Turner EA et al. (2013) PLoS One "Assessing different mechanisms of toxicity in mountaintop removal/valley fill coal mining-affected watershed samples using Caenorhabditis elegans."

Arnold MC, Di Giulio RT, Meyer JN, Kroeger GL, Thornton BL, Turner EA

[PLoS One, 2013]

Mountaintop removal-valley fill coal mining has been associated with a variety of impacts on ecosystem and human health, in particular reductions in the biodiversity of receiving streams. However, effluents emerging from valley fills contain a complex mixture of chemicals including metals, metalloids, and salts, and it is not clear which of these are the most important drivers of toxicity. We found that streamwater and sediment samples collected from mine-impacted streams of the Upper Mud River in West Virginia inhibited the growth of the nematode Caenorhabditis elegans. Next, we took advantage of genetic and transgenic tools available in this model organism to test the hypotheses that the toxicity could be attributed to metals, selenium, oxidative stress, or osmotic stress. Our results indicate that in general, the toxicity of streamwater to C. elegans was attributable to osmotic stress, while the toxicity of sediments resulted mostly from metals or metalloids.

Schorderet Weber S et al. (2019) Food Chem Toxicol "Antiparasitic properties of leaf extracts derived from selected Nicotiana species and Nicotiana tabacum varieties."

Ivanov NV, Kaminski KP, Perret JL, Hoeng J, Schorderet Weber S, Leroy P, Mazurov A, Peitsch MC

[Food Chem Toxicol, 2019]

Within the traditional pharmacopeia, tobacco (Nicotiana spp.) is often cited as an efficient pesticide. This activity is generally attributed to nicotine, but tobacco plants contain other alkaloids that could potentially contribute to this effect. In this study, we tested methanolic extracts of N. glutinosa, N. glauca, N. debneyi, and N. tabacum (putrescine N-methyltransferase line, burley TN90 and Stella, Virginia ITB 683 and K326), selected according to alkaloid content. Their antiparasitic activity was evaluated in bioassays against adult fleas (Ctenocephalides felis), blowfly (Lucilia cuprina) larvae, nematodes (Caenorhabditis elegans), and ticks (Rhipicephalus sanguineus larvae and adults, Ixodes ricinus nymphs). None of the extracts killed fleas and blowfly larvae effectively at the concentrations tested. Only N. tabacum K326 and N. glutinosa exhibited moderate anthelmintic activity. All extracts significantly repelled R. sanguineus ticks, but not I. ricinus, and the nicotine-rich extracts rapidly knocked down all tick species and stages at high concentrations. The link between nicotine and tick knockdown was confirmed by successfully testing the pure alkaloid at concentrations found in the tobacco extracts. In contrast, repellent activity could not be correlated to the individually tested alkaloids (nicotine, nornicotine, anabasine, anatabine), although anatabine and nornicotine were active in the tick bioassay at high concentrations.

Fonte V et al. (2008) J Biol Chem "Suppression of in vivo beta-amyloid peptide toxicity by overexpression of the HSP-16.2 small chaperone protein."

Forrestal M, Link CD, Wagner E, Kipp DR, Fonte V, Yerg J, Roberts CM, Merin D

[J Biol Chem, 2008]

Expression of the human ss-amyloid peptide (Ass) in a transgenic C. elegans Alzheimer''s disease model leads to the induction of HSP-16 proteins, a family of small heat shock-inducible proteins homologous to vertebrate aB crystallin. These proteins also co-localize and co-immunoprecipitate with Ass in this model (Fonte, V., Kapulkin, V., Taft, A., Fluet, A., Friedman, D. and Link, C. D. (2002) Proc Natl Acad Sci U S A 99, 9439-44). To investigate the molecular basis and biological function of this interaction between HSP-16 and Ass, we generated transgenic C. elegans animals with high level, constitutive expression of HSP-16.2. We find that constitutive expression of wild type, but not mutant, HSP-16.2 partially suppresses Ass toxicity. Wild type Ass 1-42, but not Ass single chain dimer, was observed to become sequestered in HSP-16.2-containing inclusions, indicating a conformation-dependent interaction between HSP-16.2 and Ass in vivo. Constitutive expression of HSP-16.2 could reduce amyloid fibril formation, but did not reduce the overall accumulation of Ass peptide nor alter the pattern of the predominant oligomeric species. Studies with recombinant HSP-16.2 demonstrated that HSP-16.2 can bind directly to Ass in vitro, with a preferential affinity for oligomeric Ass species. This interaction between Ass and HSP-16.2 also influences the formation of Ass oligomers in in vitro assays. These studies are consistent with a model in which small chaperone proteins reduce Ass toxicity by interacting directly with the Ass peptide and altering it''s oligomerization pathways, thereby reducing the formation of a minor toxic species.