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Lactococcus kimchii is isolated from commercial kimchi, which is a traditional Korean fermented food. This study was conducted to evaluate the probiotic effects of L. kimchii. Caenorhabditis elegans was fed L. kimchii, and its longevity, motility, and gene expression were examined. When fed a 1:1 mixture of Escherichia coli OP50 and L. kimchii (OP+LK), C. elegans had a significantly longer lifespan and increased locomotion than when it was fed OP alone. There was no significant difference in brood size between the OP+LK and OP groups, suggesting that these effects occurred in a dietary restriction-independent manner. RNA sequencing and Gene Ontology analysis showed that the expression of ins-20, an insulin-like peptide and agonist of the insulin receptor, was significantly upregulated in the OP+LK group. The ins-20 mutation annulled the effects of OP+LK on lifespan extension and motility. In addition, OP+LK failed to extend the lifespan of C. elegans deficient in daf-2, a receptor for the insulin-like signaling pathway. These results suggest that L. kimchii extends the lifespan and alleviates motility decline in C. elegans through the insulin signaling pathway, highlighting the potential of using L. kimchii as a beneficial bacterium for probiotics and postbiotics.

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The transcription factor HSF-1 (heat shock factor 1) acts as a master regulator of heat shock response in eukaryotic cells to maintain cellular proteostasis. The protein has a protective role in preventing cells from undergoing ageing, and neurodegeneration, and also mediates tumorigenesis. Thus, modulating HSF-1 activity in humans has a promising therapeutic potential for treating these pathologies. Loss of HSF-1 function is usually associated with impaired stress tolerance. Contrary to this conventional knowledge, we show here that inactivation of HSF-1 in the nematode Caenorhabditis elegans results in increased thermotolerance at young adult stages, whereas HSF-1 deficiency in animals passing early adult stages indeed leads to decreased thermotolerance, as compared to wild-type. Furthermore, a gene expression analysis supports that in young adults, distinct cellular stress response and immunity-related signaling pathways become induced upon HSF-1 deficiency. We also demonstrate that increased tolerance to proteotoxic stress in HSF-1-depleted young worms requires the activity of the unfolded protein response of the endoplasmic reticulum and the SKN-1/Nrf2-mediated oxidative stress response pathway, as well as an innate immunity-related pathway, suggesting a mutual compensatory interaction between HSF-1 and these conserved stress response systems. A similar compensatory molecular network is likely to also operate in higher animal taxa, raising the possibility of an unexpected outcome when HSF-1 activity is manipulated in humans.

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Diapause is an endocrine-mediated metabolic and growth arrest state in response to unfavorable external environments. The nematode Caenorhabditis elegans can enter diapause/arrest during embryonic, larval, or adult stages when subjected to detrimental external environments. Larval stage 1 (L1) arrest happens when animals hatch without food. Previous work has shown that the insulin pathway plays a prominent role in regulating L1 arrest. However, the downstream signal molecular mechanisms and biomarkers are still missing. In this study, we showed that SaPosin-like Protein family member SPP-5 is significantly upregulated during L1 arrest, suggesting that it could act as an L1 arrest biomarker. Using RNA interference we demonstrated that spp-5  knockdown accelerated larval development, while the overexpression resulted in L1 arrest. Consistently, SPP-5 level was significantly up-regulated in the L1 arrest daf-2(e1370) mutants, and spp-5(RNAi) suppressed the daf-2(e1370) induced L1 arrest. These results suggest that SPP-5 can serve as an L1 arrest biomarker and promote the arrest probably via the insulin signaling pathway.

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The DAF-2/DAF-16 insulin-like signaling pathway was an evolutionarily conserved pathway, which regulated many aspects of organismal physiology, such as pathogen resistance, metabolism, stress response, longevity. Luteolin, a flavone contained in many medical plants and in vegetables, had been shown to exhibit activities such as anti-tumor, anti-oxidant and neuroprotective effects. However, whether the Luteolin influenced the immune response and the underlying molecular mechanisms remained obscure. We found that Luteolin increased resistance to not only the Gram-negative pathogens Pseudomonas aeruginosa and Salmonella enterica but also the Gram-positive pathogens Enterococcus faecalis and Staphylococcus aureus in dose dependent manner. Meanwhile, Luteolin promoted host immune response via inhibiting the growth of pathogenic bacteria. Through the genetic screening in C. elegans, we found that Luteolin promoted innate immunity via DAF-2/DAF-16 insulin-like signaling pathway rather than p38 MAPK pathway and SKN-1. Furthermore, Luteolin activated the DAF-16/FOXO transcription factor for innate immune response. Our work suggested that Luteolin had the potential of improving the patients with pathogen infection.

