| Autor: |
Hernández RB; Laboratory of Bioinorganic and Environmental Toxicology-LABITA, Department of Chemistry, Federal University of São Paulo, Rua Prof. Artur Riedel, 275, Diadema 09972-270, SP, Brazil.; Department of Biology, Carleton University, 209 Nesbitt Biology Building, 1125 Colonel by Drive, Ottawa, ON K1S 5B6, Canada., de Souza-Pinto NC; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo (USP), Av. Prof. Lineu Prestes, 748, Butantã, São Paulo 05508-900, SP, Brazil., Kleinjans J; Department of Toxicogenomics, Maastricht University, Universiteitssingel 50, Room 4.112 UNS 50, 6229 ER Maastricht, The Netherlands., van Herwijnen M; Department of Toxicogenomics, Maastricht University, Universiteitssingel 50, Room 4.112 UNS 50, 6229 ER Maastricht, The Netherlands., Piepers J; Department of Toxicogenomics, Maastricht University, Universiteitssingel 50, Room 4.112 UNS 50, 6229 ER Maastricht, The Netherlands., Moteshareie H; Department of Biology, Carleton University, 209 Nesbitt Biology Building, 1125 Colonel by Drive, Ottawa, ON K1S 5B6, Canada., Burnside D; Department of Biology, Carleton University, 209 Nesbitt Biology Building, 1125 Colonel by Drive, Ottawa, ON K1S 5B6, Canada., Golshani A; Department of Biology, Carleton University, 209 Nesbitt Biology Building, 1125 Colonel by Drive, Ottawa, ON K1S 5B6, Canada. |
| Abstrakt: |
Manganese (Mn) is an important element; yet acute and/or chronic exposure to this metal has been linked to neurotoxicity and neurodegenerative illnesses such as Parkinson's disease and others via an unknown mechanism. To better understand it, we exposed a human neuroblastoma cell model ( SH-SY5Y ) to two Mn chemical species, MnCl 2 and Citrate of Mn(II) (0-2000 µM), followed by a cell viability assay, transcriptomics, and bioinformatics. Even though these cells have been chemically and genetically modified, which may limit the significance of our findings, we discovered that by using RA-differentiated cells instead of undifferentiated SH-SY5Y cell line, both chemical species induce a similar toxicity, potentially governed by disruption of protein metabolism, with some differences. The MnCl 2 altered amino acid metabolism, which affects RNA metabolism and protein synthesis. Citrate of Mn(II), however, inhibited the E3 ubiquitin ligases-target protein degradation pathway, which can lead to the buildup of damaged/unfolded proteins, consistent with histone modification. Finally, we discovered that Mn(II)-induced cytotoxicity in RA- SH-SY5Y cells shared 84 percent of the pathways involved in neurodegenerative diseases. |
