Enhanced ROS production leads to excessive fat accumulation through DAF-16 in Caenorhabditis elegans

Wang, Kejie; Chen, Sixi; Zhang, Congjie; Huang, Jiatao; Wu, Juan; Zhou, Huaibin; Jin, Liqin; Xu, Qian; Jin, Jinlong; Lyu, Jianxin

doi:10.1016/j.exger.2018.07.017

Cited by 31 publications

(24 citation statements)

References 45 publications

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“…To validate an increased ROS generation by PQ as the reason for mitochondrial dysfunction, we investigated mitochondrial and also cytosolic ROS levels. Since PQ treatment for 48 h decreased intestinal pumping of nematodes causing an insufficient uptake of both fluorescent markers (data not shown), we had to decrease the time of exposure to 4 h. Nevertheless, also after this short incubation period, ROS levels at both locations were significantly increased which is in line with previous findings [14, 58, 59, 80, 81].…”

Section: Discussionsupporting

confidence: 87%

Mitochondrial Oxidative Stress Impairs Energy Metabolism and Reduces Stress Resistance and Longevity ofC. elegans

Dilberger

Baumanns

Schmitt

et al. 2019

Oxidative Medicine and Cellular Longevity

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Introduction Mitochondria supply cellular energy and are key regulators of intrinsic cell death and consequently affect longevity. The nematode Caenorhabditis elegans is frequently used for lifespan assays. Using paraquat (PQ) as a generator of reactive oxygen species, we here describe its effects on the acceleration of aging and the associated dysfunctions at the level of mitochondria. Methods Nematodes were incubated with various concentrations of paraquat in a heat-stress resistance assay (37°C) using nucleic staining. The most effective concentration was validated under physiological conditions, and chemotaxis was assayed. Mitochondrial membrane potential (ΔΨm) was measured using rhodamine 123, and activity of respiratory chain complexes determined using a Clark-type electrode in isolated mitochondria. Energetic metabolites in the form of pyruvate, lactate, and ATP were determined using commercial kits. Mitochondrial integrity and structure was investigated using transmission electron microscopy. Live imaging after staining with fluorescent dyes was used to measure mitochondrial and cytosolic ROS. Expression of longevity- and mitogenesis-related genes were evaluated using qRT-PCR. Results PQ (5 mM) significantly increased ROS formation in nematodes and reduced the chemotaxis, the physiological lifespan, and the survival in assays for heat-stress resistance. The number of fragmented mitochondria significantly increased. The ∆Ψm, the activities of complexes I-IV of the mitochondrial respiratory chain, and the levels of pyruvate and lactate were significantly reduced, whereas ATP production was not affected. Transcript levels of genetic marker genes, atfs-1, atp-2, skn-1, and sir-2.1, were significantly upregulated after PQ incubation, which implicates a close connection between mitochondrial dysfunction and oxidative stress response. Expression levels of aak-2 and daf-16 were unchanged. Conclusion Using paraquat as a stressor, we here describe the association of oxidative stress, restricted energy metabolism, and reduced stress resistance and longevity in the nematode Caenorhabditis elegans making it a readily accessible in vivo model for mitochondrial dysfunction.

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Section: Discussionsupporting

confidence: 87%

Mitochondrial Oxidative Stress Impairs Energy Metabolism and Reduces Stress Resistance and Longevity ofC. elegans

Dilberger

Baumanns

Schmitt

et al. 2019

Oxidative Medicine and Cellular Longevity

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“…As based on our own experience, the animals can be moved with 80 μl of liquid. In both protocols and Wang et al (2018) suggest adding an indicator to the sample after lysis, but in our tests, it was found that too much time elapses between incubation and measurement. Consequently, animals still alive can degrade the produced reactive oxygen species.…”

Section: Evaluation Of Reactive Oxygen Species Generation Methodsmentioning

confidence: 74%

Toxicity mitigation by N-acetylcysteine and synergistic toxic effect of nano and bulk ZnO to Panagrellus redivivus

