Cargando…
Manganese-Induced Neurotoxicity through Impairment of Cross-Talk Pathways in Human Neuroblastoma Cell Line SH-SY5Y Differentiated with Retinoic Acid
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...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704659/ https://www.ncbi.nlm.nih.gov/pubmed/34941782 http://dx.doi.org/10.3390/toxics9120348 |
_version_ | 1784621759759122432 |
---|---|
author | Hernández, Raúl Bonne de Souza-Pinto, Nadja C. Kleinjans, Jos van Herwijnen, Marcel Piepers, Jolanda Moteshareie, Houman Burnside, Daniel Golshani, Ashkan |
author_facet | Hernández, Raúl Bonne de Souza-Pinto, Nadja C. Kleinjans, Jos van Herwijnen, Marcel Piepers, Jolanda Moteshareie, Houman Burnside, Daniel Golshani, Ashkan |
author_sort | Hernández, Raúl Bonne |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8704659 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87046592021-12-25 Manganese-Induced Neurotoxicity through Impairment of Cross-Talk Pathways in Human Neuroblastoma Cell Line SH-SY5Y Differentiated with Retinoic Acid Hernández, Raúl Bonne de Souza-Pinto, Nadja C. Kleinjans, Jos van Herwijnen, Marcel Piepers, Jolanda Moteshareie, Houman Burnside, Daniel Golshani, Ashkan Toxics Article 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. MDPI 2021-12-09 /pmc/articles/PMC8704659/ /pubmed/34941782 http://dx.doi.org/10.3390/toxics9120348 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Hernández, Raúl Bonne de Souza-Pinto, Nadja C. Kleinjans, Jos van Herwijnen, Marcel Piepers, Jolanda Moteshareie, Houman Burnside, Daniel Golshani, Ashkan Manganese-Induced Neurotoxicity through Impairment of Cross-Talk Pathways in Human Neuroblastoma Cell Line SH-SY5Y Differentiated with Retinoic Acid |
title | Manganese-Induced Neurotoxicity through Impairment of Cross-Talk Pathways in Human Neuroblastoma Cell Line SH-SY5Y Differentiated with Retinoic Acid |
title_full | Manganese-Induced Neurotoxicity through Impairment of Cross-Talk Pathways in Human Neuroblastoma Cell Line SH-SY5Y Differentiated with Retinoic Acid |
title_fullStr | Manganese-Induced Neurotoxicity through Impairment of Cross-Talk Pathways in Human Neuroblastoma Cell Line SH-SY5Y Differentiated with Retinoic Acid |
title_full_unstemmed | Manganese-Induced Neurotoxicity through Impairment of Cross-Talk Pathways in Human Neuroblastoma Cell Line SH-SY5Y Differentiated with Retinoic Acid |
title_short | Manganese-Induced Neurotoxicity through Impairment of Cross-Talk Pathways in Human Neuroblastoma Cell Line SH-SY5Y Differentiated with Retinoic Acid |
title_sort | manganese-induced neurotoxicity through impairment of cross-talk pathways in human neuroblastoma cell line sh-sy5y differentiated with retinoic acid |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704659/ https://www.ncbi.nlm.nih.gov/pubmed/34941782 http://dx.doi.org/10.3390/toxics9120348 |
work_keys_str_mv | AT hernandezraulbonne manganeseinducedneurotoxicitythroughimpairmentofcrosstalkpathwaysinhumanneuroblastomacelllineshsy5ydifferentiatedwithretinoicacid AT desouzapintonadjac manganeseinducedneurotoxicitythroughimpairmentofcrosstalkpathwaysinhumanneuroblastomacelllineshsy5ydifferentiatedwithretinoicacid AT kleinjansjos manganeseinducedneurotoxicitythroughimpairmentofcrosstalkpathwaysinhumanneuroblastomacelllineshsy5ydifferentiatedwithretinoicacid AT vanherwijnenmarcel manganeseinducedneurotoxicitythroughimpairmentofcrosstalkpathwaysinhumanneuroblastomacelllineshsy5ydifferentiatedwithretinoicacid AT piepersjolanda manganeseinducedneurotoxicitythroughimpairmentofcrosstalkpathwaysinhumanneuroblastomacelllineshsy5ydifferentiatedwithretinoicacid AT moteshareiehouman manganeseinducedneurotoxicitythroughimpairmentofcrosstalkpathwaysinhumanneuroblastomacelllineshsy5ydifferentiatedwithretinoicacid AT burnsidedaniel manganeseinducedneurotoxicitythroughimpairmentofcrosstalkpathwaysinhumanneuroblastomacelllineshsy5ydifferentiatedwithretinoicacid AT golshaniashkan manganeseinducedneurotoxicitythroughimpairmentofcrosstalkpathwaysinhumanneuroblastomacelllineshsy5ydifferentiatedwithretinoicacid |