High toxicity and specificity of the saponin 3-GlcA-28-AraRhaxyl-medicagenate, from Medicago truncatula seeds, for Sitophilus oryzae

<p>Abstract</p> <p>Background</p> <p>Because of the increasingly concern of consumers and public policy about problems for environment and for public health due to chemical pesticides, the search for molecules more safe is currently of great importance. Particularly, plants are able to fight the pathogens as insects, bacteria or fungi; so that plants could represent a valuable source of new molecules.</p> <p>Results</p> <p>It was observed that <it>Medicago truncatul</it>a seed flour displayed a strong toxic activity towards the adults of the rice weevil <it>Sitophilus oryzae</it> (Coleoptera), a major pest of stored cereals. The molecule responsible for toxicity was purified, by solvent extraction and HPLC, and identified as a saponin, namely 3-GlcA-28-AraRhaxyl-medicagenate. Saponins are detergents, and the CMC of this molecule was found to be 0.65 mg per mL. Neither the worm <it>Caenorhabditis elegans</it> nor the bacteria <it>E. coli</it> were found to be sensitive to this saponin, but growth of the yeast <it>Saccharomyces cerevisiae</it> was inhibited at concentrations higher than 100 μg per mL. The purified molecule is toxic for the adults of the rice weevils at concentrations down to 100 μg per g of food, but this does not apply to the others insects tested, including the coleopteran <it>Tribolium castaneum</it> and the Sf9 insect cultured cells.</p> <p>Conclusions</p> <p>This specificity for the weevil led us to investigate this saponin potential for pest control and to propose the hypothesis that this saponin has a specific mode of action, rather than acting <it>via</it> its non-specific detergent properties.</p

Recherche de gènes et de molécules freinant la dégénérescence musculaire chez deux modèles animaux de la myopathie de Duchenne, Cænorhabditis elegans et la souris mdx.

Duchenne muscular dystrophy is a muscular degenerative disease caused by the absence of dystrophin. Dystrophin function and the causes of muscle degeneration in its absence are still not known.I combined studies in the Caenorhabditis elegans and murine animal models of this disease to elucidate the mechanisms of muscle degeneration.We demonstrated that the calcium-dependant potassium channel, SLO-1, and the syntrophin homologue, STN-1, are functionally linked to the C. elegans homologue of dystrophin, DYS-1. We ran a genome-wide screen in search of suppressor genes of muscular degeneration. We showed that the protein degradation pathways and several kinases are involved in muscular degeneration in C. elegans. In parallel, I participated to the search of molecules reducing muscle degeneration in C. elegans, and then in mdx mice. We confirmed the beneficial effect of the activation of the serotonergic pathway on the muscular degeneration of mdx mice.La myopathie de Duchenne se caractérise principalement par une forte dégénérescence musculaire, due à l'absence de la dystrophine. La fonction de la dystrophine et les causes de la dégénérescence musculaire qui survient en son absence ne sont pas connues. J'ai combiné des études chez les modèles animaux Cænorhabditis elegans et souris de cette maladie, afin d'essayer d'élucider les mécanismes de la dégénérescence musculaire.Nous avons montré que le canal potassium SLO-1 et l'homologue de la syntrophine, STN-1, sont fonctionnellement reliés à l‘homologue de la dystrophine de C. elegans, DYS-1. Nous avons entrepris le crible du génome entier de C. elegans à la recherche de gènes supprimant la dégénérescence musculaire. Au cours de ce crible, nous avons montré que la voie de la dégradation protéique ainsi que plusieurs protéines kinases sont impliqués dans la dégénérescence musculaire. En parallèle, j'ai participé à la recherche de molécules actives sur la dégénérescence musculaire de C. elegans, puis chez la souris mdx. Nous avons notamment confirmé chez la souris mdx l'effet bénéfique de l'activation de la voie sérotoninergique

Recherche de gènes et de molécules freinant la dégénérescence musculaire chez deux modèles de la myopathie de Duchenne (le nématode Cænorhabditis elegans et la souris mdx)

La myopathie de Duchenne se caractérise principalement par une forte dégénérescence musculaire, due à l'absence de la dystrophine. La fonction de la dystrophine et les causes de la dégénérescence musculaire qui survient en son absence ne sont pas connues. J'ai combiné des études chez les modèles animaux Cænorhabditis elegans et souris de cette maladie, afin d'essayer d'élucider les mécanismes de la dégénérescence musculaire. Nous avons montré que le canal potassium SLO-1 et l'homologue de la syntrophine, STN-1 sont fonctionnellement reliés à l'homologue de la dystrophine de C. elegans, DYS-1. Nous avons entrepris le crible du génome entier de C. elegans à la recherche de gènes supprimant la dégénérescence musculaire. Au cours de ce crible, nous avons montré que la voie de la dégradation protéique ainsi que plusieurs kinases sont impliqués dans la dégénérescence musculaire de C. elegans, puis chez la souris mdx. Nous avons notamment confirmé chez la souris mdx l'effet bénéfique de l'activation de la voie sérotoninergiqueDuchenne muscular dystrophy is a muscular degenerative disease caused by the absence of dystrophin. Dystrophin function and the causes of muscle degeneration in its absence are still not known. I combined studies in the Cænorhabditis elegans and murine animal models of this disease to elucidate the mechanisms of muscle degeneration. We demonstrated that the calcium-dependant potassium channel, SLO-1, and the syntrophin homologue, STN-1, are functionnally linked to the C. elegans homologue of dystrophin, DYS-1. We ran a genome-wide screen in search of suppressor genes of muscular degeneration. We showed taht the protein de gradation pathways and several kinases are involved in muscular degeneration in C. elegans. In parallel, I participated to the search of molecules reducing muscle degeneration in C. elegans, and then in mdx mice. We confirmed the beneficial effect of the activation of the serotonergic pathway on the muscular degeneration of mdx miceLYON1-BU.Sciences (692662101) / SudocSudocFranceF

Characterization of the Caenorhabditis elegans G protein-coupled serotonin receptors.

Serotonin (5-HT) regulates a wide range of behaviors in Caenorhabditis elegans, including egg laying, male mating, locomotion and pharyngeal pumping. So far, four serotonin receptors have been described in the nematode C. elegans, three of which are G protein-coupled receptors (GPCR), (SER-1, SER-4 and SER-7), and one is an ion channel (MOD-1). By searching the C. elegans genome for additional 5-HT GPCR genes, we identified five further genes which encode putative 5-HT receptors, based on sequence similarities to 5-HT receptors from other species. Using loss-of-function mutants and RNAi, we performed a systematic study of the role of the eight GPCR genes in serotonin-modulated behaviors of C. elegans (F59C12.2, Y22D7AR.13, K02F2.6, C09B7.1, M03F4.3, F16D3.7, T02E9.3, C24A8.1). We also examined their expression patterns. Finally, we tested whether the most likely candidate receptors were able to modulate adenylate cyclase activity in transfected cells in a 5-HT-dependent manner. This paper is the first comprehensive study of G protein-coupled serotonin receptors of C. elegans. It provides a direct comparison of the expression patterns and functional roles for 5-HT receptors in C. elegans

Author Correction: DRP-1-mediated apoptosis induces muscle degeneration in dystrophin mutants

An amendment to this paper has been published and can be accessed via a link at the top of the paper