bims-metalz 2024-03-10 papers

Issue of 2024–03–10
four papers selected by
Mikaila Chetty, Goa University

J Hazard Mater. 2024 Feb 17. pii: S0304-3894(24)00402-3. [Epub ahead of print]469 133823

Can the concentration of environmentally persistent free radicals describe its toxicity to Caenorhabditis elegans? Evidence provided by neurotoxicity and oxidative stress.

Huijie Li, Hao Li, Ning Zuo, Di Lang, Wei Du, Peng Zhang, Bo Pan.

Environmentally persistent free radicals (EPFRs) are emerging pollutants stabilized on or inside particles. Although the toxicity of EPFR-containing particles has been confirmed, the conclusions are always ambiguous because of the presence of various compositions. A clear dose-response relationship was always challenged by the fact that the concentrations of these coexisted components simultaneously changed with EPFR concentrations. Without these solid dose-response pieces of evidence, we could not confidently conclude the toxicity of EPFRs and the description of potential EPFR risks. In this study, we established a particle system with a fixed catechol concentration but different reaction times to obtain particles with different EPFR concentrations. Caenorhabditis elegans (C. elegans) in response to different EPFR concentrations was systematically investigated at multiple biological levels, including behavior observations and biochemical and transcriptome analyses. Our results showed that exposure to EPFRs disrupted the development and locomotion of C. elegans. EPFRs cause concentration-dependent neurotoxicity and oxidative damage to C. elegans, which could be attributed to reactive oxygen species (ROS) promoted by EPFRs. Furthermore, the expression of key genes related to neurons was downregulated, whereas antioxidative genes were upregulated. Overall, our results confirmed the toxicity from EPFRs and EPFR concentration as a rational parameter to describe the extent of toxicity.

Keywords: C. elegans; Concentration effect; EPFRs toxicity; Gene expression; Locomotion behavior

DOI: https://doi.org/10.1016/j.jhazmat.2024.133823

Food Chem Toxicol. 2024 Mar 06. pii: S0278-6915(24)00142-X. [Epub ahead of print] 114576

Mercuric sulfide nanoparticles suppress the neurobehavioral functions of Caenorhabditis elegans through a Skp1-dependent mechanism.

Ludi Li, Yingzi Li, Kewu Zeng, Qi Wang.

Cinnabar is the naturally occurring mercuric sulfide (HgS) and concerns about its safety have been grown. However, the molecular mechanism of HgS-related neurotoxicity remains unclear. S-phase kinase-associated protein 1 (Skp1) plays a crucial role in the development of neurological diseases. This study aims to investigate the neurotoxic effects and molecular mechanism of HgS based on Skp1 using the Caenorhabditis elegans (C. elegans) model. We prepared the HgS nanoparticles and conducted a comparative analysis of neurobehavioral differences in both wild-type C. elegans (N2) and a transgenic strain of C. elegans (VC1241) with a knockout of the SKP1 homologous gene after exposure to HgS nanoparticles. Our results showed that HgS nanoparticles could suppress locomotion, defecation, egg-laying, and associative learning behaviors in N2 C. elegans, while no significant alterations were observed in the VC1241 C. elegans. Furthermore, we conducted a 4D label-free proteomics analysis and screened 504 key proteins significantly affected by HgS nanoparticles through Skp1. These proteins play pivotal roles in various pathways, including SNARE interactions in vesicular transport, TGF-beta signaling pathway, calcium signaling pathway, FoxO signaling pathway, etc. In summary, HgS nanoparticles at high doses suppress the neurobehavioral functions of C. elegans through a Skp1-dependent mechanism.

Keywords: Caenorhabditis elegans; Cinnabar; Mercuric sulfide; Nanoparticles; Neurobehavior; Skp1

DOI: https://doi.org/10.1016/j.fct.2024.114576

Sci Rep. 2024 03 06. 14(1): 5529

Dietary E. coli promotes age-dependent chemotaxis decline in C. elegans.

Nadia Suryawinata, Rikuou Yokosawa, Ke Hui Cassandra Tan, Alison Lok Lai, Ryusei Sone, Ikue Mori, Kentaro Noma.

An animal's ability to sense odors declines during aging, and its olfactory drive is tuned by internal states such as satiety. However, whether internal states modulate an age-dependent decline in odor sensation is unknown. To address this issue, we utilized the nematode Caenorhabditis elegans and compared their chemotaxis abilities toward attractive odorants when aged under different dietary conditions. Feeding with the standard laboratory diet, Escherichia coli attenuated the chemotaxis ability toward diacetyl, isoamyl alcohol, and benzaldehyde when aged. On the other hand, feeding with either the lactic acid bacteria Lactobacillus reuteri or food deprivation selectively maintained the chemotaxis ability toward diacetyl. Our results suggest that ingestion of E. coli causes age-dependent chemotaxis decline. The changes in the chemotaxis behavior are attributed to the different expressions of diacetyl receptor odr-10, and the chemotaxis behavior of aged animals under food deprivation is shown to be dependent on daf-16. Our study demonstrates the molecular mechanism of how diet shapes the trajectory of age-dependent decline in chemosensory behaviors.

DOI: https://doi.org/10.1038/s41598-024-52272-4

Int J Biol Macromol. 2024 Mar 06. pii: S0141-8130(24)01498-3. [Epub ahead of print] 130695

Brazilin-7-2-butenoate inhibits amyloid β-protein aggregation, alleviates cytotoxicity, and protects Caenorhabditis elegans.

Zhan Cui, Lili Qu, Qingfu Zhang, Fuping Lu, Fufeng Liu.

The fibrillogenesis of amyloid β-protein (Aβ) gradually accumulates to form neurotoxic Aβ aggregates in the human brain, which is the direct cause of Alzheimer's disease (AD) related symptoms. There are currently no effective therapies for AD. Brazilin, a natural polyphenol, inhibits Aβ fibrillogenesis, disrupts the mature fibrils and alleviates the corresponding cytotoxicity, but it also has the high toxic. Therefore, brazilin-7-2-butenoate (B-7-2-B), a brazilin derivative, was designed and synthesized. B-7-2-B exhibited lower toxicity and stronger inhibitory effect on Aβ aggregation than brazilin. B-7-2-B could prevent the formation of Aβ fibrils and oligomers, and depolymerize pre-formed aggregates in a dose-dependent manner. Furthermore, B-7-2-B prominently alleviated the cytotoxicity and the oxidative stress induced by Aβ aggregates in PC12 cells. The protective impacts of B-7-2-B were further demonstrated by using the Caenorhabditis elegans model, including decreasing the extent of Aβ aggregation, improving motility and sensation disorders. Eventually, B-7-2-B was proven to be no apparent damage to worms. In summarize, it can be concluded that B-7-2-B has the potential as a drug for treating AD.

Keywords: Aggregation; Alzheimer's disease; Amyloid β-protein

DOI: https://doi.org/10.1016/j.ijbiomac.2024.130695