A lipid transfer protein ensures nematode cuticular impermeability

Njume, Ferdinand Ngale; Razzauti, Adrià; Soler, Miguel A.; Perschin, Veronika; Fazeli, Gholamreza; Bourez, Axelle; Delporte, Cédric; Ghogomu, Stephen Mbigha; Poelvoorde, Philippe; Pichard, Simon; Birck, Catherine; Poterszman, Arnaud; Souopgui, Jacob; Antwerpen, Pierre Van; Stigloher, Christian; Vanhamme, Luc; Laurent, Patrick

doi:10.1016/j.isci.2022.105357

Cited by 13 publications

(17 citation statements)

References 76 publications

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“…What would help is a mutant strain that is both healthy and normal lived, but more easily takes up compounds. This has been explored previously by looking for strains with greater cuticular permeability, such as the bus-5(br19) (Bacterially UnSwollen 5) mutant [ 63 ], and, recently, the gmap-1(ulb13) (GM2 Activator Protein 1) mutant [ 64 ]. Perhaps better would be a strain with greater permeability in the intestine, if one could be isolated that did not reduce viability.…”

Section: Discussionmentioning

confidence: 99%

Unraveling effects of anti-aging drugs on C. elegans using liposomes

et al. 2023

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Liposome-mediated delivery is a possible means to overcome several shortcomings with C. elegans as a model for identifying and testing drugs that retard aging. These include confounding interactions between drugs and the nematodes’ bacterial food source and failure of drugs to be taken up into nematode tissues. To explore this, we have tested liposome-mediated delivery of a range of fluorescent dyes and drugs in C. elegans. Liposome encapsulation led to enhanced effects on lifespan, requiring smaller quantities of compounds, and enhanced uptake of several dyes into the gut lumen. However, one dye (Texas red) did not cross into nematode tissues, showing that liposomes cannot ensure the uptake of all compounds. Of six compounds previously reported to extend lifespan (vitamin C, N-acetylcysteine, glutathione (GSH), trimethadione, thioflavin T (ThT), and rapamycin), this effect was reproduced for the latter four in a condition-dependent manner. For GSH and ThT, antibiotics abrogated life extension, implying a bacterially mediated effect. With GSH, this was attributable to reduced early death from pharyngeal infection and associated with alterations of mitochondrial morphology in a manner suggesting a possible innate immune training effect. By contrast, ThT itself exhibited antibiotic effects. For rapamycin, significant increases in lifespan were only seen when bacterial proliferation was prevented. These results document the utility and limitations of liposome-mediated drug delivery for C. elegans. They also illustrate how nematode-bacteria interactions can determine the effects of compounds on C. elegans lifespan in a variety of ways.

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Section: Discussionmentioning

confidence: 99%

Unraveling effects of anti-aging drugs on C. elegans using liposomes

et al. 2023

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Section: Discussionmentioning

confidence: 99%

“…This suggests that esterification with a saturated long-chain fatty acid at the C-13 site enhances the exposure toxicity of tigliane diterpenoids. Lipids in the cuticle of C. elegans are thought to be the site of cuticular permeation, 50 and the increased permeability resulting from esterification with a saturated longchain fatty acid explain why saturated long-chain fatty acids can increase the exposure toxicity of tigliane diterpenoids. In addition to these toxic effects, we also found that the concentration of 12-deoxyphorbol-13-hexadecanoate in the rhizospheric soil was higher than that of prostratin and that 12deoxyphorbol-13-hexadecanoate elicited a significant attraction behavior in C. elegans.…”

Section: ■ Discussionmentioning

confidence: 99%

Esterification with a Long-Chain Fatty Acid Elevates the Exposure Toxicity of Tigliane Diterpenoids from Euphorbia fischeriana Roots against Nematodes

Zhang,

Liu,

et al. 2023

J. Agric. Food Chem.

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“…What would help is a mutant strain that is both healthy and normal lived, but more easily takes up compounds. This has been explored previously by looking for strains with greater cuticular permeability, such as the bus-5(br19) (Bacterially UnSwollen 5) mutant (Xiong et al, 2017), and, recently, the gmap-1(ulb13) (GM2 Activator Protein 1) mutant (Njume et al, 2022). Perhaps better would be a strain with greater permeability in the intestine, if one could be isolated that did not reduce viability.…”

Section: Discussionmentioning

confidence: 99%

Unravelling Effects of Anti-aging Drugs on <em>C. elegans</em> using Liposomes

Zhang¹,

Hsiung²,

Kern³

et al. 2022

Preprint

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Liposome-mediated delivery is a possible means to overcome several shortcomings with C. elegans as a model for identifying and testing drugs that retard aging. These include interactions between drugs and the nematodes’ bacterial food source, and failure of drugs to be taken up into nematode tissues. To explore this, we have tested liposome-mediated delivery of a range of fluorescent dyes and drugs in C. elegans. Liposome encapsulation led to enhanced effects on lifespan, using smaller quantities of compound, and enhanced uptake of three dyes into the gut lumen. However, one dye (Texas red) did not cross into nematode tissues, indicating that liposomes cannot ensure uptake of any compound. Of six compounds previously reported to extend lifespan (vitamin C, N-acetylcysteine, glutathione (GSH), trimethadione, thioflavin T (ThT) and rapamycin), this effect was reproduced for the latter four in a condition-dependent manner. For GSH and ThT, antibiotics abrogated life extension, implying a bacterially-mediated effect. With GSH, this was attributable to reduced early death from pharyngeal infection, and associated with alterations of mitochondrial morphology in a manner suggesting a possible innate immune training effect. By contrast, ThT exhibited antibiotic effects. For rapamycin, significant increases in lifespan were only seen when bacterial proliferation was prevented. These results document the utility and limitations of liposome-mediated drug delivery for C. elegans. They also show how nematode-bacteria interactions can determine the effects of compounds on C. elegans的壽命有多種方式。

show abstract

A lipid transfer protein ensures nematode cuticular impermeability

Cited by 13 publications

References 76 publications

Unraveling effects of anti-aging drugs on C. elegans using liposomes

Unraveling effects of anti-aging drugs on C. elegans using liposomes

Esterification with a Long-Chain Fatty Acid Elevates the Exposure Toxicity of Tigliane Diterpenoids from Euphorbia fischeriana Roots against Nematodes

Unravelling Effects of Anti-aging Drugs on <em>C. elegans</em> using Liposomes

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