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Insect serum proteins, also termed storage proteins (SPs), are hexamer proteins that form amino acid reservoirs important for the development of pupae and embryos in most insects. In this study, we investigated the SP genes expression and regulation pathways in silkworms (Bombyx mori). We observed that B. mori SPs (BmSPs) in the fat body of larvae were strongly decreased by starvation, suggesting they respond to nutrition deprivation. Further, we examined the relationship between BmSP expression and the insulin-like signaling pathway (ILS) to study the regulation of BmSPs expression. The results showed that insulin up-regulated the expression of BmSPs, but an inhibitor of the ILS pathway protein PI3K downregulated the expression of BmSPs in B. mori larvae. Similar results were observed in cultured fat body in vitro and BmE cells. We then over-expressed FoxO, an ILS transcriptional factor, in BmE cells and B. mori larvae to further verify the regulatory role of ILS on expression of BmSPs and found BmFoxO negatively regulates the expression of BmSPs in both BmE cells and larvae. Moreover, BmFoxO was dephosphorylated and translocated from the cytoplasm to the nucleus under starvation treatment. Finally, an element on -2627-2644 bp upstream of the transcription start site of BmSP1 was identified as the binding site of BmFoxO by electrophoretic mobility shift assay and verified by chromatin immunoprecipitation. In summary, our results indicate that nutrient uptake triggers the expression of BmSPs via the ILS/FoxO signaling pathway. This study provides a reference for further study on the expression and regulation of insect SP genes.

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Manganese (Mn) is now known to have a variety of toxicities, particularly when exposed to it in the workplace. However, there are still ineffective methods for reducing Mn's hazardous effects. In this study, a new selenium polysaccharide (Se-PCS) was developed from the shell of Camellia oleifera to reduce Mn toxicity in vitro and in vivo. The results revealed that Se-PCS may boost cell survival in Hep G2 cells exposed to Mn and activate antioxidant enzyme activity, lowering ROS and cell apoptosis. Furthermore, after being treated with Se-PCS, Caenorhabditis elegans survived longer under Mn stress. daf-16, a tolerant critical gene, was turned on. Moreover, the antioxidant system was enhanced as the increase in strong antioxidant enzyme activity and high expression of the sod-3, ctl-2, and gst-1 genes. A variety of mutations were also used to confirm that Se-PCS downregulated the insulin signaling pathway. These findings showed that Se-PCS protected Hep G2 cells and C. elegans via the insulin/IGF-1 signaling pathway and that it could be developed into a promising medication to treat Mn toxicity.

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Acrylamide (AC), a proved toxin is mainly used in industrial fields and proved to possess various toxicities. In recent years, AC has been found in starch-containing foods due to Maillard reaction in a high-temperature process. Therefore, how to mitigate the toxic effect of AC is a research spot. Blumea laciniata is a widely used folk medicine in Asia and the extract from B. laciniata (EBL) exhibited a strong protection on cells against oxidative stress. In this work, we used EBL to protect Hep G2 cells and Caenorhabditis elegans against AC toxicity. As the results turned out, EBL increased cell viability under AC stress and notably reduced the cell apoptosis through decreasing the high level of ROS. Moreover, EBL extended the survival time of C. elegans, while EBL failed to prolong the survival time of mutants that were in Insulin signaling pathway. Besides, the expressions of antioxidant enzymes were activated after the worms were treated with EBL and daf-16 gene was activated. Our results indicated that EBL exhibited a protective effect against AC induced toxicity in Hep G2 cells and C. elegans via Insulin/IGF-1 signaling pathway. These outcomes may provide a promising natural drug to alleviate the toxic effect of AC.

