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The Association of VDAC with Cell Viability of PC12 Model of Huntington’s Disease
It is becoming increasingly apparent that mitochondria dysfunction plays an important role in the pathogenesis of Huntington’s disease (HD), but the underlying mechanism is still elusive. Thus, there is a still need for further studies concerning the upstream events in the mitochondria dysfunction t...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5104952/ https://www.ncbi.nlm.nih.gov/pubmed/27891320 http://dx.doi.org/10.3389/fonc.2016.00238 |
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author | Karachitos, Andonis Grobys, Daria Kulczyńska, Klaudia Sobusiak, Adrian Kmita, Hanna |
author_facet | Karachitos, Andonis Grobys, Daria Kulczyńska, Klaudia Sobusiak, Adrian Kmita, Hanna |
author_sort | Karachitos, Andonis |
collection | PubMed |
description | It is becoming increasingly apparent that mitochondria dysfunction plays an important role in the pathogenesis of Huntington’s disease (HD), but the underlying mechanism is still elusive. Thus, there is a still need for further studies concerning the upstream events in the mitochondria dysfunction that could contribute to cell death observed in HD. Taking into account the fundamental role of the voltage-dependent anion-selective channel (VDAC) in mitochondria functioning, it is reasonable to consider the channel as a crucial element in HD etiology. Therefore, we applied inducible PC12 cell model of HD to determine the relationship between the effect of expression of wild type and mutant huntingtin (Htt and mHtt, respectively) on cell survival and mitochondria functioning in intact cells under conditions of undergoing cell divisions. Because after 48 h of Htt and mHtt expression differences in mitochondria functioning co-occurred with differences in the cell viability, we decided to estimate the effect of Htt and mHtt expression lasted for 48 h on VDAC functioning. Therefore, we isolated VDAC from the cells and tested the preparations by black lipid membrane system. We observed that the expression of mHtt, but not Htt, resulted in changes of the open state conductance and voltage-dependence when compared to control cells cultured in the absence of the expression. Importantly, for all the VDAC preparations, we observed a dominant quantitative content of VDAC1, and the quantitative relationships between VDAC isoforms were not changed by Htt and mHtt expression. Thus, Htt and mHtt-mediated functional changes of VDAC, being predominantly VDAC1, which occur shortly after these protein appearances in cells, may result in differences concerning mitochondria functioning and viability of cells expressing Htt and mHtt. The assumption is important for better understanding of cytotoxicity as well as cytoprotection mechanisms of potential clinical application. |
format | Online Article Text |
id | pubmed-5104952 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-51049522016-11-25 The Association of VDAC with Cell Viability of PC12 Model of Huntington’s Disease Karachitos, Andonis Grobys, Daria Kulczyńska, Klaudia Sobusiak, Adrian Kmita, Hanna Front Oncol Oncology It is becoming increasingly apparent that mitochondria dysfunction plays an important role in the pathogenesis of Huntington’s disease (HD), but the underlying mechanism is still elusive. Thus, there is a still need for further studies concerning the upstream events in the mitochondria dysfunction that could contribute to cell death observed in HD. Taking into account the fundamental role of the voltage-dependent anion-selective channel (VDAC) in mitochondria functioning, it is reasonable to consider the channel as a crucial element in HD etiology. Therefore, we applied inducible PC12 cell model of HD to determine the relationship between the effect of expression of wild type and mutant huntingtin (Htt and mHtt, respectively) on cell survival and mitochondria functioning in intact cells under conditions of undergoing cell divisions. Because after 48 h of Htt and mHtt expression differences in mitochondria functioning co-occurred with differences in the cell viability, we decided to estimate the effect of Htt and mHtt expression lasted for 48 h on VDAC functioning. Therefore, we isolated VDAC from the cells and tested the preparations by black lipid membrane system. We observed that the expression of mHtt, but not Htt, resulted in changes of the open state conductance and voltage-dependence when compared to control cells cultured in the absence of the expression. Importantly, for all the VDAC preparations, we observed a dominant quantitative content of VDAC1, and the quantitative relationships between VDAC isoforms were not changed by Htt and mHtt expression. Thus, Htt and mHtt-mediated functional changes of VDAC, being predominantly VDAC1, which occur shortly after these protein appearances in cells, may result in differences concerning mitochondria functioning and viability of cells expressing Htt and mHtt. The assumption is important for better understanding of cytotoxicity as well as cytoprotection mechanisms of potential clinical application. Frontiers Media S.A. 2016-11-11 /pmc/articles/PMC5104952/ /pubmed/27891320 http://dx.doi.org/10.3389/fonc.2016.00238 Text en Copyright © 2016 Karachitos, Grobys, Kulczyńska, Sobusiak and Kmita. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Karachitos, Andonis Grobys, Daria Kulczyńska, Klaudia Sobusiak, Adrian Kmita, Hanna The Association of VDAC with Cell Viability of PC12 Model of Huntington’s Disease |
title | The Association of VDAC with Cell Viability of PC12 Model of Huntington’s Disease |
title_full | The Association of VDAC with Cell Viability of PC12 Model of Huntington’s Disease |
title_fullStr | The Association of VDAC with Cell Viability of PC12 Model of Huntington’s Disease |
title_full_unstemmed | The Association of VDAC with Cell Viability of PC12 Model of Huntington’s Disease |
title_short | The Association of VDAC with Cell Viability of PC12 Model of Huntington’s Disease |
title_sort | association of vdac with cell viability of pc12 model of huntington’s disease |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5104952/ https://www.ncbi.nlm.nih.gov/pubmed/27891320 http://dx.doi.org/10.3389/fonc.2016.00238 |
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