scholarly journals Oxidative Stress Resistance and Viability of C. elegans in the Presence of Manganese through SKN-1 Protein Expression

Author(s):  
Lauren Accacia Sequeira

Oxidative stress plays an imperative role in viewing how humans respond to diseases, such as diabetes and cancer, as well as in the process of aging. Through research and experimentation of Caenorhabditis elegans, scientists can study organismal and cellular aging that is analogous to that of humans. C. elegans are used as an ideal model of study due to their eukaryotic existence, as well as the relative ease of development and growth protocol. Through C. elegans, researchers can examine relevant signaling pathways, such as those that regulate metabolism, nutrition, and stress responses. As the complete genome for C. elegans has been identified, researchers known the exact cell differentiation pattern of each cell, therefore allowing for in depth study about the responses of C. elegans to different conditions and stresses. The SKN-1 protein in this species initiates development of the digestive tracts and other mesendodermal tissues during the primary stages of C. elegans development. By studying the genetic mechanisms that are rooted in C. elegans aging, humans have the opportunity to identify new human genes, as well as the pathways associated with both disease and aging in humans.

2021 ◽  
pp. 1-17
Author(s):  
Mani Iyer Prasanth ◽  
James Michael Brimson ◽  
Dicson Sheeja Malar ◽  
Anchalee Prasansuklab ◽  
Tewin Tencomnao

BACKGROUND: Streblus asper Lour., has been reported to have anti-aging and neuroprotective efficacies in vitro. OBJECTIVE: To analyze the anti-aging, anti-photoaging and neuroprotective efficacies of S. asper in Caenorhabditis elegans. METHODS: C. elegans (wild type and gene specific mutants) were treated with S. asper extract and analyzed for lifespan and other health benefits through physiological assays, fluorescence microscopy, qPCR and Western blot. RESULTS: The plant extract was found to increase the lifespan, reduce the accumulation of lipofuscin and modulate the expression of candidate genes. It could extend the lifespan of both daf-16 and daf-2 mutants whereas the pmk-1 mutant showed no effect. The activation of skn-1 was observed in skn-1::GFP transgenic strain and in qPCR expression. Further, the extract can extend the lifespan of UV-A exposed nematodes along with reducing ROS levels. Additionally, the extract also extends lifespan and reduces paralysis in Aβ transgenic strain, apart from reducing Aβ expression. CONCLUSIONS: S. asper was able to extend the lifespan and healthspan of C. elegans which was independent of DAF-16 pathway but dependent on SKN-1 and MAPK which could play a vital role in eliciting the anti-aging, anti-photoaging and neuroprotective effects, as the extract could impart oxidative stress resistance and neuroprotection.


Exposome ◽  
2021 ◽  
Author(s):  
Karthik Suresh Arulalan ◽  
Javier Huayta ◽  
Jonathan W Stallrich ◽  
Adriana San-Miguel

Abstract Chemical agents released into the environment can induce oxidative stress in organisms, which is detrimental for health. Although environmental exposures typically include multiple chemicals, organismal studies on oxidative stress derived from chemical agents commonly study exposures to individual compounds. In this work, we explore how chemical mixtures drive the oxidative stress response under various conditions in the nematode C. elegans, by quantitatively assessing levels of gst-4 expression. Our results indicate that naphthoquinone mixtures drive responses differently than individual components, and that altering environmental conditions, such as increased heat and reduced food availability, result in dramatically different oxidative stress responses mounted by C. elegans. When exposed to heat, the oxidative stress response is diminished. Notably, when exposed to limited food, the oxidative stress response specific to juglone is significantly heightened, while identified antagonistic interactions between some naphthoquinone components in mixtures are abolished. This implies that organismal responses to xenobiotics is confounded by environment and stressor interactions. Given the high number of variables under study, and their potential combinations, a simplex centroid design was used to capture such non-trivial response over the design space. This makes the case for the adoption of Design of Experiments approaches as they can greatly expand the experimental space probed in noisy biological readouts, and in combinatorial experiments. Our results also reveal gaps in our current knowledge of the organismal oxidative stress response, which can be addressed by employing sophisticated design of experiments approaches to identify significant interactions.