Kiss

Sávoly²,

Ács

et al. 2021

Environ Sci Pollut Res

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To better understand the nanosize-relevant toxic effects and underlying mechanisms, N-acetylcysteine (NAC), as a mitigation agent, an ionic form of Zn (ZnCl2), and the binary mixture of ZnO with different particle sizes (15 nm and 140 nm), was used in toxicity assays with the nematode Panagrellus redivivus. The ZnCl2 concentrations were applied to show the amount of dissolved Zn ions present in the test system. Reactive oxygen species (ROS) measuring method was developed to fit the used test system. Our studies have shown that NAC can mitigate the toxic effects of both studied particle sizes. In the applied concentrations, ZnCl2 was less toxic than both of the ZnO particles. This finding indicates that not only ions and ROS produced by the dissolution are behind the toxic effects of the ZnO NPs, but also other particle size-dependent toxic effects, like the spontaneous ROS generation, are also relevant. When the two materials were applied in binary mixtures, the toxic effects increased significantly, and the dissolved zinc content and the ROS generation also increased. It is assumed that the chemical and physical properties of the materials have been mutually reinforcing to form a more reactive mixture that is more toxic to the P. redivivus test organism. Our findings demonstrate the importance of using mitigation agent and mixtures to evaluate the size-dependent toxicity of the ZnO. Graphical abstract

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“…It has been demonstrated that the accumulation of fat promotes the generation of ROS, and increased ROS production contributes to an excessive accumulation of fat [ 49 ]. Considering the anti-oxidative stress capacity, the effects of SePs on fat accumulation, ROS, and MDA levels in high-fat worms was examined.…”

Section: Resultsmentioning

confidence: 99%

Antioxidant Peptides from Sepia esculenta Hydrolyzate Attenuate Oxidative Stress and Fat Accumulation in Caenorhabditis elegans

Shen

et al. 2020

Marine Drugs

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The hydrolysate of golden cuttlefish (Sepia esculenta) was prepared by using papain, and then, it was further separated by ultrafiltration, gel filtration chromatography, and reverse-phase high-performance liquid chromatography (RP-HPLC). The peptide components of the active fraction were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and then two novel peptides, SeP2 (DVEDLEAGLAK, 1159.27 Da) and SeP5 (EITSLAPSTM, 1049.22 Da), were obtained and displayed significant alleviation effects on oxidative stress in Caenorhabditis elegans. Studies indicated that S. esculenta antioxidant peptides (SePs) increase superoxide dismutase (SOD) activity but reduce reactive oxygen species (ROS) and malondialdehyde (MDA) levelsin oxidation-damaged nematodes. Using transgenic CF1553 nematodes, the sod-3p::GFP expression in the worms treated with SePs was significantly higher than that of the control nematodes. Real-time PCR also demonstrated that the expression of stress-related genes such as sod-3 is up-regulated by SePs. Furthermore, studies showed that SePs could obviously decrease fat accumulation as well as reduce the elevated ROS and MDA levels in high-fat nematodes. Taken together, these results indicated that SePs are capable of the activation of antioxidant defense and the inhibition of free radicals and lipid peroxidation, play important roles in attenuating oxidative stress and fat accumulation in C. elegans, and might have the potential to be used in nutraceutical and functional foods.

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Enhanced ROS production leads to excessive fat accumulation through DAF-16 in Caenorhabditis elegans

Cited by 31 publications

References 45 publications

Mitochondrial Oxidative Stress Impairs Energy Metabolism and Reduces Stress Resistance and Longevity ofC. elegans

Mitochondrial Oxidative Stress Impairs Energy Metabolism and Reduces Stress Resistance and Longevity ofC. elegans

Toxicity mitigation by N-acetylcysteine and synergistic toxic effect of nano and bulk ZnO to Panagrellus redivivus

Antioxidant Peptides from Sepia esculenta Hydrolyzate Attenuate Oxidative Stress and Fat Accumulation in Caenorhabditis elegans

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