International Journal of Nanomedicine (Mar 2023)
Gold Nanoparticles Reduce Food Sensation in Caenorhabditis elegans via the Voltage-Gated Channel EGL-19
Abstract
Meimei Wang,1,* Zhenzhen Zhang,2,* Ning Sun,3 Baolin Yang,4 Jihao Mo,5 Daping Wang,2 Mingqin Su,1 Jian Hu,1 Miaomiao Wang,6 Lei Wang7,8 1Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China; 2Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, 518055, People’s Republic of China; 3Institute of Clinical Laboratory Science, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, 210002, People’s Republic of China; 4Institute of Technical Biology & Agriculture Engineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230032, People’s Republic of China; 5Department of Medical Laboratory, Luoyang Orthopedic Hospital of Henan Province, Orthopedic Institute of Henan Province, Luoyang, Henan, 459001, People’s Republic of China; 6School of Medical Science, Huang He Science and Technology University, Zhengzhou, Henan, 459001, People’s Republic of China; 7School of Biological Sciences, Nanyang Technological University, Singapore, 639798, Singapore; 8Department of Physiology and Biophysics, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA*These authors contributed equally to this workCorrespondence: Lei Wang, Department of Physiology and Biophysics, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA, Tel +1 786-620-1400, Email [email protected]: The increasing use of gold nanoparticles (Au NPs) in the medical field has raised concerns about the potential adverse effect of Au NPs exposure. However, it is difficult to assess the health risks of Au NPs exposure at the individual organ level using current measurement techniques.Methods: The physical and chemical properties of Au NPs were characterized by transmission electron microscope (TEM), Fourier transform infrared (FTIR), and zeta sizer. The RNA-seq data of Au NPs-exposed worms were analyzed. The food intake was measured by liquid culture and Pharyngeal pumping rate. The function of the smell and taste neurons was evaluated by the chemotaxis and avoidance assay. The activation of ASE neurons was analyzed by calcium imaging. The gene expression of ins-22 and egl-19 was obtained from the C. elegans single cell RNA-seq databases.Results: Our data analysis indicated that 62.8% of the significantly altered genes were functional in the nervous system. Notably, developmental stage analysis demonstrated that exposure to Au NPs interfered with animal development by regulating foraging behavior. Also, our chemotaxis results showed that exposure to Au NPs reduced the sensation of C. elegans to NaCl, which was consistent with the decrease in calcium transit of ASEL. Further studies confirmed that the reduced calcium transit was dependent on voltage-gated calcium channel EGL-19. The neuropeptide INS-22 was partially involved in Au NPs-induced NaCl sensation defect. Therefore, we proposed that Au NPs reduced the calcium transit in the ASEL neuron through egl-19-dependent calcium channels. It was partially regulated by the DAF-16 targeting neuropeptide INS-22.Discussion: Our results demonstrate that Au NPs affect food sensation by reducing the calcium transit in ASEL neurons, which further leads to reduced pharynx pumping and feeding defects. The toxicology studies of Au NPs from worms have great potential to guide the usage of Au NPs in the medical field such as targeted drug delivery.Graphical Abstract: Keywords: gold nanoparticles, RNA sequencing, ASEL neuron, voltage-gated calcium channel, developmental toxicity, Caenorhabditis elegans