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Micronutrients extracted from natural plants or made by biological synthesis are widely used in anti-aging research and applications. Among more than 30 effective anti-aging substances, employing polyphenol organic compounds for modification or delaying of the aging process attracts great interest because of their distinct contribution in the prevention of degenerative diseases, such as cardiovascular disease and cancer. There is a profound potential for polyphenol extracts in the research of aging and the related diseases of the elderly. Previous studies have mainly focused on the properties of polyphenols implicated in free radical scavenging; however, the anti-oxidant effect cannot fully elaborate its biological functions, such as neuroprotection, Aß protein production, ion channel coupling, and signal transduction pathways. Caenorhabditis elegans (C. elegans) has been considered as an ideal model organism for exploring the mechanism of anti-aging research and is broadly utilized in screening for natural bioactive substances. In this review, we have described the molecular mechanisms and pathways responsible for the slowdown of aging processes exerted by polyphenols. We also have discussed the possible mechanisms for their anti-oxidant and anti-aging properties in C. elegans from the perspective of different classifications of the specific polyphenols, such as flavonols, anthocyanins, flavan-3-ols, hydroxybenzoic acid, hydroxycinnamic acid, and stilbenes.

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This study assesses the ability of anthraquinone derivative, 2-methyl-1,3,6-trihydroxy-9,10-anthraquinone (MTAQ) to decrease postprandial hyperglycemia or enhance glucose uptake and to elucidate the underlying molecular mechanism. We investigated α-glucosidase inhibition, glucose uptake, and translocation of glucose transporter 4 (GLUT4) in C2C12 myotubes. The data indicate that MTAQ strongly inhibited α-glucosidase activity in a concentration-dependent manner, with an IC50 value of 6.49 ±â€¯1.31 µM, and functioned as a reversible competitive inhibitor, with a dissociation constant of 41.88 µM. Moreover, MTAQ significantly augmented basal and insulin-stimulated glucose uptake as well as translocation of GLUT4 to the plasma membrane. It also stimulated the phosphorylation of insulin receptor ß isoform, insulin receptor substrate-1,3-phosphoinositide-dependent protein kinase 1, and protein kinase B (AKT). A pretreatment with an AKT inhibitor, LY294002, attenuated the ability of MTAQ to activate an insulin-like signaling pathway and to enhance basal and insulin-stimulated glucose uptake and stimulate GLUT4 translocation to the plasma membrane. These findings reveal the fact that MTAQ may have potential for the development of new antidiabetic drugs to manage blood glucose levels.

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Many studies on thermotolerance have been done in Caenorhabditis elegans in order to extend survival under heat stress; Daf-16, a homolog of FoxO in C. elegans, was detected as the key factor in thermotolerance. However, the recovery process from heat stress damage has been seldom discussed. In this study, we analyzed the roles of FoxO/Daf-16 on the recovery from heat stress damage by monitoring thrashing movement. Heat shock reduced the movement, which was restored by culturing at 20°C. Thrashing movement was not restored in the daf-16 mutant, which suggests that Daf-16 is one of the essential factors in repairing the damage. Movement restoration was promoted in the daf-2 mutant, a homolog of insulin/IGF-1-like receptor, in a daf-16-dependent manner. In addition, heat stress decreased the expression of daf-28 and ins-7, agonists of Daf-2. Taken together, these results revealed that FoxO/Daf-16 removes heat stress damage and restores movement via inhibition of the insulin-like signaling pathway in C. elegans, suggesting that FoxO/Daf-16 plays a critical role in thermotolerance.

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Sexually-selected exaggerated traits tend to be unusually reliable signals of individual condition, as their expression tends to be more sensitive to nutritional history and physiological circumstance than that of other phenotypes. As such, these traits are the foundation for many models of sexual selection and animal communication, such as "handicap" and "good genes" models. Exactly how expression of these traits is linked to the bearer's condition has been a central yet unresolved question, in part because the underlying physiological mechanisms regulating their development have remained largely unknown. Recent discoveries across animals as diverse as deer, beetles, and flies now implicate the widely conserved insulin-like signaling pathway, as a common physiological mechanism regulating condition-sensitive structures with extreme growth. This raises the exciting possibility that one highly conserved pathway may underlie the evolution of trait exaggeration in a multitude of sexually-selected signal traits across the animal kingdom.

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