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Aluminium Induced Endoplasmic Reticulum Stress Mediated Cell Death in SH-SY5Y Neuroblastoma Cell Line Is Independent of p53

Aluminium (Al) is the third most abundant element in the earth’s crust and its compounds are used in the form of house hold utensils, medicines and in antiperspirant etc. Increasing number of evidences suggest the involvement of Al(+3) ions in a variety of neurodegenerative disorders including Alzhe...

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Autores principales: Mustafa Rizvi, Syed Husain, Parveen, Arshiya, Verma, Anoop K., Ahmad, Iqbal, Arshad, Md, Mahdi, Abbas Ali
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039480/
https://www.ncbi.nlm.nih.gov/pubmed/24878590
http://dx.doi.org/10.1371/journal.pone.0098409
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author Mustafa Rizvi, Syed Husain
Parveen, Arshiya
Verma, Anoop K.
Ahmad, Iqbal
Arshad, Md
Mahdi, Abbas Ali
author_facet Mustafa Rizvi, Syed Husain
Parveen, Arshiya
Verma, Anoop K.
Ahmad, Iqbal
Arshad, Md
Mahdi, Abbas Ali
author_sort Mustafa Rizvi, Syed Husain
collection PubMed
description Aluminium (Al) is the third most abundant element in the earth’s crust and its compounds are used in the form of house hold utensils, medicines and in antiperspirant etc. Increasing number of evidences suggest the involvement of Al(+3) ions in a variety of neurodegenerative disorders including Alzheimer’s disease. Here, we have attempted to investigate the role of Al in endoplasmic reticulum stress and the regulation of p53 during neuronal apoptosis using neuroblastoma cell line. We observed that Al caused oxidative stress by increasing ROS production and intracellular calcium levels together with depletion of intracellular GSH levels. We also studied modulation of key pro- and anti-apoptotic proteins and found significant alterations in the levels of Nrf2, NQO1, pAKT, p21, Bax, Bcl2, Aβ1-40 and Cyt c together with increase in endoplasmic reticulum (ER) stress related proteins like CHOP and caspase 12. However, with respect to the role of p53, we observed downregulation of its transcript as well as protein levels while analysis of its ubiquitination status revealed no significant changes. Not only did Al increase the activities of caspase 9, caspase 12 and caspase 3, but, by the use of peptide inhibitors of specific and pan-caspases, we observed significant protection against neuronal cell death upon inhibition of caspase 12, demonstrating the prominent role of endoplasmic reticulum stress generated responses in Al toxicity. Overall our findings suggest that Al induces ER stress and ROS generation which compromises the antioxidant defenses of neuronal cells thereby promoting neuronal apoptosis in p53 independent pathway.
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spelling pubmed-40394802014-06-02 Aluminium Induced Endoplasmic Reticulum Stress Mediated Cell Death in SH-SY5Y Neuroblastoma Cell Line Is Independent of p53 Mustafa Rizvi, Syed Husain Parveen, Arshiya Verma, Anoop K. Ahmad, Iqbal Arshad, Md Mahdi, Abbas Ali PLoS One Research Article Aluminium (Al) is the third most abundant element in the earth’s crust and its compounds are used in the form of house hold utensils, medicines and in antiperspirant etc. Increasing number of evidences suggest the involvement of Al(+3) ions in a variety of neurodegenerative disorders including Alzheimer’s disease. Here, we have attempted to investigate the role of Al in endoplasmic reticulum stress and the regulation of p53 during neuronal apoptosis using neuroblastoma cell line. We observed that Al caused oxidative stress by increasing ROS production and intracellular calcium levels together with depletion of intracellular GSH levels. We also studied modulation of key pro- and anti-apoptotic proteins and found significant alterations in the levels of Nrf2, NQO1, pAKT, p21, Bax, Bcl2, Aβ1-40 and Cyt c together with increase in endoplasmic reticulum (ER) stress related proteins like CHOP and caspase 12. However, with respect to the role of p53, we observed downregulation of its transcript as well as protein levels while analysis of its ubiquitination status revealed no significant changes. Not only did Al increase the activities of caspase 9, caspase 12 and caspase 3, but, by the use of peptide inhibitors of specific and pan-caspases, we observed significant protection against neuronal cell death upon inhibition of caspase 12, demonstrating the prominent role of endoplasmic reticulum stress generated responses in Al toxicity. Overall our findings suggest that Al induces ER stress and ROS generation which compromises the antioxidant defenses of neuronal cells thereby promoting neuronal apoptosis in p53 independent pathway. Public Library of Science 2014-05-30 /pmc/articles/PMC4039480/ /pubmed/24878590 http://dx.doi.org/10.1371/journal.pone.0098409 Text en © 2014 Mustafa Rizvi et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Mustafa Rizvi, Syed Husain
Parveen, Arshiya
Verma, Anoop K.
Ahmad, Iqbal
Arshad, Md
Mahdi, Abbas Ali
Aluminium Induced Endoplasmic Reticulum Stress Mediated Cell Death in SH-SY5Y Neuroblastoma Cell Line Is Independent of p53
title Aluminium Induced Endoplasmic Reticulum Stress Mediated Cell Death in SH-SY5Y Neuroblastoma Cell Line Is Independent of p53
title_full Aluminium Induced Endoplasmic Reticulum Stress Mediated Cell Death in SH-SY5Y Neuroblastoma Cell Line Is Independent of p53
title_fullStr Aluminium Induced Endoplasmic Reticulum Stress Mediated Cell Death in SH-SY5Y Neuroblastoma Cell Line Is Independent of p53
title_full_unstemmed Aluminium Induced Endoplasmic Reticulum Stress Mediated Cell Death in SH-SY5Y Neuroblastoma Cell Line Is Independent of p53
title_short Aluminium Induced Endoplasmic Reticulum Stress Mediated Cell Death in SH-SY5Y Neuroblastoma Cell Line Is Independent of p53
title_sort aluminium induced endoplasmic reticulum stress mediated cell death in sh-sy5y neuroblastoma cell line is independent of p53
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039480/
https://www.ncbi.nlm.nih.gov/pubmed/24878590
http://dx.doi.org/10.1371/journal.pone.0098409
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