidepressants depends on synaptic transmission, the activation by reactive oxygen species does not. Lifespan extension by atypical antidepressants depends on the neuronal oxidative stress response activation mechanism. Neuronal regulation of the oxidative stress response is likely to have evolved as a survival mechanism to protect the organism from oxidative stress, upon detection of adverse or dangerous conditions by the nervous system.

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“…Larval L4-stage animals were washed from plates with M9 buffer containing 5 mM H 2 O 2 , gently agitated at room temperature for 5 min, then washed twice with the M9 buffer before transferred to plates containing 5 mM H 2 O 2 (55). The viability of each animal was assessed at the indicated times by microscopic examination for evidence of either pharyngeal pumping or movement in response to gentle prodding.…”

Section: Oxidative Stress Assaymentioning

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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A redox-sensitive peroxiredoxin that is important for longevity has tissue- and stress-specific roles in stress resistance

Abstract: aging ͉ Caenorhabditis elegans ͉ oxidative stress ͉ signaling ͉ chaperone

Cited by 147 publications

References 37 publications

NHR‐49/HNF4 integrates regulation of fatty acid metabolism with a protective transcriptional response to oxidative stress and fasting

NHR‐49/HNF4 integrates regulation of fatty acid metabolism with a protective transcriptional response to oxidative stress and fasting

Atypical antidepressants extend lifespan of Caenorhabditis elegans by activation of a non‐cell‐autonomous stress response

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

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