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The effect of copy number on α-synuclein’s toxicity and its protective role in Bax-induced apoptosis, in yeast

Apoptosis is a form of programmed cell death which is essential for the growth of dividing human cells whereas, in contrast, it is deleterious for post-mitotic cells such as neurons. Bax and α-synuclein are two human proteins which play a role in the induction of neuronal apoptosis in neurodegenerat...

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Autores principales: Akintade, Damilare D., Chaudhuri, Bhabatosh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468099/
https://www.ncbi.nlm.nih.gov/pubmed/32794578
http://dx.doi.org/10.1042/BSR20201912
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author Akintade, Damilare D.
Chaudhuri, Bhabatosh
author_facet Akintade, Damilare D.
Chaudhuri, Bhabatosh
author_sort Akintade, Damilare D.
collection PubMed
description Apoptosis is a form of programmed cell death which is essential for the growth of dividing human cells whereas, in contrast, it is deleterious for post-mitotic cells such as neurons. Bax and α-synuclein are two human proteins which play a role in the induction of neuronal apoptosis in neurodegenerative diseases like Alzheimer’s and Parkinson’s. Human Bax and α-synuclein also induce cell death when expressed in baker’s yeast, Saccharomyces cerevisiae. Quite unexpectedly, the human α-synuclein gene had been identified as an inhibitor of pro-apoptotic Bax using a yeast-based screen of a human hippocampal cDNA library. Plasmids were constructed with different promoters, which allow expression of wildtype and Parkinson’s disease (PD)-related mutant α-synuclein genes, from (i) multi-copy 2µ (episomal) plasmids and (ii) integrative plasmids that compel expression of genes from chromosomal sites in varying copy numbers (1–3). All α-synuclein-containing plasmids were introduced, through transformation, into a yeast strain which already contained a chromosomally integrated copy of Bax. It is for the first time that it was observed that, depending on gene dosage, only wildtype α-synuclein is anti-apoptotic while mutant α-synuclein is not. The results also indicate that wildtype α-synuclein has a remarkable ability to manifest two contrasting effects depending on its level of expression: (i) normally, it would negate apoptosis but (ii) when overexpressed, it tends to induce apoptosis which is probably what happens in PD.
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spelling pubmed-74680992020-09-11 The effect of copy number on α-synuclein’s toxicity and its protective role in Bax-induced apoptosis, in yeast Akintade, Damilare D. Chaudhuri, Bhabatosh Biosci Rep Cell Death & Injury Apoptosis is a form of programmed cell death which is essential for the growth of dividing human cells whereas, in contrast, it is deleterious for post-mitotic cells such as neurons. Bax and α-synuclein are two human proteins which play a role in the induction of neuronal apoptosis in neurodegenerative diseases like Alzheimer’s and Parkinson’s. Human Bax and α-synuclein also induce cell death when expressed in baker’s yeast, Saccharomyces cerevisiae. Quite unexpectedly, the human α-synuclein gene had been identified as an inhibitor of pro-apoptotic Bax using a yeast-based screen of a human hippocampal cDNA library. Plasmids were constructed with different promoters, which allow expression of wildtype and Parkinson’s disease (PD)-related mutant α-synuclein genes, from (i) multi-copy 2µ (episomal) plasmids and (ii) integrative plasmids that compel expression of genes from chromosomal sites in varying copy numbers (1–3). All α-synuclein-containing plasmids were introduced, through transformation, into a yeast strain which already contained a chromosomally integrated copy of Bax. It is for the first time that it was observed that, depending on gene dosage, only wildtype α-synuclein is anti-apoptotic while mutant α-synuclein is not. The results also indicate that wildtype α-synuclein has a remarkable ability to manifest two contrasting effects depending on its level of expression: (i) normally, it would negate apoptosis but (ii) when overexpressed, it tends to induce apoptosis which is probably what happens in PD. Portland Press Ltd. 2020-09-02 /pmc/articles/PMC7468099/ /pubmed/32794578 http://dx.doi.org/10.1042/BSR20201912 Text en © 2020 The Author(s). https://creativecommons.org/licenses/by/4.0/ This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).
spellingShingle Cell Death & Injury
Akintade, Damilare D.
Chaudhuri, Bhabatosh
The effect of copy number on α-synuclein’s toxicity and its protective role in Bax-induced apoptosis, in yeast
title The effect of copy number on α-synuclein’s toxicity and its protective role in Bax-induced apoptosis, in yeast
title_full The effect of copy number on α-synuclein’s toxicity and its protective role in Bax-induced apoptosis, in yeast
title_fullStr The effect of copy number on α-synuclein’s toxicity and its protective role in Bax-induced apoptosis, in yeast
title_full_unstemmed The effect of copy number on α-synuclein’s toxicity and its protective role in Bax-induced apoptosis, in yeast
title_short The effect of copy number on α-synuclein’s toxicity and its protective role in Bax-induced apoptosis, in yeast
title_sort effect of copy number on α-synuclein’s toxicity and its protective role in bax-induced apoptosis, in yeast
topic Cell Death & Injury
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468099/
https://www.ncbi.nlm.nih.gov/pubmed/32794578
http://dx.doi.org/10.1042/BSR20201912
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