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...

Descripción completa

Detalles Bibliográficos
Autores principales: Hernández, Raúl Bonne, de Souza-Pinto, Nadja C., Kleinjans, Jos, van Herwijnen, Marcel, Piepers, Jolanda, Moteshareie, Houman, Burnside, Daniel, Golshani, Ashkan
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