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Zinc Deficiency Induces Autophagy in HT-22 Mouse Hippocampal Neuronal Cell Line

Zinc is a trace metal vital for various functions in nerve cells, although the effect of zinc deficiency on neuronal autophagy remains unclear. This study aimed to elucidate whether zinc deficiency induced by treatment with N, N, N′, N′-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), a zinc chela...

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Autores principales: Kim, Si-Yeon, Lee, Jung-Ho, Kim, Soon-Ae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9369147/
https://www.ncbi.nlm.nih.gov/pubmed/35955944
http://dx.doi.org/10.3390/ijms23158811
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author Kim, Si-Yeon
Lee, Jung-Ho
Kim, Soon-Ae
author_facet Kim, Si-Yeon
Lee, Jung-Ho
Kim, Soon-Ae
author_sort Kim, Si-Yeon
collection PubMed
description Zinc is a trace metal vital for various functions in nerve cells, although the effect of zinc deficiency on neuronal autophagy remains unclear. This study aimed to elucidate whether zinc deficiency induced by treatment with N, N, N′, N′-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), a zinc chelator, affects and alters autophagy activity. In cell viability assays, TPEN showed cytotoxicity in HT-22 cells. TPEN treatment also increased LC3-II levels and the ratio of LC3-II to LC3-I. Western blot analysis showed that phospho-AMP-activated protein kinase levels and the ratio of phospho-AMP-activated protein kinase to total AMP-activated protein kinase increased. Protein levels of the mammalian target of rapamycin and sirtuin 1 decreased following TPEN treatment. When TPEN-treated HT-22 cells were cotreated with autophagy inhibitors, 3-methyladenine (1 mM), or bafilomycin A1 (3 nM), the TPEN-induced decrease in cell viability was exacerbated. Cotreatment with chloroquine (10 μM) partially restored cell viability. The study showed that zinc deficiency induces autophagy and may be cytoprotective in neurons. We expect our results to add a new perspective to our understanding of the neuronal pathology related to zinc deficiency.
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spelling pubmed-93691472022-08-12 Zinc Deficiency Induces Autophagy in HT-22 Mouse Hippocampal Neuronal Cell Line Kim, Si-Yeon Lee, Jung-Ho Kim, Soon-Ae Int J Mol Sci Article Zinc is a trace metal vital for various functions in nerve cells, although the effect of zinc deficiency on neuronal autophagy remains unclear. This study aimed to elucidate whether zinc deficiency induced by treatment with N, N, N′, N′-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), a zinc chelator, affects and alters autophagy activity. In cell viability assays, TPEN showed cytotoxicity in HT-22 cells. TPEN treatment also increased LC3-II levels and the ratio of LC3-II to LC3-I. Western blot analysis showed that phospho-AMP-activated protein kinase levels and the ratio of phospho-AMP-activated protein kinase to total AMP-activated protein kinase increased. Protein levels of the mammalian target of rapamycin and sirtuin 1 decreased following TPEN treatment. When TPEN-treated HT-22 cells were cotreated with autophagy inhibitors, 3-methyladenine (1 mM), or bafilomycin A1 (3 nM), the TPEN-induced decrease in cell viability was exacerbated. Cotreatment with chloroquine (10 μM) partially restored cell viability. The study showed that zinc deficiency induces autophagy and may be cytoprotective in neurons. We expect our results to add a new perspective to our understanding of the neuronal pathology related to zinc deficiency. MDPI 2022-08-08 /pmc/articles/PMC9369147/ /pubmed/35955944 http://dx.doi.org/10.3390/ijms23158811 Text en © 2022 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
Kim, Si-Yeon
Lee, Jung-Ho
Kim, Soon-Ae
Zinc Deficiency Induces Autophagy in HT-22 Mouse Hippocampal Neuronal Cell Line
title Zinc Deficiency Induces Autophagy in HT-22 Mouse Hippocampal Neuronal Cell Line
title_full Zinc Deficiency Induces Autophagy in HT-22 Mouse Hippocampal Neuronal Cell Line
title_fullStr Zinc Deficiency Induces Autophagy in HT-22 Mouse Hippocampal Neuronal Cell Line
title_full_unstemmed Zinc Deficiency Induces Autophagy in HT-22 Mouse Hippocampal Neuronal Cell Line
title_short Zinc Deficiency Induces Autophagy in HT-22 Mouse Hippocampal Neuronal Cell Line
title_sort zinc deficiency induces autophagy in ht-22 mouse hippocampal neuronal cell line
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9369147/
https://www.ncbi.nlm.nih.gov/pubmed/35955944
http://dx.doi.org/10.3390/ijms23158811
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