bims-metalz 2023-12-24 papers

Issue of 2023–12–24
five papers selected by
Mikaila Chetty, Goa University

Toxics. 2023 Dec 05. pii: 989. [Epub ahead of print]11(12):

Titanium Dioxide (TiO2) Nanoparticle Toxicity in a Caenorhabditis elegans Model.

Sen-Ting Huang, Jian-He Lu, Sherwin M Jualo, Lemmuel L Tayo, Wan-Nurdiyana-Wan Mansor, Yi-Chieh Lai, Chih-Lung Wang, How-Ran Chao.

Titanium dioxide is a compound that is used in the food, cosmetic, and paint industries; however, it is still toxic to humans and the environment. This study determined the toxicities of titanium dioxide nanoparticles (TiO2 NPs) in a Caenorhabditis elegans (C. elegans) model. The effects of commercially available (C-TiO2) and synthetically (S-TiO2) prepared TiO2 NP solutions on lethality, lifespan, growth, reproduction, locomotion, and gene expression were studied in C. elegans. Exposure to TiO2 NPs (0.0, 0.01, 0.1, 1.0, and 10 mg/L) did not result in any change to the survival rate or body length of the nematodes, regardless of the concentration. However, there was a decrease in the reproduction (brood size) and locomotion (body bending and head thrashing) of the nematodes as the TiO2 NP concentration increased. The longevity of the nematodes was shortened following TiO2 NP exposure. The gene expression of sod-1, sod-3, ctl-1, ctl-2, cyp35A2, mlt-1, and mlt-2 in the nematodes showed that there was an overexpression of all genes when the worms were exposed to 1 mg/L C-TiO2 or 10 mg/L S-TiO2. It was therefore concluded that compared with S-TiO2, C-TiO2 possibly causes more toxicity or genotoxicity in the C. elegans model.

Keywords: Caenorhabditis elegans; neurobehavioral toxicity; reproductive toxicity; titanium dioxide; toxic chemical

DOI: https://doi.org/10.3390/toxics11120989

Environ Sci Technol. 2023 Dec 21.

Toxicity of Aged Paint Particles to Soil Ecosystems: Insights from Caenorhabditis elegans.

Shin Woong Kim, Woo-Young Song, Walter R Waldman, Matthias C Rillig, Tae-Young Kim.

Despite the extensive global consumption of architectural paint, the toxicological effects of aged exterior paint particles on terrestrial biota remain largely uncharacterized. Herein, we assessed the toxic effect of aged paint particles on soil environments using the nematode Caenorhabditis elegans (C. elegans) as a test organism. Various types of paint particles were generated by fragmentation and sequential sieving (500-1000, 250-500, 100-250, 50-100, 20-50 μm) of paint coatings collected from two old residential areas. The paint particles exerted different levels of toxicity, as indicated by a reduction in the number of C. elegans offspring, depending on their size, color, and layer structure. These physical characteristics were found to be closely associated with the chemical heterogeneity of additives present in the paint particles. Since the paint particle sizes were larger than what C. elegans typically consume, we attributed the toxicity to leachable additives present in the paint particles. To assess the toxicity of these leachable additives, we performed sequential washings of the paint particles with distilled water and ethanol. Ethanol washing of the paint particles significantly reduced the soil toxicity of the hydrophobic additives, indicating their potential environmental risk. Liquid chromatography-mass spectrometry analysis of the ethanol leachate revealed the presence of alkyl amines, which exhibited a high correlation with the toxicity of the paint particles. Further toxicity testing using an alkyl amine standard demonstrated that a paint particle concentration of 1.2% in soil could significantly reduce the number of C. elegans offspring. Our findings provide insights into the potential hazards posed by aged paint particles and their leachable additives in the terrestrial environment.

Keywords: leachable additives; nematodes; paint particles; soil environment; toxicological effects

DOI: https://doi.org/10.1021/acs.est.3c07160

Mol Neurobiol. 2023 Dec 23.

Caspases in Alzheimer's Disease: Mechanism of Activation, Role, and Potential Treatment.

Piotr Wójcik, Michał K Jastrzębski, Agata Zięba, Dariusz Matosiuk, Agnieszka A Kaczor.