HortScience ◽  
2005 ◽  
Vol 40 (4) ◽  
pp. 1036E-1037
Author(s):  
Mohamed Tawfik ◽  
Alejandra Ferenczi ◽  
Daniel Enter ◽  
Rebecca Grumet

Abiotic stresses (e.g., salinity, drought, cold, oxidative stress) can be major factors limiting plant productivity worldwide. We sought to increase abiotic stress resistance in cucumber by expressing the A. thaliana transcription factors CBF1and CBF3, which regulate genes responsible for enhanced dehydration-stress resistance in Arabidopsis. Our previous studies in the greenhouse and field demonstrated increased salinity tolerance in CBF-expressing cucumber lines. In the current studies, we tested response of CBF-cucumber plants to drought, chilling, and oxidative stresses. Transgenic cucumber plants subjected to drought stress in the greenhouse showed elevated levels of the stress-inducible compatible solute, proline, compared to the nontransgenic controls. Preliminary results also indicate greater photochemical efficiency in CBF-expressing plants under drought stress conditions compared to the nontransgenic controls. Under nonstressed conditions, there were no significant differences in growth between the transgenic and the nontransgenic cucumber plants; however, after a cycle of drought stress, CBF-cucumber lines had less growth reduction compared to the nontransgenic counterparts. The advantage in growth was less pronounced after a second cycle of drought. We also evaluated the transgenic cucumber plants under chilling conditions (i.e., low, nonfreezing temperatures within the 0 to 12 °C range). Based on plant height and cotyledon and leaf damage measurements, transgenic cucumber seedlings did not show chilling tolerance compared to the wild-type control. The response of transgenic CBF-cucumber plants to oxidative stress using methyl viologen is also being evaluated.


2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Franciny Aparecida Paiva ◽  
Larissa de Freitas Bonomo ◽  
Patrícia Ferreira Boasquivis ◽  
Igor Thadeu Borges Raposo de Paula ◽  
Joyce Ferreira da Costa Guerra ◽  
...  

Carqueja (Baccharis trimera) is a native plant found throughout South America. Several studies have shown that Carqueja has antioxidant activityin vitro, as well as anti-inflammatory, antidiabetic, analgesic, antihepatotoxic, and antimutagenic properties. However, studies regarding its antioxidant potentialin vivoare limited. In this study, we usedCaenorhabditis elegansas a model to examine the antioxidant effects of a Carqueja hydroalcoholic extract (CHE) on stress resistance and lifespan and to investigate whether CHE has a protective effect in aC. elegansmodel for Alzheimer's disease. Here, we show for the first time, usingin vivoassays, that CHE treatment improved oxidative stress resistance by increasing survival rate and by reducing ROS levels under oxidative stress conditions independently of the stress-related signaling pathways (p38, JNK, and ERK) and transcription factors (SKN-1/Nrf and DAF-16/Foxo) tested here. CHE treatment also increased the defenses againstβ-amyloid toxicity inC. elegans, in part by increasing proteasome activity and the expression of two heat shock protein genes. Our findings suggest a potential neuroprotective use for Carqueja, supporting the idea that dietary antioxidants are a promising approach to boost the defensive systems against stress and neurodegeneration.


2009 ◽  
Vol 20 (22) ◽  
pp. 4845-4855 ◽  
Author(s):  
Alexandra Rodaki ◽  
Iryna M. Bohovych ◽  
Brice Enjalbert ◽  
Tim Young ◽  
Frank C. Odds ◽  
...  

Metabolic adaptation, and in particular the modulation of carbon assimilatory pathways during disease progression, is thought to contribute to the pathogenicity of Candida albicans. Therefore, we have examined the global impact of glucose upon the C. albicans transcriptome, testing the sensitivity of this pathogen to wide-ranging glucose levels (0.01, 0.1, and 1.0%). We show that, like Saccharomyces cerevisiae, C. albicans is exquisitely sensitive to glucose, regulating central metabolic genes even in response to 0.01% glucose. This indicates that glucose concentrations in the bloodstream (approximate range 0.05–0.1%) have a significant impact upon C. albicans gene regulation. However, in contrast to S. cerevisiae where glucose down-regulates stress responses, some stress genes were induced by glucose in C. albicans. This was reflected in elevated resistance to oxidative and cationic stresses and resistance to an azole antifungal agent. Cap1 and Hog1 probably mediate glucose-enhanced resistance to oxidative stress, but neither is essential for this effect. However, Hog1 is phosphorylated in response to glucose and is essential for glucose-enhanced resistance to cationic stress. The data suggest that, upon entering the bloodstream, C. albicans cells respond to glucose increasing their resistance to the oxidative and cationic stresses central to the armory of immunoprotective phagocytic cells.


Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1517
Author(s):  
Sofia M. Gutierrez-Zetina ◽  
Susana González-Manzano ◽  
Begoña Ayuda-Durán ◽  
Celestino Santos-Buelga ◽  
Ana M. González-Paramás

Caffeic and dihydrocaffeic acid are relevant microbial catabolites, being described as products from the degradation of different phenolic compounds i.e., hydroxycinnamoyl derivatives, anthocyanins or flavonols. Furthermore, caffeic acid is found both in free and esterified forms in many fruits and in high concentrations in coffee. These phenolic acids may be responsible for a part of the bioactivity associated with the intake of phenolic compounds. With the aim of progressing in the knowledge of the health effects and mechanisms of action of dietary phenolics, the model nematode Caenorhabditis elegans has been used to evaluate the influence of caffeic and dihydrocaffeic acids on lifespan and the oxidative stress resistance. The involvement of different genes and transcription factors related to longevity and stress resistance in the response to these phenolic acids has also been explored. Caffeic acid (CA, 200 μM) and dihydrocaffeic acid (DHCA, 300 μM) induced an increase in the survival rate of C. elegans under thermal stress. Both compounds also increased the mean and maximum lifespan of the nematode, compared to untreated worms. In general, treatment with these acids led to a reduction in intracellular ROS concentrations, although not always significant. Results of gene expression studies conducted by RT-qPCR showed that the favorable effects of CA and DHCA on oxidative stress and longevity involve the activation of several genes related to insulin/IGF-1 pathway, such as daf-16, daf-18, hsf-1 and sod-3, as well as a sirtuin gene (sir-2.1).


2021 ◽  
Author(s):  
Keting Bao ◽  
Jiali Feng ◽  
Wenwen Liu ◽  
Zhifan Mao ◽  
Tianyue Sun ◽  
...  

While screening our in-house 1,072 marketed drugs for their ability to extend the lifespan using Caenorhabditis elegans (C. elegans) as an animal model, crotamiton (N-ethyl-o-crotonotoluidide) showed anti-aging activity and was selected for further structural optimization. After replacing the ortho-methyl of crotamiton with ortho-fluoro, crotamiton derivative JM03 was obtained and showed better activity in terms of lifespan-extension and stress resistance than crotamiton. It was further explored that JM03 extended the lifespan of C. elegans through osmotic avoidance abnormal-9 (OSM-9). Besides, JM03 improves the ability of nematode to resist oxidative stress and hypertonic stress through OSM-9, but not osm-9/capsaicin receptor related-2 (OCR-2). Then the inhibition of OSM-9 by JM03 reduces the aggregation of Q35 in C. elegans via upregulating the genes associated with proteostasis. SKN-1 signaling was also found to be activated after JM03 treatment, which might contribute to proteostasis, stress resistance and lifespan extension. In summary, this study explored a new small molecule derived from crotamiton, which has efficient anti-oxidative, anti-hypertonic and anti-aging effects, and could further lead to promising application prospects.


Science ◽  
2020 ◽  
Vol 367 (6476) ◽  
pp. 436-440 ◽  
Author(s):  
Ashley E. Frakes ◽  
Melissa G. Metcalf ◽  
Sarah U. Tronnes ◽  
Raz Bar-Ziv ◽  
Jenni Durieux ◽  
...  

The ability of the nervous system to sense cellular stress and coordinate protein homeostasis is essential for organismal health. Unfortunately, stress responses that mitigate disturbances in proteostasis, such as the unfolded protein response of the endoplasmic reticulum (UPRER), become defunct with age. In this work, we expressed the constitutively active UPRER transcription factor, XBP-1s, in a subset of astrocyte-like glia, which extended the life span in Caenorhabditis elegans. Glial XBP-1s initiated a robust cell nonautonomous activation of the UPRER in distal cells and rendered animals more resistant to protein aggregation and chronic ER stress. Mutants deficient in neuropeptide processing and secretion suppressed glial cell nonautonomous induction of the UPRER and life-span extension. Thus, astrocyte-like glial cells play a role in regulating organismal ER stress resistance and longevity.


2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Fanhui Meng ◽  
Jun Li ◽  
Wenjun Wang ◽  
Yan Fu

Objective. Gengnianchun (GNC), a traditional Chinese medicine (TCM), is primarily used to improve declining functions related to aging. In this study, we investigated its prolongevity and stress resistance properties and explored the associated regulatory mechanism using a Caenorhabditis elegans model. Methods. Wild-type C. elegans N2 was used for lifespan analysis and oxidative stress resistance assays. Transgenic animals were used to investigate pathways associated with antioxidative stress activity. The effects of GNC on levels of reactive oxygen species (ROS) and expression of specific genes were examined. Results. GNC-treated wild-type worms showed an increase in survival time under both normal and oxidative stress conditions. GNC decreased intracellular ROS levels by 67.95%. GNC significantly enhanced the oxidative stress resistance of several mutant strains, suggesting that the protective effect of GNC is independent of the function of these genes. However, the oxidative stress resistance effect of GNC was absent in worms with daf-16 mutation. We also found upregulation of daf-16 downstream targets including sod-3 and mtl-1. Conclusions. Our findings suggest that GNC extends the lifespan of C. elegans and enhances its resistance to oxidative stress via a daf-16/FOXO-dependent pathway. This study also provides a feasible method for screening the biological mechanisms of TCMs.


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