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MiRNA-210 modulates a nickel-induced cellular energy metabolism shift by repressing the iron–sulfur cluster assembly proteins ISCU1/2 in Neuro-2a cells
The cellular energy metabolism shift, characterized by the inhibition of oxidative phosphorylation (OXPHOS) and enhancement of glycolysis, is involved in nickel-induced neurotoxicity. MicroRNA-210 (miR-210) is regulated by hypoxia-inducible transcription factor-1α (HIF-1α) under hypoxic conditions a...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944272/ https://www.ncbi.nlm.nih.gov/pubmed/24577088 http://dx.doi.org/10.1038/cddis.2014.60 |
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author | He, M Lu, Y Xu, S Mao, L Zhang, L Duan, W Liu, C Pi, H Zhang, Y Zhong, M Yu, Z Zhou, Z |
author_facet | He, M Lu, Y Xu, S Mao, L Zhang, L Duan, W Liu, C Pi, H Zhang, Y Zhong, M Yu, Z Zhou, Z |
author_sort | He, M |
collection | PubMed |
description | The cellular energy metabolism shift, characterized by the inhibition of oxidative phosphorylation (OXPHOS) and enhancement of glycolysis, is involved in nickel-induced neurotoxicity. MicroRNA-210 (miR-210) is regulated by hypoxia-inducible transcription factor-1α (HIF-1α) under hypoxic conditions and controls mitochondrial energy metabolism by repressing the iron–sulfur cluster assembly protein (ISCU1/2). ISCU1/2 facilitates the assembly of iron–sulfur clusters (ISCs), the prosthetic groups that are critical for mitochondrial oxidation-reduction reactions. This study aimed to investigate whether miR-210 modulates alterations in energy metabolism after nickel exposure through suppressing ISCU1/2 and inactivating ISCs-containing metabolic enzymes. We determined that NiCl(2) exposure leads to a significant accumulation of HIF-1α, rather than HIF-1β, in Neuro-2a cells. The miR-210 overexpression and ISCU1/2 downregulation was observed in a dose- and time-dependent manner. The gain-of-function and loss-of-dysfunction assays revealed that miR-210 mediated the ISCU1/2 suppression, energy metabolism alterations, and ISC-containing metabolic enzyme inactivation after nickel exposure. In addition, the impact of miR-210 on ISC-containing metabolic enzymes was independent from cellular iron regulation. Overall, these data suggest that repression of miR-210 on ISCU1/2 may contribute to HIF-1α-triggered alterations in energy metabolism after nickel exposure. A better understanding of how nickel impacts cellular energy metabolism may facilitate the elucidation of the mechanisms by which nickel affects the human health. |
format | Online Article Text |
id | pubmed-3944272 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-39442722014-03-06 MiRNA-210 modulates a nickel-induced cellular energy metabolism shift by repressing the iron–sulfur cluster assembly proteins ISCU1/2 in Neuro-2a cells He, M Lu, Y Xu, S Mao, L Zhang, L Duan, W Liu, C Pi, H Zhang, Y Zhong, M Yu, Z Zhou, Z Cell Death Dis Original Article The cellular energy metabolism shift, characterized by the inhibition of oxidative phosphorylation (OXPHOS) and enhancement of glycolysis, is involved in nickel-induced neurotoxicity. MicroRNA-210 (miR-210) is regulated by hypoxia-inducible transcription factor-1α (HIF-1α) under hypoxic conditions and controls mitochondrial energy metabolism by repressing the iron–sulfur cluster assembly protein (ISCU1/2). ISCU1/2 facilitates the assembly of iron–sulfur clusters (ISCs), the prosthetic groups that are critical for mitochondrial oxidation-reduction reactions. This study aimed to investigate whether miR-210 modulates alterations in energy metabolism after nickel exposure through suppressing ISCU1/2 and inactivating ISCs-containing metabolic enzymes. We determined that NiCl(2) exposure leads to a significant accumulation of HIF-1α, rather than HIF-1β, in Neuro-2a cells. The miR-210 overexpression and ISCU1/2 downregulation was observed in a dose- and time-dependent manner. The gain-of-function and loss-of-dysfunction assays revealed that miR-210 mediated the ISCU1/2 suppression, energy metabolism alterations, and ISC-containing metabolic enzyme inactivation after nickel exposure. In addition, the impact of miR-210 on ISC-containing metabolic enzymes was independent from cellular iron regulation. Overall, these data suggest that repression of miR-210 on ISCU1/2 may contribute to HIF-1α-triggered alterations in energy metabolism after nickel exposure. A better understanding of how nickel impacts cellular energy metabolism may facilitate the elucidation of the mechanisms by which nickel affects the human health. Nature Publishing Group 2014-02 2014-02-27 /pmc/articles/PMC3944272/ /pubmed/24577088 http://dx.doi.org/10.1038/cddis.2014.60 Text en Copyright © 2014 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ |
spellingShingle | Original Article He, M Lu, Y Xu, S Mao, L Zhang, L Duan, W Liu, C Pi, H Zhang, Y Zhong, M Yu, Z Zhou, Z MiRNA-210 modulates a nickel-induced cellular energy metabolism shift by repressing the iron–sulfur cluster assembly proteins ISCU1/2 in Neuro-2a cells |
title | MiRNA-210 modulates a nickel-induced cellular energy metabolism shift by repressing the iron–sulfur cluster assembly proteins ISCU1/2 in Neuro-2a cells |
title_full | MiRNA-210 modulates a nickel-induced cellular energy metabolism shift by repressing the iron–sulfur cluster assembly proteins ISCU1/2 in Neuro-2a cells |
title_fullStr | MiRNA-210 modulates a nickel-induced cellular energy metabolism shift by repressing the iron–sulfur cluster assembly proteins ISCU1/2 in Neuro-2a cells |
title_full_unstemmed | MiRNA-210 modulates a nickel-induced cellular energy metabolism shift by repressing the iron–sulfur cluster assembly proteins ISCU1/2 in Neuro-2a cells |
title_short | MiRNA-210 modulates a nickel-induced cellular energy metabolism shift by repressing the iron–sulfur cluster assembly proteins ISCU1/2 in Neuro-2a cells |
title_sort | mirna-210 modulates a nickel-induced cellular energy metabolism shift by repressing the iron–sulfur cluster assembly proteins iscu1/2 in neuro-2a cells |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944272/ https://www.ncbi.nlm.nih.gov/pubmed/24577088 http://dx.doi.org/10.1038/cddis.2014.60 |
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