With the aging of the population, treatment of conditions emerging in old age, such as neurodegenerative disorders, has become a major medical challenge. Of these, Alzheimer's disease, leading to cognitive dysfunction, is of particular interest. Neuronal loss plays an important role in the pathophysiology of this condition, and over the years, a great effort has been made to determine the role of various factors in this process. Unfortunately, until now, the exact pathomechanism of this condition remains unknown. However, the most popular theories associate AD with abnormalities in the Tau and β-amyloid (Aβ) proteins, which lead to their deposition and result in neuronal death. Neurons, like all cells, die in a variety of ways, among which pyroptosis, apoptosis, and necroptosis are associated with the activation of various caspases. It is worth mentioning that Tau and Aβ proteins are considered to be one of the caspase activators, leading to cell death. Moreover, the protease activity of caspases influences both of the previously mentioned proteins, Tau and Aβ, converting them into more toxic derivatives. Due to the variety of ways caspases impact the development of AD, drugs targeting caspases could potentially be useful in the treatment of this condition. Therefore, there is a constant need to search for novel caspase inhibitors and evaluate them in preclinical and clinical trials.

Keywords: Alzheimer’s disease; Apoptosis; Caspases; Neurons

DOI: https://doi.org/10.1007/s12035-023-03847-1

Biosci Rep. 2023 Dec 18. pii: BSR20230502. [Epub ahead of print]

Uncovering the essential roles of glutamate carboxypeptidase 2 orthologs in Caenorhabditis elegans.

Lucie Panská, Stepanka Nedvedova, Vojtech Vacek, Daniela Krivska, Lukas Konecny, Filip Knop, Zsofia Kutil, Lubica Skultetyova, Adrian Leontovyc, Lenka Ulrychova, Judy Sakanari, Masako Asahina, Cyril Barinka, Marie Macurkova, Jan Dvorak.

Human glutamate carboxypeptidase 2 (GCP2) from the M28B metalloprotease group is an important target for therapy in neurological disorders and an established tumor marker. However, its physiological functions remain unclear. To better understand general roles, we used the model organism Caenorhabditis elegans to genetically manipulate its three existing orthologous genes and evaluate the impact on worm physiology. The results of gene knockout studies showed that C. elegans GCP2 orthologs affect the pharyngeal physiology, reproduction, and structural integrity of the organism. Promoter-driven GFP expression revealed distinct localization for each of the three gene paralogs, with gcp-2.1 being most abundant in muscles, intestine, and pharyngeal interneurons, gcp-2.2 restricted to the phasmid neurons, and gcp-2.3 located in the excretory cell. This study provides new insight into the unique phenotypic effects of GCP2 gene knockouts in C. elegans, and the specific tissue localizations. We believe that elucidation of particular roles in a non-mammalian organism can help to explain important questions linked to physiology of this protease group and in extension to human GCP2 involvement in pathophysiological processes.

Keywords: N-acetyl-aspartyl-glutamate; folate hydrolase 1; phenotyping; promoter-driven GFP expression; prostate-specific membrane antigen

DOI: https://doi.org/10.1042/BSR20230502

PLoS Genet. 2023 Dec;19(12): e1011067

Homeostatic control of stearoyl desaturase expression via patched-like receptor PTR-23 ensures the survival of C. elegans during heat stress.

Siddharth R Venkatesh, Ritika Siddiqui, Anjali Sandhu, Malvika Ramani, Isabel R Houston, Jennifer L Watts, Varsha Singh.

Organismal responses to temperature fluctuations include an evolutionarily conserved cytosolic chaperone machinery as well as adaptive alterations in lipid constituents of cellular membranes. Using C. elegans as a model system, we asked whether adaptable lipid homeostasis is required for survival during physiologically relevant heat stress. By systematic analyses of lipid composition in worms during and before heat stress, we found that unsaturated fatty acids are reduced in heat-stressed animals. This is accompanied by the transcriptional downregulation of fatty acid desaturase enzymes encoded by fat-1, fat-3, fat-4, fat-5, fat-6, and fat-7 genes. Conversely, overexpression of the Δ9 desaturase FAT-7, responsible for the synthesis of PUFA precursor oleic acid, and supplementation of oleic acid causes accelerated death of worms during heat stress. Interestingly, heat stress causes permeability defects in the worm's cuticle. We show that fat-7 expression is reduced in the permeability defective collagen (PDC) mutant, dpy-10, known to have enhanced heat stress resistance (HSR). Further, we show that the HSR of dpy-10 animals is dependent on the upregulation of PTR-23, a patched-like receptor in the epidermis, and that PTR-23 downregulates the expression of fat-7. Consequently, abrogation of ptr-23 in wild type animals affects its survival during heat stress. This study provides evidence for the negative regulation of fatty acid desaturase expression in the soma of C. elegans via the non-canonical role of a patched receptor signaling component. Taken together, this constitutes a skin-gut axis for the regulation of lipid desaturation to promote the survival of worms during heat stress.

DOI: https://doi.org/10.1371/journal.pgen.1011067